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Secretoneurin (SN) is a novel cardiac biomarker that associates with the risk of mortality and dysfunctional cardiomyocyte Ca2+ handling in heart failure patients. Reference intervals for SN are unknown.SN was measured with a CE-marked ELISA in healthy community dwellers from the fourth wave of the Trøndelag Health Study (HUNT4) conducted in 2017–2019. The common, sex and age specific 90th, 95th, 97.5th and 99th percentiles were calculated using the non-parametric method and outlier exclusion according to the Reed test. The applicability of sex and age specific reference intervals were investigated using Harris and Boyd test. We also estimated the percentiles in a subset with normal findings on echocardiographic screening.The total cohort included 887 persons (56.4 % women). After echocardiographic screening 122 persons were excluded, leaving a total of 765 persons (57.8 % women). The 97.5th percentile (95 % CI in brackets) of SN was 59.7 (57.5–62.1) pmol/L in the total population and 58.6 (57.1–62.1) pmol/L after echocardiography screening. In general, slightly higher percentiles were found in women and elderly participants, but less than 4 % in these subgroups had concentrations deviating from the common 97.5th percentile. Low BMI or eGFR was also associated with higher concentrations of SN.Upper reference limits for SN were similar amongst healthy adult community dwellers regardless of prescreening including cardiac echocardiography or not. Women and elderly showed higher concentrations of SN, but the differences were not sufficiently large to justify age and sex stratified upper reference limits. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Keywords: Editorials; adolescent; child; heart disease; reference values; troponin EN Editorials adolescent child heart disease reference values troponin 17 19 3 06/30/23 20230704 NES 230704 Cardiac troponin is released into the circulation after myocardial injury. Any clinical guidance available is derived from data from small studies.[4] With the exception of rare cases of Kawasaki disease due to vasculitis and coronary artery aneurysm formation, myocardial infarction does not occur in children. Sex-specific versus overall clinical decision limits for cardiac troponin I and T for the diagnosis of acute myocardial infarction: a systematic review. [Extracted from the article]

• Biological variation data is vital for analyzing and interpreting biomarker results. • Secretoneurin is a novel biomarker associated with arrhythmogenesis and mortality. • Secretoneurin shows low analytical and biological variation in healthy subjects. • Secretoneurin has low reference change values and index of individuality. • Secretoneurin delta values may reflect risk of cardiac arrhythmias and mortality. Secretoneurin is a novel prognostic biomarker that may predict mortality in heart failure and the occurrence of ventricular arrhythmias. This study reports the within subject variation (CV I), between subject variation (CV G), reference change values (RCV) and index of individuality (II) of secretoneurin. Thirty healthy volunteers were included. Non-fasting samples were obtained between 8 and 10 am once a week for ten weeks. Secretoneurin was analyzed in duplicate using ELISA. No outliers were present according to Burnett and Reeds' criteria. Simple linear regression did not identify significant trends. Variance homogeneity in the analytical variance and CV I were tested using Cochrane's and Bartlett's tests and four participants were excluded. Calculation of CV I , CV G and RCV were done on ln transformed data as described by Fokkema, the II was calculated using retransformed data. The median age of the participants was 36 years and 53% were female. Non-fasting glucose, eGFR (CKD-EPI) , cTnT and NT-proBNP concentrations were within the normal range. Median secretoneurin concentrations were 38 pmol/L (women) and 33 pmol/L (men), p-value < 0.001. CV I and CV G were 9.8% (CI 8.7% to 11.0%) and 20.0 (CI 15.4% to 28.0%), respectively. RCV were 38.7% (CI 35.5% to 42.7%) and −27.9 (CI −29.9 to −26.2) and the II were 0.60 (CI 0.42–0.78). No gender differences were present. Secretoneurin has a fairly low CV I , CV G , RCV and II, indicating that it could be suitable as a diagnostic or prognostic biomarker and that delta values in serial samplings may be preferable for identifying clinical changes. [ABSTRACT FROM AUTHOR]

Morbid obesity is a risk factor for cardiovascular disease. The relative effects of Roux-en-Y gastric bypass surgery (GBS) and intensive lifestyle intervention (ILI) on subclinical myocardial injury, the activity of the cardiac natriuretic system, and systemic inflammation remain unclear. In a 59-week non-randomized clinical trial that included 131 patients with morbid obesity, we compared the effects of GBS and ILI on concentrations of cardiac troponin T (cTnT) and I (cTnI), N-terminal pro-B-type natriuretic peptide (NT-proBNP) and C-reactive protein (CRP). In the GBS and ILI group, median body mass index (BMI) was reduced by 14.4 kg/m2 versus 3.9 kg/m2, respectively (p value < 0.001). Cardiac troponins decreased after GBS, p = 0.014 (cTnT) and p = 0.065 (cTnI) and increased significantly in those treated with ILI (p values ≤ 0.021) (between-group differences for deltas: p ≤ 0.003). NT-proBNP increased in both groups, but significantly more in the GBS than in the ILI group (between-group differences for deltas: p = 0.008). CRP decreased significantly within the GBS and the ILI group, with this change significantly greater in the GBS group (between-group differences for deltas p < 0.001). The dominating mediator of the biomarker changes was weight loss. Prior coronary artery disease and diabetes were predictive of the magnitude of the changes in cTnI and NT-proBNP, respectively. Compared to ILI, GBS was associated with reduced subclinical myocardial injury and systemic inflammation, and enhancement of the cardiac natriuretic peptide system. The biomarker changes were predominantly mediated by weight loss. [ABSTRACT FROM AUTHOR]

