Specificity of B-Type Natriuretic Peptide Assays: Cross-Reactivity with Different BNP, NT-proBNP, and proBNP Peptides.

BACKGROUND: B-type natriuretic peptides (BNPs) are used clinically to diagnose and monitor heart failure and are present in the circulation as multiple proBNP-derived fragments. We investigated the specificity of BNP immunoassays with glycosylated and nonglycosylated BNP, N-terminal proBNP (NT-proBNP), and proBNP peptides to probe the cross-reactivity of each assay. METHODS: Nine B-type natriuretic peptides were studied,including synthetic and recombinant BNP (Shionogi, Scios, Mayo), human and synthetic glycosylated and nonglycosylated NT-proBNP (HyTest, Roche Diagnostics), and human glycosylated and nonglycosylated proBNP (HyTest, Scios). Five BNP [Abbott, Abbott POC, Alere, Beckman Coulter, Siemens (Centaur)], 9 NT-proBNP [Ortho-Clinical Diagnostics, Roche, Response, bioMerieux, Siemens (Dimension, Immulite, Stratus CS), Mitsubishi] and 3 research-use-only proBNP immunoassays [Biosite (Alere), Bio-Rad, Goetze] were evaluated. Specificity was assessed by calculating the recovery between baseline and peptide-spiked human plasma pools at target concentrations of 100 ng/L BNP, 300 ng/L proBNP, or 450 ng/L NT-proBNP. All assays were performed in duplicate. RESULTS: BNP and NT-proBNP assays demonstrated substantial cross-reactivity with proBNP peptides. NT-proBNP assays do not detect glycosylated forms of either NT-proBNP or proBNP. proBNP assays preferentially detect the BNP 1-32 peptide and have minimal cross-reactivity with BNP peptides and glycosylated proBNP. CONCLUSIONS: BNP or NT-proBNP results are not transferable among the current existing immunoassays owing to their differences in cross-reactivity and ability to detect various glycosylated forms of proBNP-derived fragments. Opportunities remain to standardize and harmonize BNP and NT-proBNP assays, as well as to develop specific proBNP assays, to widen their clinical scope of use.

Incidence of Undetectable, Measurable, and Increased Cardiac Troponin I Concentrations Above the 99th Percentile Using a High-Sensitivity vs a Contemporary Assay in Patients Presenting to the Emergency Department.

INTRODUCTION: We compared the incidence of undetectable [below the limit of detection (LoD)], measurable (LoD to 99th percentile), and increased cardiac troponin I (cTnI) concentrations above the 99th percentile between Abbott high-sensitivity cTnI (hs-cTnI) and contemporary cTnI assays in a US emergency department population. METHODS: Patients (n = 2100) presenting to the emergency department who had serial cTnI (0, 3, 6, 9 h) measurements ordered on clinical indication were enrolled. Contemporary cTnI [Abbott Architect used clinically; 99th percentile: 0.030 µg/L (30 ng/L)] and hs-cTnI [Abbott investigational; sex-specific 99th percentiles: female (F) 16 ng/L, male (M) 34 ng/L] assays simultaneously measured fresh EDTA plasma. RESULTS: The hs-cTnI assay measured fewer undetectable cTnI concentrations compared to the contemporary cTnI assay across baseline (F: 31% vs 47%, M: 22% vs 40%) and serial (F: 21% vs 46%; M: 19% vs 54%) measurements. Conversely, the proportion of measurable cTnI concentrations was higher using hs-cTnI compared to contemporary cTnI assay across both baseline (F: 46% vs 31%; M: 60% vs 33%) and serial (F: 48% vs 28%; M: 83% vs 40%) measurements. The overall proportion of patients with increased cTnI concentrations above the 99th percentile was not significantly different between the contemporary (31%) and hs-cTnI (26%) assays (P = 0.09). CONCLUSIONS: In patients presenting to the emergency department, the use of the Abbott hs-cTnI assay provides clinicians with more numeric cTnI concentrations. This occurs via a shift from results below the LoD to those between the LoD and the 99th percentile and does not increase in the number of cTnI concentrations above the 99th percentile.

Prognostic Value of Serial Changes in High-Sensitivity Cardiac Troponin I and T over 3 Months Using Reference Change Values in Hemodialysis Patients.

