Abstract
The International Federation of Clinical Chemistry Committee on Clinical Application of Cardiac Bio-Markers provides evidence-based educational documents to facilitate uniform interpretation ...and utilization of cardiac biomarkers in clinical laboratories and practice. The committee’s goals are to improve the understanding of certain key analytical and clinical aspects of cardiac biomarkers and how these may interplay in clinical practice. Measurement of high-sensitivity cardiac troponin (hs-cTn) assays is a cornerstone in the clinical evaluation of patients with symptoms and/or signs of acute cardiac ischemia. To define myocardial infarction, the Universal Definition of Myocardial Infarction requires patients who manifest with features suggestive of acute myocardial ischemia to have at least one cTn concentration above the sex-specific 99th percentile upper reference limit (URL) for hs-cTn assays and a dynamic pattern of cTn concentrations to fulfill the diagnostic criteria for MI. This special report provides an overview of how hs-cTn 99th percentile URLs should be established, including recommendations about prescreening and the number of individuals required in the reference cohort, how statistical analysis should be conducted, optimal preanalytical and analytical protocols, and analytical/biological interferences or confounds that can affect accurate determination of the 99th percentile URLs. This document also provides guidance and solutions to many of the issues posed.
Cardiac troponins constitute essential components of the cardiac contractile apparatus and are released into the bloodstream following cardiomyocyte injury. Because of their cardiac specificity, ...cardiac troponin I or T are the recommended biomarkers for diagnosing acute myocardial infarction. However, cardiac troponin concentrations also frequently increase acutely after strenuous prolonged exercise, making the interpretation of cardiac troponin test results in patients presenting with acute chest pain challenging. This acute troponin response following exercise is commonly considered to be physiological and without adverse long-term consequences, but the possibility of exercise-induced, minor myocardial injury that may become clinically relevant if repeated over decades, has not been ruled out. Attempts to biochemically differentiate between physiological cardiac troponin release versus release after acute ischemic myocardial injury has so far proved largely unsuccessful, but future measurement of specific troponin fragments could be promising. Cardiac troponins also provide strong prognostic information across the spectrum of cardiovascular (CV) disease (CVD). In the chronic setting, low-level elevation of cardiac troponins has been associated with adverse outcome, and concentrations even within the normal range provide independent information concerning risk of developing heart failure (HF) and CVD death. Exercise exerts many beneficial effects on the CV system, and longitudinal observational data from epidemiological studies suggest that higher physical activity (PA) is associated with lower concentrations of cardiac troponins. Conversely, a sedentary life-style has been associated with higher cardiac troponin concentrations and a parallel increase in the risk of HF. Serial measurement of cardiac troponins using high sensitivity assays for monitoring the effect of life-style intervention, including PA appears promising.
The International Federation of Clinical Chemistry and Laboarator Medicine (IFCC) Committee on Clinical Applications of Cardiac Bio-Markers (C-CB) has provided evidence-based educational resources to ...aid and improve the understanding of important analytical and clinical aspects of cardiac biomarkers. The present IFCC C-CB educational report focuses on recommendations for appropriate use, analytical performance, and gaps in clinical studies related to the use of cardiac troponin (cTn) by point of care (POC) measurement, often referred to as a point of care testing (POCT). The use of high-sensitivity (hs)-cTn POC devices in accelerated diagnostic protocols used in emergency departments or outpatient clinics investigating acute coronary syndrome has the potential for improved efficacy, reduction of length of stay and reduced costs in the health care system. POCT workflow integration includes location of the instrument, assignment of collection and testing responsibility to (non-lab) staff, instrument maintenance, in-service and recurrent training, quality control, proficiency assessments, discrepant result trapping, and troubleshooting and inventory management.
The ESC algorithm requires that a difference of <3 ng/L can be detected (4) and, by implication, that there is an absolute RCV (8) value of <3 ng/L. Because cardiac troponin is reported in whole ...numbers, the actual lowest detectable 8 value should be 2 ng/L. ...the hs-cTnT assay showed satisfactory analytical precision when using 2 Cobas e801 modules, but laboratories should still verify their CVA locally before implementing the ESC rule-out algorithm. Hormone Laboratory Haukeland University Hospital PO Box 1400 5021 Bergen, Norway E-mail kristin.moberg.aakre@helse-bergen.no Previously published online at DOI: 10.1373/clinchem.2018.298703 1 Nonstandard abbreviations: ESC, European Society of Cardiology; NSTEMI, non-ST elevation myocardial infarction; hs-cTnT, high-sensitivity cardiac troponin T; CVA, analytical variation; RCV, reference change values; CV,, intra-individual biological variation.
Urinary excretion of albumin indicates kidney damage and is recognized as a risk factor for progression of kidney disease and cardiovascular disease. The role of urinary albumin measurements has ...focused attention on the clinical need for accurate and clearly reported results. The National Kidney Disease Education Program and the IFCC convened a conference to assess the current state of preanalytical, analytical, and postanalytical issues affecting urine albumin measurements and to identify areas needing improvement.
The chemistry of albumin in urine is incompletely understood. Current guidelines recommend the use of the albumin/creatinine ratio (ACR) as a surrogate for the error-prone collection of timed urine samples. Although ACR results are affected by patient preparation and time of day of sample collection, neither is standardized. Considerable intermethod differences have been reported for both albumin and creatinine measurement, but trueness is unknown because there are no reference measurement procedures for albumin and no reference materials for either analyte in urine. The recommended reference intervals for the ACR do not take into account the large intergroup differences in creatinine excretion (e.g., related to differences in age, sex, and ethnicity) nor the continuous increase in risk related to albumin excretion.
Clinical needs have been identified for standardization of (a) urine collection methods, (b) urine albumin and creatinine measurements based on a complete reference system, (c) reporting of test results, and (d) reference intervals for the ACR.
