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Introduction: This study examined the analytical performance of a whole blood (WB) point of care (POC) hs-cTnI assay compared to a plasma central laboratory hs-cTnI assay in patients presenting with ischemic symptoms to a US emergency department., Methods: Fresh WB specimens collected at 0 and 2 h from 1089 consecutive patients (2152 total from 1076 matched specimens) were analyzed for hs-cTnI using WB on POC Siemens Atellica VTLi assay and plasma on central laboratory Siemens Atellica IM assay. Concordances were determined based on concentrations ranging from < limit of detection (LoD), LoD to overall and sex specific 99th percentiles from both the IFCC manufacturer package inserts and Universal Sample Bank (USB) data, and > 99th percentiles. Method comparisons were calculated using Passing Bablok regression and Bland Altmann plots, and linear regression determined by Pearson correlation coefficient., Results: Baseline concentration comparisons showed: POC VTLi < LoD 4-5 %, ≥ LoD 95 %; Atellica IM < LoD 5-7 %, and ≥ LoD 94-95 %. From the 2152 paired 0 and 2-hour samples, based on 99th percentiles, overall concordance was 91-92 % (kappa 0.72-0.77) and discordance 8 %. Passing Bablok regression analysis using 1924 specimens between LoD to 500 ng/L showed: slopes 0.469-0.490; y-intercepts 1.753-2.028; r values 0.631-0.817. Pearson correlation coefficient showed moderate to strong correlation strength, even with up to 53 % cTnI concentrations variance (Passing Bablok slopes) vs 27.0-40.1 % (Bland-Altmann plots)., Conclusions: Up to 95 % of measured samples were > LoD for both the POC (Atellica VTLi) and central laboratory (Atellica IM) hs-cTnI assays. Moderate to strong concordance and correlation were observed between assays, despite up to 53 % variances in cTnI concentration., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Background: We evaluated the diagnostic performance of a whole blood, point of care (POC) high-sensitivity cardiac troponin I (hs-cTnI) assay for myocardial infarction (MI) compared to central laboratory assays., Methods: Consecutive patients presenting to the emergency department with symptoms of ischemia were studied. Serial hs-cTnI testing was based on clinical indication at presentation. Parallel measurements were made using fresh whole blood on Siemens Atellica VTLi POC assay, EDTA plasma on Abbott ARCHITECT i2000 used in practice, and heparin plasma on Siemens Atellica. MI was determined according to the Fourth Universal Definition of MI using 99th percentiles. Sensitivities and negative predictive values (NPV) were calculated using 99th percentile URLs., Results: 1089 Patients, 418 females and 671 males, were enrolled. There were 91 (8.4%) MIs. At baseline (0 h), POC hs-cTnI assay had a sensitivity of 65.7% (95% CI 47.8-80.9) for females and 67.9% (54.0-79.7) for males and NPV of 96.4% (93.9-98.1) for females and 96.7% (94.9-98.0) for males. At 2 h, sensitivity improved to 82.9% (66.4-93.4) for females and 80.4% (67.6-89.8) for males, while NPV improved to 98.2% (96.1-99.3) and 97.9% (96.3-99.0), respectively. For central laboratory assays, comparable diagnostics were observed at 2 h: females - sensitivity 94.3% (80.8-99.3) for ARCHITECT and 79.4% (62.1-91.3) for Atellica, and NPV 99.3% (97.6-99.9) and 98.0% (95.8-99.2), respectively; males - sensitivity 87.5% (75.9-94.8) for ARCHITECT and 80.4% (67.6-89.8) for Atellica, NPVs of 98.7% (97.3-99.5) and 97.9% (96.3-99.0), respectively., Conclusions: The POC, whole blood Atellica VTLi hs-cTnI assay demonstrated comparable diagnostic accuracy for MI to central laboratory assays using 99th percentiles., (Copyright © 2022 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Background: This study aimed to compare the incidence of cardiac troponin I (cTnI) concentrations above the limit of quantification (LOQ) and the sex-specific 99th percentile upper reference limits (URLs) between the Ultra contemporary cTnI assay and the high-sensitivity (hs-cTnI) assay on Siemens Centaur in patients evaluated in the emergency department (ED) and inpatient at a U.S. urban academic hospital., Methods: A retrospective study was performed in an unselected patient cohort who presented to the hospital with symptoms suggestive of myocardial injury. All clinically ordered samples for cTnI assay (n = 1,056, LOQ 0.03 µg/L, URL 0.04 µg/L) were simultaneously tested on the hs-cTnI assay (LOQ 2.5 ng/L; URL 58 ng/L and 39 ng/L for male and female, respectively)., Results: The incidence of elevated cTnI above the 99th percentile URL in males measured by the hs-cTnI assay