BackgroundSwitching from a conventional to a high-sensitivity cardiac troponin (hs-cTn) assay enables detection of smaller amounts of myocardial damage, but the clinical benefit is unclear. We investigated whether switching to a hs-cTnI assay with a sex-specific 99th centile diagnostic threshold was associated with lower 1-year death or new myocardial infarction (MI) in patients with suspected acute coronary syndrome (ACS).MethodsThis pre–post study included nine tertiary hospitals in Australia. During the pre-hs-cTn period, all hospitals used conventional troponin assays, and during the postperiod, four switched to using hs-cTnI. Participants were ≥20 years old and presenting to emergency departments (EDs) with suspected ACS between March 2011 and November 2015. Outcomes were determined using linked administrative data and compared using Kaplan-Meier and Cox regression analyses.ResultsWe identified 179 681 consecutive patients (62 (SD 19) years, 47% women), 87 019 (48%) during the preperiod, and 92 662 (52%) during the postperiod. Following the switch to hs-TnI, the proportion of patients diagnosed with new MI was not significantly different (3.9% postperiod vs 4.2% preperiod; p=0.08) while diagnoses of unstable angina were lower (1.5% postperiod vs 2.5% preperiod; p<0.0001). In non-switching jurisdictions, rates of new MI remained stable, while diagnoses of unstable angina increased. Switching to hs-cTnI assay was associated with lower mortality at 30 days (adjusted HR 0.88 (0.82, 0.95)) and 1 year (aHR 0.90 (0.85, 0.94)). The corresponding aHRs for non-switching jurisdictions were not statistically different.ConclusionThe use of an hs-cTnI assay in an ED population with suspected ACS was associated with lower mortality at 1 year.

OBJECTIVES:Aldosterone is over-estimated by direct immunoassay when compared to assay by LC-MS/MS. We have investigated the mechanism for this over-estimation, using dichloromethane (DCM) extraction and a unique matrix of non-synthetic aldosterone-free plasma (ALFP). METHODS:Samples used were from patients with normal estimated Glomerular Filtration Rate (eGFR). All samples were measured by direct DiaSorin immunoassay, followed by extraction using dichloromethane (DCM) and LC-MS/MS. Post-DCM samples were reconstituted in DiaSorin Liaison Endocrinology Diluent (DED), which is effectively a human serum albumin matrix, or in a unique matrix of non-synthetic human aldosterone-free plasma (ALFP). Patient plasma samples were selected to cover a wide range of aldosterone concentrations. RESULTS:Aldosterone direct immunoassay over-estimated aldosterone concentration in all samples, compared to LC-MS/MS. Post-DCM extraction and reconstitution with DED, aldosterone results matched well with LC-MS/MS results. Reconstitution with our unique ALFP plasma matrix rather than the DED, resulted in an over-estimation of aldosterone by approximately 50 pmol/L in all samples. CONCLUSIONS:In this investigation, we have demonstrated that the most likely source of interference in the direct DiaSorin aldosterone immunoassay is an endogenous protein commonly found in patient samples. This protein probably interferes with the immunoassay by binding to the tracer.

The 99th percentile of cardiac troponin assays for determining the presence of acute myocardial infarction (AMI) was set when assay analytical performance was much less precise than currently and was chosen, in part, to reduce the frequency of 'false-positive' results. A result greater than 99th percentile criterion has been a requirement of each version of the universal definition of MI. It also became used as a dichotomous decision-making threshold in diagnostic strategies for investigating AMI in acute care settings. There are numerous difficulties in deriving the 99th percentile which undermine its reliability as a standalone test threshold. It is important for patient safety that all users are aware of the challenges and pitfalls of using the 99th percentile for decision-making. We present a focused review of the 99th percentile, highlighting some difficulties with its use as a decision threshold as well as possible adjunctive strategies and alternative approaches.