• Analytical performance specifications for hs-cTn assays should be based clinical use. • Outcome studies suggest performance is sufficient for rapid identification of NSTEMI. • Biological variation may guide performance when hs-cTn are used for risk prediction. • Further improvement in analytical performance is likely to be clinically useful. Concurrent with the introduction of cardiac troponin measurements into the diagnostic definition of myocardial infarction (MI), clinicians and laboratory professionals signaled a clear clinical need for improved analytical quality. This was an important precipitant for developing high-sensitivity cardiac troponin (hs-cTn) assays, currently used in rapid algorithms guiding investigations of patients presenting to the emergency department with possible MI. The hs-cTn assays were also important for the detection and monitoring of low-grade chronic myocardial injury, a condition that has been linked to increased long-term risk of cardiovascular morbidity and mortality. This review summarizes the general recommendations for defining analytical performance specifications while providing relevant clinical situations related to analytical performance. Importantly, outcome studies suggest analytical quality performance for hs-cTn is sufficient for early discharge of patients investigated for possible MI. However, bias due to change in calibrators or reagents may significantly affect the percentage of patients discharged. Biological variation data is suitable for defining performance specifications when hs-cTn measurements are used for diagnosing and monitoring chronic myocardial injury. Further improvement in analytical performance for hs-cTn testing may result in even faster decision making in the emergency setting; while also identifying those with chronic injury at risk for an adverse cardiac event. [ABSTRACT FROM AUTHOR]

Background Copeptin concentrations increase both during acute coronary syndrome and following physical exercise. The relationship between copeptin increase following physical exercise and coronary artery disease (CAD) is uncertain. The aim of this study was to 1) describe the copeptin response following strenuous physical exercise, and 2) investigate the determinants of exercise induced copeptin concentrations, particularly in relation to cardiac biomarkers and CAD. Methods Serum samples were collected from 97 recreational cyclists 24 h before, and immediately, 3 and 24 h after a 91-km bike race. Three subjects were subsequently diagnosed with significant asymptomatic CAD. Delta copeptin concentrations were correlated to patient characteristics and to biomarker concentrations. Results Participants were 42.8 ± 9.6 years, and 76.3% were male. Copeptin concentrations increased to maximal levels immediately after the race and were normalized in > 90% after 3 h. A total of 53% and 39% exceeded the 95th and 99th percentile of the assay (10 and 19 pmol/L) respectively. In multivariate models, race time, serum sodium, creatinine and cortisol were significant predictors of copeptin levels. There was no correlation between changes in copeptin and changes in cardiac biomarkers (hs-cTnI, hs-cTnT and BNP). Copeptin concentrations were normal in the subjects with asymptomatic CAD. Conclusions The moderate, short-term, exercise induced copeptin increase observed in the present study was not related to hs-cTn or BNP levels. Copeptin was normal in three asymptomatic recreational athletes with significant CAD. [ABSTRACT FROM AUTHOR]

Objective The European Federation of Laboratory Medicine (EFLM) and the Union of European Medical Specialists (UEMS) joint Working Group on guidelines recently proposed a checklist to help standardize the description of laboratory investigations in clinical practice guidelines (CPG). Methods Nine CPGs or consensus documents published from 2011 to 2013 describing the investigation of chest pain, diagnosis of acute coronary syndrome, or myocardial infarction were evaluated against the published checklist. Results Clinical use of troponin analysis are commonly dealt with but the publications present variable, vague and sometimes conflicting information regarding this laboratory test being very much relied on upon making a diagnosis of acute coronary syndrome. Most of the laboratory related checklist items are not considered or need to be updated e.g. suggested analytical quality goals are not applicable for the high sensitive assays and important interferences that may lead to false positive or negative diagnoses are commonly not mentioned. Conclusion The current paper sums up important analytical and biological issues related to troponin assays and gives suggestions for analytical quality goals that could be included in CPG's. [ABSTRACT FROM AUTHOR]