was significantly lower compared to the cTnI assay (31.4% vs. 38.7%, p = 0.016), whereas there was no difference in females (27.4% vs. 30.2%, p = 0.35) in all the patient samples. In ED patient samples (n = 718), the incidence of elevated cTnI above the sex-specific 99th percentile URL was not significantly different between the hs-cTnI and contemporary cTnI assays in either sex (male: hs-cTnI 16.6% vs. cTnI 21.5%, p = 0.13; female: hs-cTnI 19.6% vs. cTnI 21.1%, p = 0.66). The agreement between the two assays was 93.5% (kappa = 0.798). Results were confirmed in an independent patient cohort measured by the same instruments at another hospital., Conclusion: Our study suggests that implementation of the hs-cTnI assay would not lead to an increase in the proportion of elevated cTnI above the 99th percentile in the emergency department and other inpatient units., (Copyright © 2020 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Objective: A multisite investigation compared the analytical performance of a point-of-care (POC) HbA1c device with multiple commonly used HbA1c laboratory methods and an NGSP (National Glycohemoglobin Standardization Program) reference method., Research Design and Methods: The Afinion AS100 POC device analyzed HbA1c using 618 EDTA whole blood excess patient specimens with clinically indicated HbA1c testing. Results were compared to measurements across five clinical laboratories and the NGSP reference method. Precision was evaluated over 8-10 consecutive days for low-, mid-, and high-range HbA1c specimens at all five sites., Results: Over a wide range of HbA1c values (4.0%-15% HbA1c), 97.1% of the POC results and 94.5% of routine laboratory results fell within the target value of ±6% of the NGSP reference method results. The POC HbA1c results at 6.5% exhibited a total relative bias of -0.6% (-0.04% HbA1c) compared to the reference method while the aggregate of laboratory methods displayed a relative bias of -0.9% (-0.06% HbA1c). The total imprecision of the POC results ranged from 0.74-2.13% CV across the analytic measurement range compared to 0.81-3.23% CV for the routine laboratory methods., Conclusions: The accuracy and precision of the Afinion POC HbA1c method was comparable to the laboratory HbA1c methods supporting the FDA's recent approval of the Afinion HbA1c Dx device for use in the diagnosis of diabetes., (Published by Elsevier Inc.)

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/1.73m 2 ) 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., (Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Objectives: The HEART Pathway combines a decision aid and serial contemporary cardiac troponin I (cTnI) measures to achieve >99% sensitivity for major adverse cardiac events (MACE) at 30days and early discharge rates >20%. However, the impact of integrating high-sensitivity troponin (hs-cTn) measures into the HEART Pathway has yet to be determined. In this analysis we compare test characteristics of the HEART Pathway using hs-cTnI, hs-cTnT, or cTnI., Design & Methods: A secondary analysis of participants enrolled in the HEART Pathway RCT was conducted. Each patient was risk stratified by the cTn-HEART Pathway (Siemens TnI-Ultra at 0- and 3-h) and a hs-cTn-HEART Pathway using hs-cTnI (Abbott) or hs-cTnT (Roche) at 3-h. The early discharge rate, sensitivity, specificity, and negative predictive value (NPV) for MACE (death, myocardial infarction, or coronary revascularization) at 30days were calculated., Results: hs-cTnI measures were available on 133 patients. MACE occurred in 11/133 (8%) of these patients. Test characteristics for the HEART Pathway using serial cTnI vs 3hour hs-cTnI were the same: sensitivity (100%, 95%CI: 72-100%), specificity (49%, 95%CI: 40-58%), NPV (100%, 95%CI: 94-100%), and early discharge rate (45%, 95%CI: 37-54%). The HEART Pathway using hs-cTnT missed one MACE event (myocardial infarction): sensitivity (91%, 95%CI: 59-100%), specificity (48%, 95%CI: 39-57%), NPV (98%, 95%CI: 91-100%), and early discharge rate (45%, 95%CI: 37-54%)., Conclusions: There was no difference in the test characteristics of the HEART Pathway whether using cTnI or hs-cTnI, with both achieving 100% sensitivity and NPV. Use of hs-cTnT with the HEART Pathway was associated with one missed MACE., (Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Cardiac troponin (cTn) is the biomarker of choice for assessment of patients with acute coronary syndromes. Guidelines recommend the cTn 99th percentile derived from a cardiovascular healthy reference population as decision threshold. The importance of standardized criteria for the composition