Background Switching from conventional to high-sensitivity cardiac troponin (hs-cTn) assays with sex-specific reference rates for threshold troponin levels enables detection of smaller amounts of myocardial damage. However, the real-world impact of these assays on patient outcomes and health service costs is poorly understood. We investigated the cost-effectiveness of switching to hs-cTn assays for patients presenting to Australian Emergency Departments (EDs) with suspected acute coronary syndrome (ACS) with a 12-month follow-up period. Methods Using linked administrative data from 9 tertiary hospitals for patients aged 20 and above who presented to ED with suspected ACS between March 2011 and November 2015, we applied a difference-in-differences methodology to compare costs and major adverse cardiac events between hospitals switching to hs-cTn assays and hospitals continuing to use conventional assays. Results We identified 179,681 consecutive patients, of whom 87,019 presented during the preperiod and 92,662 the postperiod. Switching to hs-cTn was associated with a reduction in the cost of the index event (-$1,022, 95% CI: -$1,034, -$1,009), a reduction in total costs at 12 months (-$1,373, 95% CI: -$1,387, -$1,360) and a reduction in the percentage of patients experiencing a MACE outcome within 12-months (-0.55%, 95% CI: -0.88%, -0.21%). The reduction in MACE outcomes was larger for female patients (-1.17%, 95% CI: -1.19%, -1.14%) than for all patients and for males. Conclusions The switch to hs-cTn is highly cost-effective across all patients and for each sex. The reduction in MACE outcomes and costs within 12 months are greater for females than for males.

Introduction: Several cases of newly positive thyroid autoantibodies (TA) following intravenous immunoglobulin (IVIG) administration were noted at ACT Pathology, prompting investigation into the presence of TA in IVIG solutions. Methods: 32 samples were collected from IVIG bottles. Samples were tested for thyroglobulin antibodies (anti-Tg) and thyroid peroxidase antibodies (anti-TPO) on the Abbott Alinity platform using chemiluminescent microparticle immunoassays (CMIAs). Serial dilutions were performed with the aim of simulating the expected dilution of IVIG that occurs in vivo on administration to patients (approximately 1:10 to 1:2 dilution for doses of 0.4 g/kg to 2 g/kg of IVIG, respectively). Results: All IVIG samples tested positive for the presence of TA with a mean (standard deviation) anti-Tg of 230 (88) kU/L and anti-TPO of 315 (89) kU/L. Dilutions with TA-negative serum demonstrated TA from IVIG remained detectable in the range of 1:2 to 1:32 dilutions tested. The TA levels in the 1:10 and 1:2 dilution were anti-Tg of 27 and 103 kU/L and anti-TPO of 35 and 139 kU/L, respectively. Conclusions: Our data supports the presence of TA in IVIG, and their passive acquisition through IVIG administration. Further investigation is required to assess the clinical significance of this.