INTRODUCTION: Serial changes in cardiac troponin in hemodialysis (HD) patients have uncertain clinical implications. We evaluated associations of adverse outcomes in HD patients with reference change value (RCV) data and tertile concentrations for cardiac troponin I (cTnI) and cTnT measured by high-sensitivity (hs) assays. METHODS: RCV data and tertiles for hs-cTnI and hs-cTnT were determined from plasma samples collected 3 months apart in 677 stable outpatient HD patients and assessed for their associations with adverse outcomes using adjusted Cox models. Primary outcomes were all-cause mortality and sudden cardiac death (SCD). RESULTS: During a median follow-up of 23 months, 18.6% of patients died. RCVs were: hs-cTnI +37% and -30%; hs-cTnT +25% and -20%. Patients with serial hs-cTnI and hs-cTnT changes >RCV (increase or decrease) had all-cause mortality of 25.2% and 23.8% respectively, compared to 15.0% and 16.5% with changes ≤RCV [adjusted hazard ratios (aHRs): 1.9, P = 0.0003 and 1.7, P = 0.0066), respectively]. Only hs-cTnI changes >RCV were predictive of SCD (aHR 2.6, P = 0.005). hs-Cardiac troponin changes >RCV improved all-cause mortality prognostication compared to changes ≤RCV in tertile 2: hs-cTnI aHR, 2.70 (P = 0.003); hs-cTnT aHR, 1.98 (P = 0.043). The aHR of changes in hs-cTnI in tertile 2 >RCV for SCD was 5.62 (P = 0.039). CONCLUSIONS: Changes over 3 months in hs-cTnI and hs-cTnT of >RCV identified patients at greater risk of all-cause mortality, and for hs-cTnI were also predictive of SCD. Among patients with middle tertile cardiac troponin concentrations, hs-cTnI changes >RCV provided additive prognostic value for both SCD and all-cause mortality, whereas those for hs-cTnT provided additive prognostic value only for all-cause mortality.

Determination of 19 cardiac troponin I and T assay 99th percentile values from a common presumably healthy population.

BACKGROUND: Between-assay comparability of 99th percentiles for cardiac troponin concentrations has not been assessed systematically in a single population for a large number of assays. METHODS: We determined 99th percentiles for 19 cardiac troponin assays in heparin plasma samples from a population of 272 and 252 presumably healthy males and females, respectively. The assays evaluated included 1 cardiac troponin T (cTnT) assay from Roche and 18 cTnI assays from Abbott, Alere, Beckman, bioMerieux, Instrumentation Laboratory, Ortho-Clinical Diagnostics, Singulex, Siemens, and Roche. Five of these assays were categorized as high-sensitivity, 9 as sensitive-contemporary, and 5 as point-of-care (POC) assays. RESULTS: For high-sensitivity cTnI (hs-cTnI) assays 99th percentiles varied from 23 to 58 ng/L. At least 80% of individuals had measurable hs-cTnI, whereas only 25% had measurable high-sensitivity cTnT. All high-sensitivity cardic troponin assays had 99th percentiles that were 1.2-2.4-fold higher in males than females. For the 9 sensitive-contemporary cTnI assays, 99th percentiles varied from 12 to 392 ng/L, and only the Beckman assay gave measurable concentrations in a substantial portion of the population (35% vs ≤6% for the others). Seven of these 9 assays had 1.3-5.0-fold higher 99th percentiles for males than females. For 5 cTnI POC assays, 99th percentiles varied from <10 to 40 ng/L. The Instrumentation Laboratory assay gave measurable results in 27.8% of study participants vs ≤6% for the others. Correlations were generally poor among assays. CONCLUSIONS: Among cardiac troponin assays 99th percentile concentrations appear to differ. High-sensitivity assays provide measurable cardiac troponin results in a substantially greater fraction of presumably healthy individuals.

Myeloperoxidase improves risk stratification in patients with ischemia and normal cardiac troponin I concentrations.