of such a reference population is well acknowledged. In this analysis, we investigated to which extent different statistical methods might have bearing on the calculated cTnI 99th percentile., Methods: cTnI (Abbott) 99th percentiles were determined in 521 cardiovascular healthy community-dwelling subjects using the nonparametric method, the Harrell-Davis bootstrap method and the robust method together with different tests to identify potential outliers (Dixon, Tukey, Reed) and different statistical softwares., Results: The cTnI 99th percentiles (nonparametric method) were 37ng/L (total population), 42ng/L (men) and 25ng/L (women). These estimates differed by -7.4% to +5.7% using the Harrell-Davis bootstrap method and were up to 64.1% lower using the robust method. For the robust method, cTnI 99th percentiles varied by 44.2% depending on the applied software. The method of Tukey classified nine subjects as outliers while no outlier was detected using the other methods. Excluding these nine subjects resulted in up to 60.2% lower cTnI 99th percentiles., Conclusions: Our results emphasize the need of a standardized statistical approach to calculate cTnI 99th percentiles. Our findings support the use of the nonparametric method and a conservative approach to detect outliers. This requires that the assessed population is sufficiently large and well selected on the basis of stringently applied clinical criteria., (Copyright © 2016 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

In 2011, the IFCC Task Force on Clinical Applications of Cardiac Bio-Markers (TF-CB) was formed, with the purpose of providing evidence based educational materials to assist all biomarker users, i.e. laboratorians, clinicians, researchers, in-vitro diagnostics and regulatory agencies, in better understanding important analytical and clinical aspects of established and novel cardiac biomarkers for use in clinical practice and research. The goal of the task force was to promulgate the same information conjointly through the in vitro diagnostic industry to the laboratory, emergency department and cardiologists. The initial undertaking of the TF-CB, which is comprised of laboratory medicine scientists, emergency medicine physicians and cardiologists, was to address two key issues pertaining to implementing high-sensitivity cardiac troponin (hs-cTn) assays in clinical practice: the 99th percentile upper reference limit (URL) and calculating serial change values in accord with the Universal Definition of AMI. The highlights of both concepts from IFCC statements are described., (Copyright © 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Objectives: This article is a systematic review of the effectiveness of four practices (assay selection, decision point cardiac troponin (cTn) threshold selection, serial testing, and point of care testing) for improving the diagnostic accuracy Non-ST-Segment Elevation Myocardial Infarction (NSTEMI) in the Emergency Department., Design and Methods: The CDC-funded Laboratory Medicine Best Practices (LMBP) Initiative systematic review method for quality improvement practices was used., Results: The current ACC/AHA guidelines recommend using cardiac troponin assays with a 99th percentile upper reference limit (URL) diagnostic threshold to diagnose NSTEMI. The evidence in this systematic review indicates that contemporary sensitive cTn assays meet the assay profile requirements (sensitivity, specificity, PPV, and NPV) to more accurately diagnose NSTEMI than alternate tests. Additional biomarkers did not increase diagnostic effectiveness of cTn assays. Sensitivity, specificity, and NPV were consistently high and low PPV improved with serial sampling. Evidence for use of point of care cTn testing was insufficient to make recommendation, though some evidence suggests that use may result in reduction to patient length of stay and costs., Conclusions: Based on the review of and the LMBP(TM) A-6 Method criteria, we recommend the use of cardiac troponin assays without additional biomarkers using the 99th percentile URL as the clinical diagnostic threshold for the diagnosis of NSTEMI. We recommend serial sampling with one sample at presentation and at least one additional second sample taken at least 6h later to identify a rise or fall in the troponin level. No recommendation is made either for or against the use of point of care tests., Disclaimer: The findings and conclusions in this article are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention/the Agency for Toxic Substances and Disease Registry (CDC/ATSDR)., (Copyright © 2015. Published by Elsevier Inc.)