The International Federation of Clinical Chemistry Committee on Clinical Applications of Cardiac Biomarkers (IFCC C-CB) provides educational documents to facilitate the interpretation and use of ...cardiac biomarkers in clinical laboratories and practice. Our aim is to improve the understanding of certain key analytical and clinical aspects of cardiac biomarkers and how these may interplay. Measurements of cardiac troponin (cTn) have a prominent place in the clinical work-up of patients with suspected acute coronary syndrome. It is therefore important that clinical laboratories know how to recognize and assess analytical issues. Two emerging analytical issues resulting in falsely high cTn concentrations, often several fold higher than the upper reference limit (URL), are antibody-mediated assay interference due to long-lived cTn-antibody complexes, called macrotroponin, and crosslinking antibodies that are frequently referred to as heterophilic antibodies. We provide an overview of antibody-mediated cTn assay interference and provide recommendations on how to confirm the interference and interpret the results.
Myocardial infarction (MI) is diagnosed by the finding of a single cardiac troponin value above the 99th percentile and a significant time-dependent change in cardiac troponin concentration. The aim ...of this study was to determine the 90-min and weekly biological variations, the reference change value (RCV), and the index of individuality (II) of high-sensitivity cardiac troponin T (hs-cTnT) (Roche Diagnostics) and hs-cTnI (Abbott Diagnostics) in patients receiving hemodialysis (HD) and in healthy individuals.
Blood samples were collected from 19 HD patients (on an HD-free day) and 20 healthy individuals at 90-min intervals over a 6-h period (between 08:30 and 14:30) and before the midweek HD treatment for 10 weeks. The within-person variation (CVi), between-person variation, RCV, and II were calculated.
During the 6-h sampling period, the concentrations of hs-cTnT (both groups) and hs-cTnI (HD patients only) decreased on average by 0.8% to 1.7% per hour, respectively. These declining trends were included in the calculation of a 90-min asymmetric RCV: -8%/+5% in HD patients (hs-cTnT), -18%/+21% in HD patients (hs-cTnI), -27%/+29% in healthy individuals (hs-cTnT), and -39%/+64% in healthy individuals (hs-cTnI). The II was low in both groups for both assays. The weekly CVi values were approximately 8% (hs-cTnT) and 15% (hs-cTnI) in both groups.
When using a cardiac troponin change of 20%-50% to diagnose an MI, the false-positive rate is likely to be lower for the hs-cTnT assay than for the hs-cTnI assay. The low II suggests that use of a diagnostic cutoff value can be omitted.
Abstract
Background
Acute chest pain is associated with an increased risk of death and cardiovascular events even when acute myocardial infarction (AMI) has been excluded. Growth differentiation ...factor-15 (GDF-15) is a strong prognostic marker in patients with acute chest pain and AMI, but the prognostic value in patients without AMI is uncertain. This study sought to investigate the ability of GDF-15 to predict long-term prognosis in patients presenting with acute chest pain without AMI.
Methods
In total, 1320 patients admitted with acute chest pain without AMI were followed for a median of 1523 days (range: 4 to 2208 days). The primary end point was all-cause mortality. Secondary end points included cardiovascular (CV) death, future AMI, heart failure hospitalization, and new-onset atrial fibrillation (AF).
Results
Higher concentrations of GDF-15 were associated with increased risk of death from all causes (median concentration in non-survivors vs survivors: 2124 pg/mL vs 852 pg/mL, P < 0.001), and all secondary end points. By multivariable Cox regression, GDF-15 concentration ≥4th quartile (compared to <4th quartile) remained an independent predictor of all-cause death (adjusted hazard ratio (HR): 2.75; 95% CI, 1.69–4.45, P < 0.001), CV death (adjusted HR: 3.74; 95% CI, 1.31–10.63, P = 0.013), and heart failure hospitalization (adjusted HR: 2.60; 95% CI, 1.11–6.06, P = 0.027). Adding GDF-15 to a model consisting of established risk factors and high-sensitivity cardiac troponin T (hs-cTnT) led to a significant increase in C-statistics for prediction of all-cause mortality.
Conclusions
Higher concentrations of GDF-15 were associated with increased risk of mortality from all causes and risk of future CV events.
We undertook this study to evaluate method differences for 5 components analyzed by immunoassays, to explore whether the use of method-dependent reference intervals may compensate for method ...differences, and to investigate commutability of external quality assessment (EQA) materials.
Twenty fresh native single serum samples, a fresh native serum pool, Nordic Federation of Clinical Chemistry Reference Serum X (serum X) (serum pool), and 2 EQA materials were sent to 38 laboratories for measurement of cobalamin, folate, ferritin, free T4, and thyroid-stimulating hormone (TSH) by 5 different measurement procedures Roche Cobas (n = 15), Roche Modular (n = 4), Abbott Architect (n = 8), Beckman Coulter Unicel (n = 2), and Siemens ADVIA Centaur (n = 9). The target value for each component was calculated based on the mean of method means or measured by a reference measurement procedure (free T4). Quality specifications were based on biological variation. Local reference intervals were reported from all laboratories.
Method differences that exceeded acceptable bias were found for all components except folate. Free T4 differences from the uncommonly used reference measurement procedure were large. Reference intervals differed between measurement procedures but also within 1 measurement procedure. The serum X material was commutable for all components and measurement procedures, whereas the EQA materials were noncommutable in 13 of 50 occasions (5 components, 5 methods, 2 EQA materials).
The bias between the measurement procedures was unacceptably large in 4/5 tested components. Traceability to reference materials as claimed by the manufacturers did not lead to acceptable harmonization. Adjustment of reference intervals in accordance with method differences and use of commutable EQA samples are not implemented commonly.
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