Background: Correct information provided by guidelines may reduce laboratory test related errors during the pre-analytical, analytical and post-analytical phase and increase the quality of laboratory results. Methods: Twelve clinical practice guidelines were reviewed regarding inclusion of important laboratory investigations. Based on the results and the authors' experience, two checklists were developed: one comprehensive list including topics that authors of guidelines may consider and one consisting of minimal standards that should be covered for all laboratory tests recommended in clinical practice guidelines. The number of topics addressed by the guidelines was related to involvement of laboratory medicine specialists in the guideline development process. Results: The comprehensive list suggests 33 pre- analytical, 37 analytical and 10 post-analytical items. The mean percentage of topics dealt with by the guidelines was 33% (median 30%, range 17%-55%) and inclusion of a laboratory medicine specialist in the guideline committee significantly increased the number of topics addressed. Information about patient status, biological and analytical interferences and sample handling were scarce in most guidelines even if the inclusion of a laboratory medicine specialist in the development process seemingly led to increased focus on, e.g., sample type, sample handling and analytical variation. Examples underlining the importance of including laboratory items are given. Conclusions: Inclusion of laboratory medicine specialist in the guideline development process may increase the focus on important laboratory related items even if this information is usually limited. Two checklists are suggested to help guideline developers to cover all important topics related to laboratory testing. [ABSTRACT FROM AUTHOR]

Reflective testing is a procedure in which the laboratory specialist adds additional tests and/or comments to an original request, after inspection (reflection) of the results. It can be considered as an extension of the authorization process where laboratory tests are inspected before reporting to the physician. The laboratory specialist will inevitably find inconclusive results, and additional testing can contribute to make the appropriate diagnosis. Several studies have been published on the effects of reflective testing. Some studies focus on the opinion of the general practitioners or other clinicians, whereas other studies were intended to determine the patient's perspective. Overall, reflective testing was judged as a useful way to improve the process of diagnosing (and treating) patients. There is to date scarce high quality scientific evidence of the effectiveness of this procedure in terms of patient management. A randomized clinical trial investigating this aspect is however ongoing. Cost effectiveness of reflective testing still needs to be determined in the future. In conclusion, reflective testing can be seen as a new dimension in the service of the clinical chemistry laboratory to primary health care. Additional research is needed to deliver the scientific proof of the effectiveness of reflective testing for patient management. [ABSTRACT FROM AUTHOR]

Background. The aim of this study was to elucidate how laboratory specialists advise clinicians concerning renal parameters and to compare their advice with guideline recommendations. Methods. A questionnaire was distributed to laboratory specialists in Norway and The Netherlands together with two case histories from a primary health-care setting and one from a hospital setting, simulating questions from clinicians. The investigations that laboratory specialists suggested were compared to a test panel that was predefined based on clinical practice guideline recommendations (the 'recommended test panel'). The critical differences between two test results (creatinine, estimated glomerular filtration rate [eGFR] and albumin/creatinine ratio [ACR]) and the anticipated precision of the MDRD equation were evaluated. Results. Fifty-two of the 100 laboratory specialists responded, and most of these were regularly contacted by clinicians to discuss laboratory results. Less than 30% would suggest using the recommended test panel to evaluate renal function in the two primary-care patients. For creatinine and eGFR, median changes stated to signal improvement or deterioration in renal function (creatinine: −14% and ++14%, respectively; eGFR: ++ 18% and −13%, respectively) were similar to what could be calculated using information on analytical and within-subject variation from the literature. There were variable critical differences for the ACR results (median values of −50% for improvement and ++ 67% for deterioration). Only 23% of the participants would recommend a gold standard clearance examination for a patient who was to undergo nephrotoxic chemotherapy. Conclusion. Questions from GPs about renal parameters are answered differently by laboratory specialists, and adherences to guideline recommendations are low on some issues. [ABSTRACT FROM AUTHOR]

Abstract: Background: To explore how CKD stage 3 patients are examined and treated in primary care with emphasis on laboratory analyses. Methods: A total of 386 patients with CKD stage 3, and their physician (one patient per general practitioner (GP)) were selected from hospital laboratory databases. GPs received a questionnaire asking them to categorize their patients'' renal function based on creatinine and eGFR results, denoting follow-up and what changes in creatinine and eGFR results were considered clinically important. Results: The response rate was 60%, and 210 patients were included. Patients'' median creatinine values were 95μmol/L (females) and 124μmol/L (males), the median eGFR value was 52ml/min/1.73m2. Only 27% of patients were assessed to have CKD stage 3. 2/3 had either a urine dip strip (59%) and/or a urine albumin measurement (42%) and 20% were diagnosed with albuminuria. Median changes to signal improvement or deterioration in renal function or indicate referral were 14 (12%), 20 (18%) and 40 (36%)μmol/L for creatinine and 8 (17%), 8 (17%) and 13 (26%)ml/min/1.73m2 for eGFR. Albuminuria did not influence follow-up strategy. Conclusions: CKD stage 3 patients were insufficiently examined for albuminuria and seemingly referred to hospital care after larger eGFR declines than recommended in guidelines. [Copyright &y& Elsevier]