BACKGROUND: We assessed the ability of myeloperoxidase (MPO) to identify the risk for major adverse cardiac events (MACE) in patients who present with ischemic symptoms suggestive of acute coronary syndrome and have a normal cardiac troponin I (cTnI) value. METHODS: We used Siemens (n = 400) and Abbott (n = 350) assays to measure MPO and cTnI in plasma samples from 400 patients. Event rates (myocardial infarction, cardiac death, percutaneous coronary intervention, coronary artery bypass grafting) were estimated by the Kaplan-Meier method and compared with the log-rank statistic. RESULTS: At the 30-day follow-up, the adjusted hazard ratios for MACE were 3.9 (P < 0.001) for increased cTnI and 2.7 (P = 0.006) for increased MPO for the Siemens assays and were 5.5 (P < 0.001) for increased cTnI and 2.9 (P = 0.001) for increased MPO for the Abbott assays. Similar findings were observed with 6 months of follow-up. Patients who initially had a normal cTnI value and an increased Siemens MPO value demonstrated a higher rate of MACE at 30 days than those in whom both values were normal (16.1% vs 3.6%, P = 0.002) and 6 months (18.1% vs 5.0%, P = 0.002). Similarly, patients who had an increased Abbott MPO result demonstrated a higher MACE rate at 30 days (12.3% vs 3.9%, P = 0.03) and at 6 months (16.2% vs 5.1%, P = 0.01) than those with normal values. CONCLUSIONS: A combination of MPO and cTnI allowed the identification of a greater proportion of patients at risk for MACE than the use of cTnI alone. Increased MPO values remained predictive of future cardiac events even when the cTnI value was normal.

Analytical characteristics of commercial cardiac troponin I and T immunoassays in serum from rats, dogs, and monkeys with induced acute myocardial injury.

BACKGROUND: Information is needed regarding analytical characteristics of cardiac troponin (cTn) assays used in preclinical studies. METHODS: We measured cTnI and cTnT in serum from normal animals and animals with induced myocardial injury [Sprague-Dawley (SD) and Wistar rats, beagle dogs, and rhesus (Rh) and cynomolgus (Cy) monkeys]. We evaluated the following assays: for cTnI, Abbott Architect, Bayer Centaur (first and second generation), Beckman Access, DPC Immulite, Dade Dimension, Ortho Vitros ES, Tosoh AIA, and species-specific enzyme immunoassays; for cTnT, Roche Elecsys. RESULTS: We found different species-specific responses for the troponin assays evaluated. Abbott, Bayer Ultra, Beckman, and Dade assays gave good responses across all species. In rats, weak responses were observed with DPC and Ortho, and no measurable response with Tosoh. In dogs, weak responses were observed with Tosoh cTnI, Roche cTnT, and species-specific cTnI. In cynomolgus monkeys, weak responses were observed with species-specific cTnI and Roche cTnT. Assay imprecision was < or = 20% at 3 or more examined cTn concentrations for Beckman (rat, dog, monkey), Dade (rat, dog, monkey), Abbott (rat, dog, monkey), Bayer first generation (dog), Bayer Ultra (rat, dog, monkey), Roche (monkey), DPC (dog, monkey), Ortho (dog, monkey), and Tosoh (dog, monkey) assays, whereas imprecision was < or = 20% at 2 or fewer concentrations for the Bayer first generation (rat, monkey), Roche cTnT (rat, dog), and DPC (rat) assays. CONCLUSIONS: Not all cTn assays are suitable for monitoring cTn in each animal species or strain. Individual assay characterization by animal species is needed to prevent misinterpretation of myocardial injury-based cardiac troponin findings.

Performance characteristics of the Architect brain natriuretic peptide (BNP) assay: a two site study.

INTRODUCTION: Brain natriuretic peptide (BNP) is produced by the ventricles of the heart and is a biomarker for heart failure. Several commercial assays are now available. We evaluated the performance characteristics of the ARCHITECT BNP assay. METHODS: We evaluated the limit of blank, limit of detection, linearity and imprecision. Method comparison studies were performed with 3 other automated BNP assays including the ADVIA Centaur, AxSYM, and UniCel DxI 800 methods. RESULTS: The mean LOB and LOD of the Architect assay were 3.5 and 5.8 ng/L, respectively. Imprecision studies yielded within run CVs of 1.1 to 5.1% and total CVs of 2.3 to 5.3% using human plasma based multi-constituent controls at concentrations of 92, 500, and 3500 ng/L. The maximum deviation from the target recovery for dilution linearity was 9.6%. Concordance with other BNP assays at a 100 ng/l cutoff was 91 to 98% and kappa statistics were 0.78 to 0.96. The mean difference between the Architect and Advia Centaur methods was positive. For the other methods, the mean difference with the Architect was negative. CONCLUSIONS: The Architect BNP assay shows good performance characteristics with total imprecision < or =5.3%. It agrees well with the Advia Centaur, AxSYM, and UniCel DxI BNP assays.