Objective: Using objective laboratory and clinical criteria to more accurately determine the 99th percentile values for cardiac troponin I and T., Design and Methods: We measured cardiac troponin T and cardiac troponin I with high-sensitivity assays in a large cohort of apparently healthy community subjects and calculated 99th percentiles for different sexes and ages. Subjects with possible subclinical disease were eliminated based on objective laboratory criteria, eGFR and NT-proBNP, and clinical criteria, history and examination and echocardiogram., Results: For men and women of all ages, separately, more than 50% of subjects were excluded using these criteria, with a lesser proportion of younger subjects being excluded. In men aged <75 years, the 99th percentile for cTnI decreased by more than 50% from 22.9 ng/L to 10.3 ng/L. In other age groups and for cTnT the decrease was smaller (%) but still considerable., Conclusions: For establishing cardiac troponin 99th percentiles, simply using self-reporting of health is insufficient. Objective laboratory measures and clinical and echocardiographic assessments are essential to define a healthy population, especially in older persons., (© 2013. Published by Elsevier Inc. on behalf of The Canadian Society of Clinical Chemists. All rights reserved.)

Objective: This study evaluated the diagnostic performance of four point-of-care (POC) cardiac troponin I (cTnI) assays compared to a central laboratory cTnI assay for detecting myocardial injury and diagnosing acute myocardial infarction (AMI)., Design and Methods: Plasma obtained at admission, 3 h, and 6 h post-admission in 169 patients presenting with symptoms suggestive of acute coronary syndrome (ACS) was studied. cTnI concentrations were measured on the Instrumentation Laboratory prototype GEM Immuno, Radiometer AQT90, Mitsubishi PATHFAST, Abbott i-STAT and the Ortho-Clinical Diagnostic Vitros assays. MI was determined based on 99th percentiles according to Universal MI guidelines., Results: For ruling in MI at presentation (0 h), the GEM Immuno (sensitivity 63%, specificity 85%) and PATHFAST (sensitivity 53%, specificity 86%) were comparable to the OCD (sensitivity 68%, specificity 81%), and significantly better (p<0.05) than the AQT90 (sensitivity 26%, specificity 93%) and i-STAT (sensitivity 32%, specificity 92%). cTnI concentrations and serial rising patterns after MI differed by each assay. Negative predictive values were >90% and ROC AUCs were >0.90 after 6h for all assays. Detection of myocardial injury in non-ischemic pathologies accounted for lower than 100% specificity for MI., Conclusion: cTnI is a sensitive biomarker for detection of myocardial injury. The analytical variability that exists between POC cTnI assays demonstrates substantial diagnostic differences for ruling in and ruling out MI in patients presenting with symptoms suggestive of ACS., (© 2013.)

Objectives: To design a predictive model for assessing the risk of developing respiratory distress syndrome (RDS) using gestational age (GA) and lamellar body counts (LBC)., Design and Methods: LBCs and patient outcome data was obtained from five medical centers. A total of 223 patients were included in this study; 19 gave birth to infants that developed RDS, 204 gave birth to infants that were unaffected. The absolute risk and odds ratios of an infant developing RDS as a function of GA and LBC were calculated. Logistic analysis was used to model the odds of RDS as a function of GA and LBC., Results: The odds of RDS decreased for each increasing week of GA and decreased with increase in the LBC. GA-specific LBC cutoffs are provided for sensitivities between 84 and 100%. The bias adjusted area under the ROC curve for the classification of RDS, based on GA and LBC, was 0.906 using the logistic model and 0.746 using a single cutoff of LBC (50,000/μL) to classify immaturity., Conclusions: GA-specific risk assessment and GA-specific cutoffs provide increased sensitivity and specificity in the evaluation of fetal lung maturity., (Copyright © 2013 The Canadian Society of Clinical Chemists. All rights reserved.)