Abstract: Aims: To assess general practitioners (GPs) knowledge of guideline recommendations on diagnosing microalbuminuria (MA) and to evaluate how this diagnosis influences drug treatment of diabetes patients. Methods: A postal case-history based questionnaire describing a male patient (previously not tested for MA) with type 2 diabetes who had several risk markers for cardiovascular disease. Results: 2078GPs from nine European countries were included, with response rates varying from 7% to 43%. Almost all GPs recommended annual testing for MA. Forty-five to 77% (depending on country) of GPs required more than one positive test to diagnose MA. The absolute increase in the percentages of GPs who would supplement the patient''s drug treatment if MA developed was: for anginotensin converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) 23–50% (depending on country), for statins 0–19%, for acetylsalicylic acid 2–13%, and for hypoglycemic agents (tablets and insulin) 0–33%. The proportion of GPs recommending all four possible treatment modalities was low. Conclusions: Guidelines for diagnosing MA were partly followed. ACEIs and ARBs were recommended when MA was present, but the recommended multifactorial treatment of cardiovascular risk markers was not implemented. [Copyright &y& Elsevier]

The relationship between exercise‐induced troponin elevation and non‐obstructive coronary artery disease (CAD) is unclear. This observational study assessed non‐obstructive CAD's impact on exercise‐induced cardiac Troponin I (cTnI) elevation in middle‐aged recreational athletes. cTnI levels of 40 well‐trained recreational athletes (73% males, 50 ± 9 years old) were assessed by a high‐sensitive cTnI assay 24 h before, and at 3 and 24 h following two high‐intensity exercises of different durations; a cardiopulmonary exercise test (CPET), and a 91‐km mountain bike race. Workload was measured with power meters. Coronary computed tomography angiography was used to determine the presence or absence of non‐obstructive (<50% obstruction) CAD. A total of 15 individuals had non‐obstructive CAD (Atherosclerotic group), whereas 25 had no atherosclerosis (normal). There were higher post‐exercise cTnI levels following the race compared with CPET, both at 3 h (77.0 (35.3–112.4) ng/L vs. 11.6 (6.4–22.5) ng/L, p < 0.001) and at 24 h (14.7 (6.7–16.3) vs. 5.0 (2.6–8.9) ng/L, p < 0.001). Absolute cTnI values did not differ among groups. Still, the association of cTnI response to power output was significantly stronger in the CAD versus Normal group both at 3 h post‐exercise (Rho = 0.80, p < 0.001 vs. Rho = −0.20, p = 0.33) and 24‐h post‐exercise (Rho = 0.87, p < 0.001 vs. Rho = −0.13, p = 0.55). Exercise‐induced cTnI elevation was strongly correlated with exercise workload in middle‐aged athletes with non‐obstructive CAD but not in individuals without CAD. This finding suggests that CAD influences the relationship between exercise workload and the cTnI response even without coronary artery obstruction. [ABSTRACT FROM AUTHOR]

Chronic myocardial injury (CMI) is defined as stable concentrations of cardiac troponin T or I (cTnT or cTnI) above the assay-specific 99th percentile upper reference limit (URL) and signals poor outcome. The clinical implications of diagnosing CMI are unclear. We aimed to assess prevalence and association of CMI with long-term prognosis using three different high-sensitivity cTn (hs-cTn) assays. A total of 1,292 hospitalized patients without acute myocardial injury had cTn concentrations quantified by hs-cTn assays by Roche Diagnostics, Abbott Diagnostics and Siemens Healthineers. The median follow-up time was 4.1 years. The prevalence of CMI and hazard ratios for mortality and cardiovascular (CV) events were calculated based on the URL provided by the manufacturers and compared to the prognostic accuracy when lower percentiles of cTn (97.5, 95 or 90), limit of detection or the estimated bioequivalent concentrations between assays were used as cutoff values. There was no major difference in prognostic accuracy between cTnT and cTnI analyzed as continuous variables. The correlation between cTnT and cTnI was high (r=0.724–0.785), but the cTnT assay diagnosed 3.9–4.5 times more patients with having CMI based on the sex-specific URLs (TnT, n=207; TnI Abbott, n=46, TnI Siemens, n=53) and had higher clinical sensitivity and AUC at the URL. The prevalence of CMI is highly assay-dependent. cTnT and cTnI have similar prognostic accuracy for mortality or CV events when measured as continuous variables. However, a CMI diagnosis according to cTnT has higher prognostic accuracy compared to a CMI diagnosis according to cTnI. [ABSTRACT FROM AUTHOR]