Leakage of cerebrospinal fluid (CSF) can occur as a result of trauma, surgery, or it can be spontaneous. Confirmation that a sample of fluid suspected of being CSF is indeed CSF is important, as conservative management is associated with a high incidence of meningitis.1Bernal-Sprekelsen M. Alobin I. Mullol J. Trobar F. Tomas-Barberan M. Closure of cerebrospinal fluid leaks prevents ascending bacterial meningitis.Rhinology. 2005; 43: 277-281PubMed Google Scholar A recent review on the diagnosis of CSF rhinorrhoea identified glucose testing, beta-2 transferrin (B2T), beta trace protein (BTP) and radionuclide cisternography as potential diagnostic tools.2Oakley G.M. Alt J.A. Schlosser R.J. Harvey R.J. Orlandi R.R. Diagnosis of cerebrospinal fluid rhinorrhea: an evidence-based review with recommendations.Int Forum Allergy Rhinol. 2016; 6: 8-16Crossref PubMed Scopus (89) Google Scholar There is a considerable literature on use of B2T and BTP for identification of CSF leaks based on the higher concentration of these proteins in CSF compared to other fluids and blood.3Mantur M. Lukaszewicz-Zajac M. Mrokzko B. et al.Cerebrospinal fluid leakage – reliable diagnostic methods.Clin Chim Acta. 2011; 412: 837-840Crossref PubMed Scopus (49) Google Scholar However, performing these assays is time-consuming and results are not available in a timeframe to aid clinical decision making. The concentration of chloride is higher in CSF than it is in plasma: 118–132 mmol/L versus 98–107 mmol/L.4Tietz N.W. Clinical Guide to Laboratory Tests. WB Saunders Company, 1990Google Scholar We have used concurrent measurement of chloride in fluid queried to be CSF and plasma and compared it to B2T measurement on the same fluid sample. The ACT Health Human Research Ethics Committee advised us that this study fulfilled the criteria for a quality assurance study and formal ethics approval was not required. Because we get only occasional requests for B2T in fluid to aid in the diagnosis of CSF leaks, we send them to another laboratory with a turnaround time of several days. When we received a request for B2T we separated a small sample for chloride measurement and checked for plasma chloride measurements on the same subject. Where a measurement of plasma chloride had occurred within the last 12 hours, we used the paired fluid and plasma chloride measurements. A change in a result can be for any of a combination of three reasons: assay variation, biological variation (BV) and a pathological change. If the variation due to BV and assay impression can be calculated, then any further change indicates a pathological process is present. This boundary to separate assay and BV changes from pathological change is the reference change value (RCV) and for 95% confidence, this is 2.77 × combined SD. In our laboratory, at a chloride concentration of 98 mmol/L, the coefficient of variation (CV) is 0.78% or a standard deviation (SD) of 0.764 mmol/L. The BV of plasma chloride is very low with a CV of 1.2% (SD 1.17 mmol/L).5Fraser C.G. Biological Variation: From Principles to Practice. AACC Press, Washington DC2001Google Scholar For 95% confidence, the RCV is 3.9 mmol/L. In our analysis below we have compared (fluid chloride–plasma chloride) ≥+5 mmol/L and ≥+8 mmol/L as diagnostic criteria. Over a period of 6 years, we received only 55 requests for B2T on fluid samples queried to be CSF. Of the 55 samples, the clinical diagnosis was CSF leak in 44, no CSF leak in nine and uncertain in two. Thirty of these 55 samples were reported as positive for B2T consistent with the fluid being CSF; five were reported as negative or probably negative, and 20 were reported as contaminated, degraded, unsuitable or indeterminate. For the same 55 subjects, 13 did not have paired fluid–plasma chloride measurements (leaving 42 patients to review), 31 had a fluid–plasma chloride difference ≥+8 mmol/L and another four had a fluid-plasma chloride difference ≥+5 but <+8 mmol/L (35 fluid–plasma chloride difference ≥+5 mmol/L). Table 1A,B shows the relatedness between the clinical diagnosis and the chloride gradient (the difference between the fluid chloride and the plasma chloride). Only 42 patients also had plasma chloride measured. Of these 42 patients, 35 were adjudged clinically to have a CSF leak and of these 32 of 35 had a chloride difference of ≥+5 mmol/L, for a diagnostic sensitivity of 91.4%. If a chloride gradient of ≥+8 mmol/L was used the diagnostic sensitivity was 82.9%.Table 1Relationship between clinical diagnosis of CSF leak, B2T and chloride gradientAChloride ≥5 mmol/LClinicalPositiveNegativeNo samplePositive323944Negative3339Possible01123571355/55BChloride ≥8 mmol/LClinicalPositiveNegativeNo samplePositive296944Negative2439Possible011231111355/55CBeta-2 transferrin (B2T)ClinicalPositiveNegativeUnsuitablePositive3031144Negative0279Possible00223052055/55DChloride ≥5 mmol/LBeta-2 transferrinPositiveNegativeNo samplePositive260430Negative0055Unsuitable974203571355/55 Open table in a new tab A large proportion of the samples referred for B2T analysis had cautionary notes attached to the results indicating that there was evidence of either contamination by admixture of serous fluid or evidence of microbial presence. A total of 20 samples were identified in this manner (14 serous, 6 microbial, total 36.4%) and were excluded from further analysis of data. Table 1C shows the relatedness between the clinical diagnosis and the 35 samples available for B2T. Thirty of 33 suitable samples were positive for B2T for a diagnostic sensitivity of 90.9%. Table 1D shows the relatedness between B2T and a chloride gradient of ≥5 mmol/L, for the 26 samples which had both valid B2T results and chloride gradient results. There was 100% concordance between these two diagnostic modalities. Conservative management of a CSF leak is undesirable as significant complications may arise of which meningitis is the most feared. An array of radiological and chemical testing has been proposed to help in the clarification of this important medical problem.2Oakley G.M. Alt J.A. Schlosser R.J. Harvey R.J. Orlandi R.R. Diagnosis of cerebrospinal fluid rhinorrhea: an evidence-based review with recommendations.Int Forum Allergy Rhinol. 2016; 6: 8-16Crossref PubMed Scopus (89) Google Scholar There is a substantial literature on identification of a variety of proteins, e.g., B2T and BTP3Mantur M. Lukaszewicz-Zajac M. Mrokzko B. et al.Cerebrospinal fluid leakage – reliable diagnostic methods.Clin Chim Acta. 2011; 412: 837-840Crossref PubMed Scopus (49) Google Scholar and Dickkopf-related protein 3.6Michaelides E.M. Kuang H. Pieribone V.A. Dickkopf-related protein 3 as a sensitive and specific marker for cerebrospinal fluid leaks.Otol Neurotol. 2016; 37: 299-303Crossref Scopus (2) Google Scholar However, these tests all require specialised testing and results are not available in a clinically useful timeframe. Further, these tests are also subject to false results due to contamination or infection,7Korem M. Ovada H. Paldor I. et al.False negative β-2 transferrin in the diagnosis of cerebrospinal fluid leak in the presence of streptococcus pneumoniae.Laryngoscope. 2014; 125: 556-560Crossref Scopus (11) Google Scholar and admixtures of other fluids can make interpretation difficult. We were concerned that so many of the samples referred for B2T analysis were coming back with significant qualifications attached as to the validity of the results (20/55, 36.4%). In addition, the delay of several days in getting results back meant that while B2T was of potential value in hindsight, it offered nothing to the active clinical management of the patients with a suspected CSF leak. B2T has a high diagnostic sensitivity8Bachmann-Harilstad G. Diagnostic value of beta-2 transferrin and beta-trace protein as markers for cerebrospinal fistula.Rhinology. 2008; 46: 82-85Google Scholar and there is absolute concordance between B2T and the chloride gradient. This is potentially of great significance. If chloride has a diagnostic performance equivalent to B2T, and as chloride results can be turned around very quickly, this has the potential to be a game changer in assessing the patient with a possible CSF leak. Because very small numbers of subjects did not have a CSF leak, we are not able to provide meaningful data on the diagnostic specificity (the value of a negative result in the absence of disease) of the chloride gradient. This is of lesser importance. In cases where a potentially catastrophic outcome may result, diagnostic sensitivity (the true positive result rate) is of much greater importance. We believe our results are important for two particular reasons. One is that a simple test can provide useful data in a clinically useful timeframe, something which the currently accepted 'best test' cannot do. The second is that it highlights a 'real world' problem with use of B2T, the potential invalidity of results due to contamination. Considering the possible sites of CSF leaks and where they may drain, this is not surprising. It is a rare occurrence for laboratories to move from complex tests to simple tests. We believe we have provided evidence that concurrent measurement of fluid and plasma chloride has a useful place in the assessment of the patient with a possible CSF leak. The authors state that there are no conflicts of interest to disclose.