Use of the bioMérieux VIDAS troponin I ultra assay for the diagnosis of myocardial infarction and detection of adverse events in patients presenting with symptoms suggestive of acute coronary syndrome.

BACKGROUND: We demonstrate the performance of the bioMérieux VIDAS Troponin I Ultra assay for diagnostic accuracy for detection of myocardial infarction (MI) and risk stratification. METHOD: cTnI was measured in 545 patients from 2 clinical centers with symptoms suggestive of ACS at admission, with an additional specimen at 4-12 h (453 patients). The 99th percentile value (0.01 microg/l) was used to assess clinical accuracy for diagnosis of acute MI. Primary endpoint for risk stratification was first of cardiac event or death in 302 patients (one center) followed for 60 days. RESULTS: 157 (28.8%) patients ruled in for an MI during index hospitalization. Sensitivities and specificities were 88.1% (95% CI 81.9 to 92.4%) and 79.9% (CI 75.5 to 83.6%) for baseline and 100% (CI 96.5 to 100%) and 79.4% (CI 74.4 to 83.4%) for follow-up specimens. ROC curve areas increased from 0.912 (CI 0.879 to 0.944) at baseline to 0.994 (CI 0.988 to 0.999) at second sampling (n=453, p<0.01); with no differences between sites. Primary endpoint rate for the 223 patients (74%) with normal cTnI on presentation was lower than the 79 patients (26%) with cTnI>0.01 ug/l (5.9% vs. 42.3%, p<0.0001). The relative risk for the >0.01 ug/l group was 8.9 (CI 4.6 to 17). CONCLUSION: The VIDAS cTnI assay is a sensitive diagnostic method for the early detection of MI and predicts increased risk for adverse events in patients with symptoms suggestive of ACS.

Sex-specific 99th percentiles derived from the AACC Universal Sample Bank for the Roche Gen 5 cTnT assay: Comorbidities and statistical methods influence derivation of reference limits.

OBJECTIVES: Our purpose was to determine a) overall and sex-specific 99th percentile upper reference limits (URL) and b) influences of statistical methods and comorbidities on the URLs. METHODS: Heparin plasma from 838 normal subjects (423 men, 415 women) were obtained from the AACC (Universal Sample Bank). The cobas e602 measured cTnT (Roche Gen 5 assay); limit of detection (LoD), 3ng/L. Hemoglobin A1c (URL 6.5%), NT-proBNP (URL 125ng/L) and eGFR (60mL/min/1.73m2) were measured, along with identification of statin use, to better define normality. 99th percentile URLs were determined by the non-parametric (NP), Harrell-Davis Estimator (HDE) and Robust (R) methods. RESULTS: 355 men and 339 women remained after exclusions. Overall<50% of subjects had measureable concentrations ≥ LoD: 45.6% no exclusion, 43.5% after exclusion; compared to men: 68.1% no exclusion, 65.1% post exclusion; women: 22.7% no exclusion, 20.9% post exclusion. The statistical method used influenced URLs as follows: pre/post exclusion overall, NP 16/16ng/L, HDE 17/17ng/L, R not available; men NP 18/16ng/L, HDE 21/19ng/L, R 16/11ng/L; women NP 13/10ng/L, HDE 14/14ng/L, R not available. CONCLUSIONS: We demonstrated that a) the Gen 5 cTnT assay does not meet the IFCC guideline for high-sensitivity assays, b) surrogate biomarkers significantly lowers the URLs and c) statistical methods used impact URLs. Our data suggest lower sex-specific cTnT 99th percentiles than reported in the FDA approved package insert. We emphasize the importance of detailing the criteria used to include and exclude subjects for defining a healthy population and the statistical method used to calculate 99th percentiles and identify outliers.

Searching for a BNP standard: Glycosylated proBNP as a common calibrator enables improved comparability of commercial BNP immunoassays.