The term "single-sample rule-out" refers to the ability of very low concentrations of high-sensitivity cardiac troponin (hs-cTn) on presentation to exclude acute myocardial infarction with high clinical sensitivity and negative predictive value. Observational and randomized studies have confirmed this ability. Some guidelines endorse use of a concentration of hs-cTn at the assay's limit of detection, while other studies have validated the use of higher concentrations, allowing this approach to identify a greater proportion of patients at low risk. In most studies, at least 30% of patients can be triaged with this approach. The concentration of hs-cTn varies according to the assay used and sometimes how regulations permit reporting. It is clear that patients need to be at least 2 hours from the onset of symptoms being evaluated. Caution is warranted, particularly with older patients, women, and patients with underlying cardiac comorbidities. [Display omitted] • Rapid, safe, and accurate exclusion of acute myocardial infarction can facilitate triage of patients in the emergency department. • Observational and randomized studies have found that a single low assay-dependent, hs-cTn measurement taken >2 hours after symptom onset in a patient with a nonischemic electrocardiogram can effectively exclude acute MI. • Additional studies are needed to assess the utility of this approach in patients undergoing evaluation earlier after the onset of symptoms and to establish optimum blood level thresholds for women and patients with specific comorbidities. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Middle- and long-term biological variation data for hematological parameters have been reported in the literature. Within-day 24-h variability profiles for hematological parameters are currently lacking. However, comprehensive hour-to-hour variability data are critical to detect diurnal cyclical rhythms, and to take into account the 'time of sample collection' as a possible determinant of natural fluctuation. In this study, we assessed 24-h variation profiles for 20 hematological parameters. Methods: Blood samples were collected under standardized conditions from 24 subjects every hour for 24 h. At each measurement, 20 hematological parameters were determined in duplicate. Analytical variation (CVA), within-subject biological variation (CVI), between-subject biological variation (CVG), index of individuality (II), and reference change values (RCVs) were calculated. For the parameters with a diurnal rhythm, hour-to-hour RCVs were determined. Results: All parameters showed higher CVG than CVI. Highest CVG was found for eosinophils (46.6%; 95% CI, 34.9%-70.1%) and the lowest value was mean corpuscular hemoglobin concentration (MCHC) (3.2%; 95% CI, 2.4%-4.8%). CVI varied from 0.4% (95% CI, 0.32%-0.42%) to 20.9% (95% CI, 19.4%-22.6%) for red cell distribution width (RDW) and eosinophils, respectively. Six hematological parameters showed a diurnal rhythm. Conclusions: We present complete 24-h variability profiles for 20 hematological parameters. Hour-to-hour reference changes values may help to better discriminate between random fluctuations and true changes in parameters with rhythmic diurnal oscillations. [ABSTRACT FROM AUTHOR]

Sample analysis All serum samples were tested in duplicate on the Erenna SP ® sp platform by EMD Millipore Corporation, Hayward California. However, our CV SB A sb % was obtained from duplicates with median cMyC of 4.38 (2.75-5.97) ng/L, which is considerably lower than median cMyC found in patient with adjudicated diagnosis of acute coronary syndrome 237 (71-876) ng/L in the APACE cohort [[6]], and only ~5% of the 99th percentile (derived from patients without coronary artery disease) [[28]]. Analysis, confined to the initial presentation blood sample, showed that cMyC is at least as good as cardiac troponin measured with the leading assays in predicting the diagnosis of AMI, mortality and future cardiovascular events [[6]]. Keywords: biological variation; cardiac myosin-binding protein C; index of individuality; reference change value EN biological variation cardiac myosin-binding protein C index of individuality reference change value 576 583 8 03/11/22 20220301 NES 220301 Introduction Cardiac myosin-binding protein C (cMyC) is a novel biomarker of myocardial injury that was first identified in cardiac venous effluent approximately 10 years ago [[1]]. [Extracted from the article]

Recommended sample handling and pre-analytical factors that impact the stability of ABG-samples are well documented [[3]] and are likely interchangeable in with VBG-samples if factors related to oxygen stability are ignored. Six out of the eight laboratories with published procedures for VBG-testing opted to use evacuated lithium-heparin tubes instead of recommended air-tight blood gas syringes (BGS), and two out of eight laboratories stored VBG-samples on ice. Accordingly, we undertook a study investigating the stability of the acid/base parameters pH, pCO SB 2 sb , cHCO SB 3 sb SP - sp , and lactate in VBG-samples at room temperature vs. ice and BGS vs. lithium-heparin tubes. [Extracted from the article]