To improve birth outcomes, all pregnant women without known diabetes are recommended for an oral glucose tolerance test (OGTT) to screen for hyperglycaemia in pregnancy (diabetes in pregnancy or gestational diabetes mellitus (GDM)). This narrative review presents contemporary approaches to minimise preanalytical glycolysis in OGTT samples with a focus on GDM diagnosis using criteria derived from the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study. The challenges of implementing each approach across a diverse Australian healthcare setting were explored. Many Australian sites currently collect and transport OGTT samples at ambient temperature in sodium fluoride (NaF) tubes which is likely to lead to missed diagnosis of GDM in a significant proportion of cases. Alternative preanalytical solutions should be pragmatic and tailored to individual settings and as close as possible to the preanalytical conditions of the HAPO study for correct interpretation of OGTT results. Rapid centrifugation of barrier tubes to separate plasma could be suitable in urban settings provided time to centrifugation is strictly controlled. Tubes containing NaF and citrate could be useful for remote or resource poor settings with long delays to analysis but the impact on the interpretation of OGTT results should be carefully considered. Testing venous blood glucose at the point-of-care bypasses the need for glycolytic inhibition but requires careful selection of devices with robust analytical performance. Studies to evaluate the potential error of each solution compared to the HAPO protocol are required to assess the magnitude of misdiagnosis and inform clinicians regarding the potential impact on patient safety and healthcare costs.