Objective: The current study was undertaken to determine the relationship between postmortem (PM) peripheral blood (PB) and liver fentanyl concentrations and the role of measuring liver fentanyl concentrations in cause of death investigations in medical examiner cases in which fentanyl was identified., Design and Methods: FB and liver tissue were routinely collected at autopsy from 4 Minnesota medical examiners' offices in 2010-2011. Samples were analyzed by gas chromatography-mass spectrometry (GC-MS)., Results: PB fentanyl ranged from <2-15μg/L in non-drug related deaths (n=5), <2-22μg/L from mixed drug toxicity (n=26) and 3.7-56μg/L from fentanyl toxicity (n=33). Liver fentanyl ranged from 11 to 104μg/kg, 6 to 235μg/kg, and 18 to 365μg/kg, respectively. PB and liver fentanyl showed a modest correlation (r=0.67). PM interval to the liver/blood ratio showed a decreasing ratio over increasing PM interval in cases from fentanyl and mixed drug toxicity. Liver fentanyl concentrations best define therapeutic use at <23μg/kg and fatal toxicity at >56μg/kg, without substantial overlap as found in blood fentanyl concentrations., Conclusion: Discriminatory liver fentanyl concentrations suggestive of therapeutic or toxic drug levels may better assist cause of death determination in cases of suspected fentanyl toxicity than postmortem PB concentrations. Peripheral blood fentanyl concentrations appear to undergo postmortem redistribution, associated with an increasing PM interval., (Copyright © 2013 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

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)., (Copyright © 2012 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Objectives: We determined diagnostic accuracy and risk stratification using delta changes for the cardiac troponin I (cTnI) Centaur Ultra assay for ruling out acute myocardial infarction (AMI) and for risk prediction of adverse events in patients with symptoms of acute coronary syndrome., Design and Methods: cTnI was measured on admission and 6-24 h in 371 patients. Optimal deltas (percent change, absolute value of percent change, change, absolute value of change) were determined from ROC curve analysis. Risk stratification was performed for cardiac events and death within 60 days., Results: AMI during hospitalization occurred in 49 patients and endpoints in 11 patients. Diagnostic accuracy by ROC curve was optimal (0.96) using the absolute value of change delta. Diagnostic specificities utilizing the 99th percentile (40 ng/L) for admission and follow-up samples were 84% and 81%, compared to: [90% percent change delta] 89.7%; [66.7% absolute value of percent change delta] 85.5%, [217 ng/L change delta] 99.0% and [55 ng/L absolute value of change delta] 93.7%. All four delta values showed substantially greater risk when the initial cTn value was normal., Conclusions: Utilizing delta cTnI values improves clinical specificity, diagnostic accuracy and risk assessment in patients presenting with symptoms of ACS., (Copyright © 2012 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Objectives: Pregnancy Associated Plasma Protein A (PAPP-A)-derived N- and C-terminal fragments of IGF-binding protein-4 (NT- and CT-IGFBP-4) released from vulnerable atherosclerotic plaques are proposed to be used for cardiovascular risk assessment., Design and Methods: NT- and CT-IGFBP-4 were measured by novel immunoassays in EDTA-plasma of 180 patients admitted to the emergency department with symptoms of myocardial ischemia but without ST-segment elevation. Six-month incidence of major adverse cardiac events (MACE), including myocardial infarction, cardiac death, percutaneous coronary interventions, and coronary artery bypass grafting was recorded., Results: Sixteen patients met the endpoint. NT- and CT-IGFBP-4 were strong predictors of MACE: area under ROC curve (AUC) 0.856 and 0.809, respectively. NT-IGFBP-4 concentrations≥214μg/L and CT-IGFBP-4 concentrations≥124μg/L were associated with increased risk of future MACE: adjusted hazard ratio 13.79 and 7.93, respectively., Conclusions: IGFBP-4 fragments can be utilized as biomarkers for MACE prediction in patients with suspected myocardial ischemia., (Copyright © 2012 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Objectives: To compare plasma BNP values determined by a conventional-type and a novel-type of BNP assays., Design and Methods: Plasma samples (n=94) from HF patients were analyzed by the novel-type "Single Epitope Sandwich" (SES assay prototype) and the conventional-type Siemens ADVIA Centaur BNP assays. Both assays were calibrated using recombinant proBNP (expressed in E. coli)., Results: The SES assay measured 1.2- to 7.2-fold (2.1±0.9; mean, SD) greater BNP concentrations compared to the Siemens assay. A subset of six samples (6.4%) demonstrated the largest (3- to 7.2-fold higher) difference., Conclusions: The SES prototype assay appears to more accurately measure the absolute concentrations of BNP immunoreactive forms., (Copyright © 2010 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Objectives: This study determined the serum 99th percentile reference value for cTnI measured using the high sensitivity Erenna cTnI assay., Design and Methods: Serum was obtained from healthy adults (n=348); aged 18-76 years of which 147 were males and 201 were females. Nonparametric analysis was performed to determine the 99th percentiles., Results: For all subjects, the 99th percentile was 10.19 ng/L; mean concentration=1.45 ng/L, range=0.2 to 34.56 ng/L. By gender, the male and female 99th percentile values were as follows: male=16.58 ng/L, mean concentration=1.72 ng/L, and female=9.36 ng/L, mean concentration=1.25 ng/L, respectively (p=0.108)., Conclusion: cTnI measured by the high-sensitivity Erenna cTnI assay measured 100% of normal subjects, allowing prospective diagnostic and risk assessment studies to be performed, which are essential for the early detection of cardiac disease and for the management of patients presenting with symptoms suggestive of acute coronary syndrome., (2010 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)