The European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) initiated the CArdiac MARker Guidelines Uptake in Europe (CAMARGUE) Study to survey if current biomarker testing for heart failure (HF) in Europe is in accordance with up-dated guidelines. A web-based questionnaire was distributed to clinical laboratories via European biochemical societies in 2019. Questions covered the type of natriuretic peptide (NP) assays performed, decision limits for HF, and opinion concerning requirement of different thresholds in patients with renal failure or obesity. There were 347 participating laboratories mostly from European countries with 266 offering NP testing. NP testing was increased from 67% to 77% between 2013 and 2019. NT-proBNP remained the preferred biomarker. Recommended decision limits were implemented for BNP (85%) and better focused for NT-proBNP (40%) than in the previous survey. The survey revealed that laboratorians are willing to support the translation of adjusted cut-off values for age, gender and for patients with conditions like renal insufficiency. Guidelines stimulate clinical laboratories to offer NP testing with high value for the diagnosis and management of HF, and to present adjusted medical decision limits. Future guidelines should encourage the use of personalized cut-offs for some confounding factors. [ABSTRACT FROM AUTHOR]

• Harmonization of lipid profiles across European laboratories is poor. • Two-thirds of laboratories use nonfasting lipid measurements. • Less than 50% of laboratories flag guideline-recommended LDLC thresholds. • Less than 50% of laboratories automatically calculate non-HDLC. • Less than one-fourth of laboratories apply alert values for FH. The CArdiac MARker Guidelines Uptake in Europe Study (CAMARGUE) initiated by the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) aims to survey the current use of evidence-based guidelines for dyslipidemia testing in Europe. In 2019 a web-based questionnaire was distributed via EFLM National Societies to clinical laboratories in Europe. Questions covered pre-analytics, analytical methods, measurement units, flagging of decision thresholds, and use of decision-enhancing comments. Returns were obtained from 452 laboratories from 28 countries. Most laboratories always use nonfasting blood samples for lipid assays (66%). Lipid profiles are reported in mmol/L by 59% of the laboratories, mainly from 14 countries promoting the use of SI units. Important differences in flagging of decision thresholds were observed, with less than half of the laboratories applying the guideline-recommended LDL cholesterol threshold. Only 17% of the laboratories add an alert comment when familial hypercholesterolemia is suspected and 23% when risk of pancreatitis from hypertriglyceridemia is high. There are marked differences among laboratories in Europe in terms of pre-analytical, analytical, and post-analytical lipid management that could have an important clinical impact. This relates to different availability of assays or different laboratory practices on reporting and flagging of lipid profiles. [ABSTRACT FROM AUTHOR]

Background: Recent cross‐sectional studies have suggested a dose‐dependent relationship between lifelong exposure to physical activity and the burden of calcified coronary artery disease (CAD). No longitudinal studies have addressed this concern. Hypothesis: Exercise volume is associated with progression of coronary artery calcium (CAC), defined as ≥10 units increase in CAC score. Methods: Sixty‐one recreational athletes who were assessed by coronary computed tomography angiography (CCTA) as part of the NEEDED 2013/14 study were re‐assessed 4‐5 years later, in 2018. Results: Subjects were 45.9 ± 9.6 years old at inclusion, and 46 (74%) were male. Between 2013 and 2018, the participants reported median 5 (range: 0‐20, 25th‐75th percentile: 4‐6) hours of high‐intensity exercise per week. None of the included subjects smoked during follow‐up. At inclusion, 21 (33%) participants had coronary artery calcifications. On follow‐up CCTA in 2018, 15 (25%) subjects had progressive coronary calcification (≥10 Agatston units increase in CAC). These subjects were older (53 ± 9 vs 44 ± 9 years old, P =.002) and had higher levels of low‐density lipoprotein at baseline (3.5 (2.9‐4.3) vs 2.9 (2.3‐3.5) mmol/L, P =.031) as compared to subjects with stable condition. No relationship was found between hours of endurance training per week and progression of coronary artery calcification. In multiple regression analysis, age and baseline CAC were the only significant predictors of progressive CAC. Conclusion: No relationship between exercise training volume and the progression of coronary artery calcification was found in this longitudinal study of middle‐aged recreational athletes. [ABSTRACT FROM AUTHOR]

The joint consensus panel of the European Atherosclerosis Society (EAS) and the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) recently addressed present and future challenges in the laboratory diagnostics of atherogenic lipoproteins. Total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDLC), LDL cholesterol (LDLC), and calculated non-HDLC (=total – HDLC) constitute the primary lipid panel for estimating risk of atherosclerotic cardiovascular disease (ASCVD) and can be measured in the nonfasting state. LDLC is the primary target of lipid-lowering therapies. For on-treatment follow-up, LDLC shall be measured or calculated by the same method to attenuate errors in treatment decisions due to marked between-method variations. Lipoprotein(a) [Lp(a)]-cholesterol is part of measured or calculated LDLC and should be estimated at least once in all patients at risk of ASCVD, especially in those whose LDLC declines poorly upon statin treatment. Residual risk of ASCVD even under optimal LDL-lowering treatment should be also assessed by non-HDLC or apolipoprotein B (apoB), especially in patients with mild-to-moderate hypertriglyceridemia (2–10 mmol/L). Non-HDLC includes the assessment of remnant lipoprotein cholesterol and shall be reported in all standard lipid panels. Additional apoB measurement can detect elevated LDL particle (LDLP) numbers often unidentified on the basis of LDLC alone. Reference intervals of lipids, lipoproteins, and apolipoproteins are reported for European men and women aged 20–100 years. However, laboratories shall flag abnormal lipid values with reference to therapeutic decision thresholds. [ABSTRACT FROM AUTHOR]