Objectives Unlike many dose-response curves used in clinical chemistry, the immunoassay curve used to quantitate measurands is often sigmoidal rather than linear. Consequently, a more complex curve fitting model is required. Various models are available, but they can introduce bias, and there can be little awareness of why this error can be introduced. Content These curve-fitting models include those based on the law of mass-action, empirical models such as splines or linearization models such as the log/logit function. All these models involve assumptions, which can introduce bias as the dose-response curve is 'forced' to fit or minimize the distance between the standard concentration points to the theoretical curve. The most common curve fitting model is the four or five parameter model, which uses four or five parameters to fit a sigmoidal curve to a set of standard points. Summary and outlook Measurement of cardiac troponin is an important element in establishing a diagnosis of acute myocardial infarction. We use troponin, a cardiac biomarker, to demonstrate the potential effect of the bias that the curve fit could introduce. Troponin is used for both rule-in and rule-out decisions at different concentrations and at either end of the dose-response curve. The curve fitting process can cause lot-to-lot reagent (and calibrator) variation in immunoassay. However, laboratory staff need to be aware of this potential source of error and why it occurs. Understanding how the error occurs leads to a greater awareness of the importance of validating new reagent/calibrator assessment using patient samples with concentrations at crucial decision points.

Troponins are proteins that are integral components of the contractile mechanism of muscle, including cardiac muscle. Cardiac troponins Iand T can be detected in the blood of most people after puberty, at concentrations reflecting cardiac mass, sex and age. Current laboratory assays are approximately 1000 times more sensitive than those used previously. They also have higher sensitivity than point-of-care assays. The measurement of cardiac troponins is used primarily to assist in the diagnosis or exclusion of myocardial injury. Serial tests in acute coronary syndrome are guided by the Universal Definition of Myocardial Infarction.

Abstract Objectives Knowing the intra-individual variation (CVi), also termed within subject biological variation, of an analyte is essential to properly interpret apparent changes in concentration. While there have been many studies assessing the CVi of cardiac troponin (cTnI), they have been limited in looking at CVi in different settings, and there is no data available on whether CVi might change in different settings. Methods We used our large cTnI data bank to look at the CVi of cTnI in Emergency Department (ED) patients who had an acute myocardial infarction event excluded. We looked at the effects of gender, age, climatic season, and time between samples to assess whether CVi changed. To assess the effect of age, after exclusion, we collected two samples from each subject for each study which were used to calculate the CVi between those identified groups. There were 139 males and 98 females aged <65 years and 109 males and 98 females aged ≥65 years. For gender and season, there were 122 males and 94 females in the summer period and 126 males and 102 females in the winter period. To assess long term variation there were 195 males and 153 females who had further admissions after more than 12 months. Results For the four variables listed, there were no significant differences in within individual variation (CVi), but there was a significant difference in between individual variation (CVg) for men and women with regard to age. The Index of Individuality (II) was <0.20 for all conditions studied. We noted that >90% of subjects had an reference change value (RCV) <9 ng/L. Conclusions Because troponin concentration in patients without an identified cardiac condition change so little, delta changes are potentially of great value in assessing patients in the ED. Significant delta changes in troponin can occur without the 99th percentile being exceeded.