BACKGROUND: Circulating B-type natriuretic peptide (BNP) is widely accepted as a diagnostic and risk assessment biomarker of cardiac function. Studies suggest that there are significant differences in measured concentrations among different commercial BNP immunoassays. The purpose of our study was to compare BNP-related proteins to determine a form that could be used as a common calibrator to improve the comparability of commercial BNP immunoassay results. METHODS: BNP was measured in 40 EDTA-plasma samples from acute and chronic heart failure patients using five commercial BNP assays: Alere Triage, Siemens Centaur XP, Abbott I-STAT, Beckman Access2 and ET Healthcare Pylon. In parallel with internal calibrators from each manufacturer, six preparations containing BNP 1-32 motif a) synthetic BNP, b) recombinant BNP (E. coli), c) recombinant nonglycosylated proBNP (E. coli), d) recombinant His-tagged (N-terminal) nonglycosylated proBNP (E. coli), e) recombinant glycosylated proBNP (HEK cells), and f) recombinant glycosylated proBNP (CHO cells) were also used as external calibrators for each assay. RESULTS: Using the internal standards provided by manufacturers and for five of six external calibrators, up to 3.6-fold differences (mean 1.9-fold) were observed between BNP immunoassays (mean between-assay CV 24.5-47.2%). A marked reduction of the between-assay variability was achieved, when glycosylated proBNP expressed in HEK cells was used as the common calibrator for all assays (mean between-assay CV 14.8%). CONCLUSIONS: Our data suggest that recombinant glycosylated proBNP could serve as a common calibrator for BNP immunoassays to reduce between-assay variability and achieve better comparability of BNP concentrations of commercial BNP immunoassays.

Performance characteristics of the ARCHITECT Galectin-3 assay.

OBJECTIVES: Galectin-3 is an emerging biomarker that is commonly increased in patients with heart failure and/or patients at risk for cardiovascular disease. We evaluated the Galectin-3 assay on the Abbott ARCHITECT i1000(SR) and ARCHITECT i2000(SR) at 2 testing sites. DESIGN AND METHODS: Imprecision (%CV), interference, limits of blank (LoB), detection (LoD), and quantitation (LoQ), linearity, method comparison to an ELISA method, comparisons between plasma and serum, and reference intervals were evaluated. Imprecision was performed based on two runs of duplicate testing conducted daily. Verification of LoB, LoD, and LoQ was performed according to Clinical and Laboratory Standards Institute guidelines. Linearity was evaluated by making 5 dilutions of a high patient EDTA plasma pool with a low patient pool. Reference intervals were established using EDTA plasma collected from self-reported healthy volunteers. A second lot of reagent was used at one site for method comparison and imprecision studies. RESULTS: Total CV's were ≤6.0%. A positive interference was observed for hemolyzed samples over 2.0 g/L hemolysate. The LoB ranged from 0.1 to 0.3 ng/mL, the LoD from 1.4 to 2.1 ng/mL and the LoQ from 3.0 to 3.3 ng/mL. Linearity studies had slopes and correlation coefficients equal to 1.0. Comparison of the i1000(SR) and i2000(SR) to the ELISA method demonstrated slopes of 1.0 to 1.2 and correlation coefficients of 0.93 to 0.97. The 97.5th percentile of the reference interval was 18.7 and 17.9 ng/mL for the i1000(SR) and i2000(SR), respectively. CONCLUSIONS: The Abbott Galectin-3 assay demonstrated acceptable analytical performance on both the ARCHITECT i1000(SR) and ARCHITECT i2000(SR).

Use of the Centaur TnI-Ultra assay for detection of myocardial infarction and adverse events in patients presenting with symptoms suggestive of acute coronary syndrome.

BACKGROUND: We determined the diagnostic accuracy of the Advia Centaur TnI-Ultra assay for detecting myocardial infarction (MI) and assessing risk of adverse events in patients presenting with ischemic symptoms suggestive of acute coronary syndrome. METHODS: We measured cardiac troponin I (cTnI) on admission and 6-24 h after admission (follow-up) in plasma specimens from 371 consecutive patients. The end point was the first of cardiac event or death within 60 days. We estimated survival curves using the Kaplan-Meier method and compared groups with the log rank statistic. RESULTS: MI was established in 49 patients (13%). Clinical sensitivities and specificities for MI based on the 99th percentile (0.04 microg/L) were 74% and 84%, respectively, on admission and 94% and 81% at follow-up. ROC curves showed significantly higher accuracy for MI in the follow-up specimen compared with admission (P = 0.001). Overall there were 2 cardiac deaths, 1 noncardiac death, 49 MIs, 7 coronary artery bypass grafts, and 36 percutaneous coronary interventions in 59 patients during follow-up. The event rate in those with cTnI <0.006 microg/L was significantly lower than in groups with cTnI 0.006-0.04 microg/L, >0.04-0.10 microg/L, or >0.10 microg/L (2.8% vs 11.1%, 24.1%, 55.1%, respectively; P <0.0001). Relative risks for the increasing cTnI cutoff groups were 3.9 (95% CI 1.2-13), 8.9 (2.4-34), and 25 (7.3-82) after adjustment for age, diabetes, history of hypertension, previous MI, and estimated glomerular filtration rate. CONCLUSIONS: The TnI-Ultra assay is a sensitive, early diagnostic biomarker for MI and an independent predictor of adverse events at any measurable cTnI in patients with symptoms of acute coronary syndrome.