The joint consensus panel of the European Atherosclerosis Society (EAS) and the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) recently addressed present and future challenges in the laboratory diagnostics of atherogenic lipoproteins. Total cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, and calculated non-HDL cholesterol (=total – HDL cholesterol) constitute the primary lipid panel for estimating risk of atherosclerotic cardiovascular disease (ASCVD) and can be measured in the nonfasting state. LDL cholesterol is the primary target of lipid-lowering therapies. For on-treatment follow-up, LDL cholesterol shall be measured or calculated by the same method to attenuate errors in treatment decisions due to marked between-method variations. Lipoprotein(a)-cholesterol is part of measured or calculated LDL cholesterol and should be estimated at least once in all patients at risk of ASCVD, especially in those whose LDL cholesterol decline poorly upon statin treatment. Residual risk of ASCVD even under optimal LDL-lowering treatment should be also assessed by non-HDL cholesterol or apolipoprotein B, especially in patients with mild-to-moderate hypertriglyceridemia (2–10 mmol/L). Non-HDL cholesterol includes the assessment of remnant lipoprotein cholesterol and shall be reported in all standard lipid panels. Additional apolipoprotein B measurement can detect elevated LDL particle numbers often unidentified on the basis of LDL cholesterol alone. Reference intervals of lipids, lipoproteins, and apolipoproteins are reported for European men and women aged 20–100 years. However, laboratories shall flag abnormal lipid values with reference to therapeutic decision thresholds. Image 1 • Total cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, and calculated non-HDL cholesterol (=total – HDL cholesterol) constitute the primary lipid panel for estimating risk of atherosclerotic cardiovascular disease (ASCVD) and can be measured in the nonfasting state. • LDL cholesterol is the primary target of lipid-lowering therapies. • Lipoprotein(a)-cholesterol is part of measured or calculated LDL cholesterol and lipoprotein(a) should be measured at least once in all patients. • Residual risk of ASCVD even under optimal LDL-lowering treatment should be also assessed by non-HDL cholesterol or apolipoprotein B, especially in patients with mild-to-moderate hypertriglyceridemia (2-10 mmol/L). • Non-HDL cholesterol includes the assessment of remnant lipoprotein cholesterol and shall be reported in all standard lipid panels. • Laboratories shall flag abnormal lipid values with reference to therapeutic decision thresholds. [ABSTRACT FROM AUTHOR]

Objectives. The main aim of the Aiming toWards Evidence baSed inTerpretation of Cardiac biOmarkers in patients pResenting with chest pain (WESTCOR-study) (Clinical Trials number NCT02620202) is to improve diagnostic pathways for patients presenting to the Emergency department (ED) with acute chest pain. Design. The WESTCOR-study is a two center, cross-sectional and prospective observational study recruiting unselected patients presenting to the ED with suspected non-ST elevation acute coronary syndrome (NSTE-ACS). Patient inclusion started September 2015 and we plan to include 2250 patients, finishing in 2019. The final diagnosis will be adjudicated by two independent cardiologists based on all available information including serial high sensitivity cardiac troponin measurements, coronary angiography, coronary CT angiography and echocardiography. The study includes one derivation cohort (N = 985) that will be used to develop rule out/rule in algorithms for NSTEMI and NSTE-ACS (if possible) using novel troponin assays, and to validate established NSTEMI algorithms, with and without clinical scoring systems. The study further includes one subcohort (n = 500) where all patients are examined with coronary CT angiography independent of biomarker status, aiming to assess the associations between biomarkers and the extent and severity of coronary atherosclerosis. Finally, an external validation cohort (N = 750) will be included at Stavanger University Hospital. Prospective studies will be based on the merged cohorts. Conclusion. The WESTCOR study will provide new diagnostic algorithms for early inclusion and exclusion of NSTE-ACS and insights in the associations between cardiovascular biomarkers, CT-angiographic findings and short and long-term clinical outcomes. [ABSTRACT FROM AUTHOR]