Troponins are proteins that are integral components of the contractile mechanism of muscle, including cardiac muscle. Cardiac troponins I and T can be detected in the blood of most people after puberty, at concentrations reflecting cardiac mass, sex and age. Current laboratory assays are approximately 1000 times more sensitive than those used previously. They also have higher sensitivity than point-of-care assays. The measurement of cardiac troponins is used primarily to assist in the diagnosis or exclusion of myocardial injury. Serial tests in acute coronary syndrome are guided by the Universal Definition of Myocardial Infarction.

BACKGROUND: Reference intervals are an important aid in medical practice as they provide clinicians a guide as to whether a patient is healthy or diseased. Outlier results in population studies are removed by any of a variety of statistical measures. We have compared several methods of outlier removal and applied them to a large body of analytes from a large population of healthy persons. METHODS: We used the outlier exclusion criteria of Reed-Dixon and Tukey and calculated reference intervals using nonparametric and Harrell-Davis statistical methods and applied them to a total of 36 different analytes. RESULTS: Nine of 36 analytes had a greater than 20% difference in the upper reference limit, and for some the difference was 100% or more. CONCLUSIONS: For some analytes, great importance is attached to the reference interval. We have shown that different statistical methods for outlier removal can cause large changes to reported reference intervals. So that population studies can be readily compared, common statistical methods should be used for outlier removal.

OBJECTIVE Preanalytical processing of blood samples can affect plasma glucose measurement because ongoing glycolysis by cells prior to centrifugation can lower its concentration. In June 2017, ACT Pathology changed the processing of oral glucose tolerance test (OGTT) blood samples for pregnant women from a delayed to an early centrifugation protocol. The effect of this change on the rate of gestational diabetes mellitus (GDM) diagnosis was determined. RESEARCH DESIGN AND METHODS All pregnant women in the Australian Capital Territory (ACT) are recommended for GDM testing with a 75-g OGTT using the World Health Organization diagnostic criteria. From January 2015 to May 2017, OGTT samples were collected into sodium fluoride (NaF) tubes and kept at room temperature until completion of the test (delayed centrifugation). From June 2017 to October 2018, OGTT samples in NaF tubes were centrifuged within 10 min (early centrifugation). RESULTS A total of 7,509 women were tested with the delayed centrifugation protocol and 4,808 with the early centrifugation protocol. The mean glucose concentrations for the fasting, 1-h, and 2-h OGTT samples were, respectively, 0.24 mmol/L (5.4%), 0.34 mmol/L (4.9%), and 0.16 mmol/L (2.3%) higher using the early centrifugation protocol (P< 0.0001 for all), increasing the GDM diagnosis rate from 11.6% (n= 869/7,509) to 20.6% (n= 1,007/4,887). CONCLUSIONS The findings of this study highlight the critical importance of the preanalytical processing protocol of OGTT blood samples used for diagnosing GDM. Delay in centrifuging of blood collected into NaF tubes will result in substantially lower rates of diagnosis than if blood is centrifuged early.