Multiple biomarker use for detection of adverse events in patients presenting with symptoms suggestive of acute coronary syndrome.

BACKGROUND: We investigated multiple biomarkers of various pathophysiologic pathways to determine their relationships with adverse outcomes in patients presenting with symptoms of acute coronary syndrome. METHODS: We obtained plasma specimens from 457 patients on admission and measured 7 biomarkers: myeloperoxidase (MPO), soluble CD40 ligand (CD40L), placental growth factor (PlGF), metalloproteinase-9 (MMP-9), high-sensitivity C-reactive protein (hsCRP), cardiac troponin I (cTnI), and N-terminal pro-B-type natriuretic peptide (NT-proBNP). We used the Modification of Diet in Renal Disease formula to calculate the estimated glomerular filtration rate (eGFR). Endpoints were cardiac events (myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft, cardiac death) and all-cause mortality. We estimated cumulative event rates over a 4-month period with the Kaplan-Meier method and relative risk (RR) with the Cox proportional hazards model. RESULTS: Patients with increased PlGF, NT-proBNP, hsCRP, or cTnI or decreased eGFR had 11% to 20% higher all-cause mortality rates than patients with concentrations within reference intervals: 20.4% (eGFR), 16.0% (PlGF), 15.8% (hsCRP), 12.7% (NT-proBNP), and 11.3% (cTnI; all P < or = 0.03). No differences in mortality rates were observed between those with increased vs normal concentrations of MPO, CD40L, or MMP-9. Decreased eGFR (RR 3.4, P = 0.004) and increased NT-proBNP (RR 7.9, P = 0.04) were independently predictive of mortality, and PlGF (RR 2.0, P = 0.08) approached significance. Patients with increased NT-proBNP (12.3%) or cTnI (33.8%) had higher cardiac event rates (each P <0.02), with increased MPO (11.1%) showing a trend (P = 0.09). Patients in whom both cTnI and MPO were increased had a cardiac event rate of 43%. CONCLUSION: Multiple biomarkers that are likely indicative of different underlying pathophysiologic mechanisms are independently predictive of increased risk for adverse events in patients with acute coronary syndrome.

Point-of-care i-STAT cardiac troponin I for assessment of patients with symptoms suggestive of acute coronary syndrome.

BACKGROUND: Few studies have investigated the role of cardiac troponin point-of-care (POC) testing for predicting adverse outcomes in acute coronary syndrome (ACS) patients. We investigated the use of a POC cTnI assay in ACS patients. METHODS: We studied consecutive patients (n = 367) presenting with symptoms suggestive of ACS who were admitted through the emergency department. We measured plasma cTnI with the i-STAT assay. Patients were risk-stratified based on cTnI concentrations defined by the predetermined 99th percentile reference limit for plasma (0.04 microg/L). Patients were followed for 60 days. We computed survival and event curves with the Kaplan-Meier method and compared risk stratification groups with the log-rank test. RESULTS: Acute myocardial infarction (MI) was diagnosed in 8.1% of patients. Odds ratios and 95% confidence intervals for all-cause death (ACD), MI or ACD, MI or cardiac death, and cardiac death at 60 days were all statistically significant after adjustment for age, diabetes, hypertension, and history of renal failure as follows: 2.54 (1.24-5.20), P = 0.009; 2.76 (1.37-5.58), P = 0.003; 5.98 (1.65-21.7), P = 0.008; and 2.54 (1.24-5.20), P = 0.009. Kaplan-Meier curves showed early separation between patients with increased vs. reference concentrations before 30 days for ACD, MI or ACD, and MI or cardiac death. CONCLUSION: The i-STAT POC cTnI assay can be added to the list of assays for risk stratification.