Background The aim of this study was to investigate troponin (cTn) dynamics for both genders, compared the different release patterns to the gender specific 99th percentile and to current biomarker criteria for diagnosing myocardial infarction (MI). Methods Serum was collected from 97 recreational cyclists 24 h before and immediately, 3 and 24 h following a 91-km bike race. hs-cTnI (Abbott) and hs-cTnT (Roche) were measured. Conventional or CT coronary angiography was performed in the 13 participants with the highest hs-cTnI (>140 ng/L). Three subjects with obstructive coronary artery disease were excluded from the statistical analysis. Results There was a significant (p < 0.001) post-race increase in cTnI and cTnT; cTnT peaked immediately, cTnI peaked after 3 h. Relative to the gender specific 99th percentile values, women had the largest increase. The biomarker criteria for MI were met in 76–87% for hs-cTnI, and 96–95% for hs-cTnT (p value <0.05), within the first 3 h post-race. Conclusion Post-race cardiac troponin concentrations exceeded diagnostic criteria for MI in the majority of subjects, more often for hs-cTnT than for hs-cTnI, and more pronounced in women than in men. The current biomarker criteria for MI discriminate poorly between an exercise induced troponin increase and acute MI. [ABSTRACT FROM AUTHOR]

Background: There is increasing interest in direct patient engagement including receiving their laboratory medicine results. We previously established an appetite for Specialists in Laboratory Medicine to support patients in understanding results. The aim of this study was to establish whether patients agreed with such an approach, determined through surveying views in eight European countries. Methods: A standardized five-question survey was administered across eight European countries to a total of 1084 individuals attending medical outpatient clinics, with 100 patients each in Poland, Serbia, Netherlands, Turkey and Czech Republic, 101 in Estonia, 116 in Denmark and 367 in Norway. The responses across countries were compared using the chi-square test (p < 0.05). Results: Patients wanting their results ranged from 50% to 94% (mean 65%) of those responding positively, a mean of 72% wanted additional information with their results; direct receipt was preferred over referral to a website. Specialists in Laboratory Medicine providing such information were acceptable to a mean of 62% of those respondents wishing their results; in countries where payment was possible, there was little interest in making additional payment for such a service. Conclusions: A clear proportion of patients are interested in receiving their laboratory medicine results, the majority with explanatory notes; a role for Specialists in Laboratory Medicine is acceptable and raises the potential for direct engagement by such specialists with patients offering a new paradigm for the provision of laboratory medicine activities. [ABSTRACT FROM AUTHOR]

Introduction: Early rule out of NSTEMI is essential in patients presenting with chest pain. Hypothesis: A novel ultra-sensitive (us) troponin (cTn) assay might have higher diagnostic accuracy compared to high sensitive (hs) cTnT and cTnI assays for early identification of NSTEMI in unselected patients presenting with acute chest pain. Methods: 979 patients admitted to Haukeland University Hospital (Norway) with suspected NSTE-ACS were consecutively included from September 2015 to February 2017. The final diagnosis was adjudicated by two independent cardiologists based on all available clinical, laboratory (i.e. hs-cTnT (Roche Diagnostics)) and imaging data. The samples taken at admission were biobanked and later on also measured for hs-cTnI (Abbott Diagnostics) and a novel ultra sensitive cTnI assay (Singulex Inc. (Sgx)). The following cut off values (i.e. baseline samples taken at admission) was tested for safe rule out of NSTEMI: < 2 ng/L (us-cTnIsgx), < 2 ng/L (hs-cTnIAbbott) and < 5 ng/L (hs-cTnT). The negative predictive value (NPV) for NSTEMI using these cut off values, and the AUC-ROC (Delong test) were compared between the us-cTnIsgx, hs-cTnIAbbott and hs-cTnT assays. Results: The prevalence of NSTEMI was 13%, unstable angina pectoris 11%, non-ACS cardiac disease 8%, non-cardiac chest pain 58% and other diseases 10%. Cardiac troponins were measurable in the baseline sample for 99.9% (us-cTnIsgx), 87% (hs-cTnIAbbott) and 70% (hs-cTnT) of the total cohort, respectively. When we applied the cut off values for rule out as stated above were 0.8% (us-cTnIsgx), 2.3% (hs-cTnIAbbott) and 1.5% (hs-cTnT) of NSTEMI patients incorrectly ruled out. The same cut off values would correctly rule out 51% (us-cTnIsgx), 33% (hs-cTnIAbbott) and 43% (hs-cTnT) of patients with non-cardiac chest pain. The NPV for NSTEMI were 99.7% (us-cTnIsgx), 98.6% (hs-cTnIAbbott) and 99.3% (hs-cTnT). The ROC-AUCs for baseline samples were significantly higher (p value < 0.01) for us-cTnIsgx (AUC 0.95) compared to hs-cTnIAbbott (AUC 0.93) and hs-cTnT (AUC 0.91). Conclusion: The us-cTnIsgx assay showed significant higher diagnostic performance for early rule out of NSTEMI, compared to two commonly used high sensitive troponin assays. [ABSTRACT FROM AUTHOR]