BackgroundGestational diabetes mellitus (GDM) is glucose intolerance first diagnosed during pregnancy not due to overt diabetes. Recent changes to the diagnostic guidelines have been shown to increase the apparent occurrence of GDM.AimThe aim of this study was to compare retrospectively the neonatal outcomes between groups defined using the new and old criteria to assess the impact of guideline changes on pregnancy outcomes.MethodsThe study was of singleton babies delivered of 641 women, who had oral glucose tolerance testing and pregnancy care at a single tertiary centre between 2011 and 2015.ResultsCompared to the population of women not now considered to have GDM by International Association of Diabetes and Pregnancy Study Groups criteria (two‐hour glucose concentration ≤8.4 mmol/L), neonates born to women with the new lower fasting criterion (5.1–5.4 mmol/L) and/or the new 60‐min group (glucose ≥10 mmol/L) combined were significantly more likely to have birthweight ≥90th percentile (22% vs 5%, P < 0.0001). In contradistinction, there was a significant excess number of small‐for‐dates babies (birthweight ≤10th percentile) in all subgroups previously diagnosed and treated for GDM by the Australian Diabetes in Pregnancy Society criteria (17% vs 7%, P = 0.001). Rates for lower uterine segment caesarean section, admission to the neonatal intensive care unit / special care nursery and Apgar scores at one and five minutes were not statistically different across all groups.ConclusionsOutcomes support the lowering of the fasting criterion to extend management of GDM to limit growth of large birthweight neonates. An unexpected outcome was that in women previously treated for GDM, there were increased numbers of low‐birthweight neonates.

BACKGROUND:Because the 99th percentile is of such importance in defining myocardial injury and myocardial infarction, it is important to know whether there are real age-related differences in troponin 99th percentiles. METHODS:We went to our database from the Canberra Heart Study where 1062 apparently healthy subjects were extensively screened for occult cardiac disease, and looking at persons aged <65 years and >65 years, for men and women separately, we compared a variety of cutpoints from the 99th percentile down to the 50th percentile. RESULTS:With our rigorous criteria for defining cardiac health, we excluded 67.2% of males aged >65 years and 53.8% of women aged 65 years and older. Even with these rigorous exclusions we found that at every cutpoint examined between the 99th percentile and the 50th percentile, persons aged <65 years had lower troponin I concentrations that persons aged 65 years and older. Similarly, at every cutpoint examined, women had lower troponin I concentrations than did men. For the 4 separate groups examined (men and women, age < 65 years and 65 years and older) after the exclusions of persons with subclinical cardiac disease, the distributions were not significantly different to a Gaussian distribution. CONCLUSIONS:With the rigorous exclusions of persons with subclinical cardiac disease, and the fact that our populations have a Gaussian distribution, our data suggests that age-related hs-cTnI concentrations are real. This has important implications particularly when assessing older persons in the Emergency Department.

Background: With the advent of the new high-sensitivity troponin assays, it is becoming critical to measure troponin accurately to low concentrations. To ensure assay performance is acceptable, appropriate QC must be run. Methods: In addition to the routine use of commercial QC material, we prepared pools of human QC material with low troponin concentrations close to the limit of quantitation, and ran these regularly on our laboratory analysers. Results: Over 3 years we found no drift or shift in our hs-cTnI assay. We found that only the very low concentration human QC material gave warning of precision problems with the hs-cTnI assay. M the time of the documented poor assay precision, the higher concentration QC material indicated satisfactory performance. Conclusions: Choice of QC material with an appropriate concentration is important for any assay. For hs-cTn assays, it is of particular importance to use control material with a concentration near to the limit of quantitation.

OBJECTIVES:While persons with overt renal failure have a well-described rise in troponin and NT-proBNP, it is less well described what the relationship is between cardiac markers and persons with impaired renal function, not requiring dialysis.DESIGN & METHODS:We have collected ALL samples referred to our pathology practice over a 24h period and measured hs-cTnI, hs-cTnT, NT-proBNP, calculated the eGFR, and related our measurements to clinical outcomes.RESULTS:For both men and women, for all of hs-cTnI, hs-cTnT and NT-proBNP, there was a graded response, as renal function worsened, the concentration of the cardiac marker increased.CONCLUSIONS:There is a graded inverse relationship between eGFR and the concentrations of hs-cTnI, hs-cTnT and NT-proBNP. For women only there appeared to be an increase in mortality at lowest eGFR.