| 1. |
- Kolsrud, Oscar, et al.
(author)
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Measured and not estimated glomerular filtration rate should be used to assess renal function in heart transplant recipients.
- 2016
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In: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. - : Oxford University Press (OUP). - 1460-2385. ; 31:7, s. 1182-9
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Journal article (peer-reviewed)abstract
- In organ transplanted patients, impaired renal function is of major prognostic importance and influences therapeutic decisions. Therefore, monitoring of renal function with glomerular filtration rate (GFR) is of importance, both before and after heart transplantation (HTx). The GFR can be measured directly (mGFR) or estimated (eGFR) with equations based on circulating creatinine or cystatin C levels. However, these equations have not been thoroughly validated in the HTx population.
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| 2. |
- Aakre, K. M., et al.
(author)
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Analytical Considerations in Deriving 99th Percentile Upper Reference Limits for High-Sensitivity Cardiac Troponin Assays: Educational Recommendations from the IFCC Committee on Clinical Application of Cardiac Bio-Markers
- 2022
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In: Clinical chemistry. - : Oxford University Press (OUP). - 0009-9147 .- 1530-8561. ; 68:8, s. 1022-1030
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Journal article (peer-reviewed)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.
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| 3. |
- Aakre, Kristin M, et al.
(author)
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Lower Limits for Reporting High-Sensitivity Cardiac Troponin Assays and Impact of Analytical Performance on Patient Misclassification.
- 2024
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In: Clinical chemistry. - 0009-9147 .- 1530-8561. ; 70:3, s. 497-505
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Journal article (peer-reviewed)abstract
- Cardiac troponin measurements are indispensable for the diagnosis of myocardial infarction and provide useful information for long-term risk prediction of cardiovascular disease. Accelerated diagnostic pathways prevent unnecessary hospital admission, but require reporting cardiac troponin concentrations at low concentrations that are sometimes below the limit of quantification. Whether analytical imprecision at these concentrations contributes to misclassification of patients is debated.The International Federation of Clinical Chemistry Committee on Clinical Application of Cardiac Bio-Markers (IFCC C-CB) provides evidence-based educational statements on analytical and clinical aspects of cardiac biomarkers. This mini-review discusses how the reporting of low concentrations of cardiac troponins impacts on whether or not assays are classified as high-sensitivity and how analytical performance at low concentrations influences the utility of troponins in accelerated diagnostic pathways. Practical suggestions are made for laboratories regarding analytical quality assessment of cardiac troponin results at low cutoffs, with a particular focus on accelerated diagnostic pathways. The review also discusses how future use of cardiac troponins for long-term prediction or management of cardiovascular disease may require improvements in analytical quality.Clinical guidelines recommend using cardiac troponin concentrations as low as the limit of detection of the assay to guide patient care. Laboratories, manufacturers, researchers, and external quality assessment providers should extend analytical performance monitoring of cardiac troponin assays to include the concentration ranges applicable in these pathways.
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| 4. |
- Aldenbratt, Annika, et al.
(author)
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Estimation of kidney function in patients with primary neuromuscular diseases : is serum cystatin C a better marker of kidney function than creatinine?
- 2021
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In: JN. Journal of Nephrology. - : Springer Science and Business Media LLC. - 1121-8428 .- 1724-6059. ; 35:2, s. 493-503
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Journal article (peer-reviewed)abstract
- BACKGROUND: Using serum creatinine leads to an overestimation of kidney function in patients with primary neuromuscular disorders, and reduced kidney function may remain undetected. Cystatin C (CysC) could provide a better estimation.AIM: To evaluate the precision, accuracy, and bias of two creatinine-, one cystatin C-based and one combined equation to estimate glomerular filtration rate (eGFR) in patients with primary neuromuscular disease.PATIENTS AND METHODS: Of the 418 patients initially identified at the out-patient clinic, data on kidney function was obtained for 145 adult patients (age 46 ± 14 years, BMI 26 ± 6 kg/m2) with primary neuromuscular disease. Kidney function was measured by iohexol clearance, and blood samples for serum creatinine and CysC were drawn simultaneously. Bias was defined as the mean difference between eGFR and measured iohexol clearance, and accuracy as the proportion of eGFRs within ± 10% (P10) of measured clearance.RESULTS: Kidney function (iohexol clearance) was 81 ± 19 (38-134) ml/min/1.73m2. All equations overestimated kidney function by 22-60 ml/min/1.73m2. eGFR CysC had the lowest bias overall 22 (95% CI 20-26) ml/min/1.73m2 also at all levels of kidney function we evaluated (at 30-59 ml/min/1.73m2 bias was 27 (95% CI 21-35), at 60-89 it was 25 (95% CI 20-28) and at ≥ 90 it was 12 (95% CI 7-22)). eGFR CysC also had the best accuracy in patients with reduced kidney function (P10 was 5.9% at 30-59 ml/min/1.73m2).CONCLUSIONS: Cystatin C-based estimations of kidney function performed better than creatinine-based ones in patients with primary neuromuscular disease, but most importantly, all evaluated equations overestimated kidney function, especially in patients with reduced kidney function. Therefore, kidney function should be measured by gold-standard methods when precision and accuracy are needed.
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| 5. |
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| 6. |
- Bergström, Petra, et al.
(author)
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Association of NFE2L2 and KEAP1 haplotypes with amyotrophic lateral sclerosis.
- 2014
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In: Amyotrophic lateral sclerosis & frontotemporal degeneration. - : Informa UK Limited. - 2167-9223 .- 2167-8421. ; 15:1-2, s. 130-137
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Journal article (peer-reviewed)abstract
- Amyotrophic lateral sclerosis (ALS) is a degenerative motor neuron syndrome influenced by oxidative stress. The transcription factor Nrf2 and its repressor Keap1 constitute an important defence system in cellular protection against oxidative stress. Here we hypothesize that common genetic variations in the genes NFE2L2 and KEAP1, encoding Nrf2 and Keap1, may influence the risk and phenotype of ALS. Five hundred and twenty-two Swedish patients with sporadic ALS (SALS) and 564 Swedish control subjects were studied. Eight tag SNPs in NFE2L2 and three tag SNPs in KEAP1 were genotyped by allelic discrimination and three functional NFE2L2 promoter SNPs were genotyped by sequencing. One NFE2L2 haplotype (GGGAC) was associated with decreased risk of SALS (OR = 0.62 per allele, p = 0.003) and one haplotype in KEAP1 (CGG) was associated with later SALS onset (+3.4 years per allele, p = 0.015). When stratified by subgroup, one haplotype in NFE2L2, GAGCAGA including three functional promoter SNPs associated with high Nrf2 protein expression, was associated with 4.0 years later disease onset per allele in subgroup ALS (p = 0.008). In conclusion, these results suggest that variations in NFE2L2 and KEAP1, encoding two central proteins in cellular oxidative stress defence, may influence SALS pathogenesis.
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| 7. |
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| 8. |
- Bjurman, Christian, 1983, et al.
(author)
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Assessment of a multi-marker risk score for predicting cause-specific mortality at three years in older patients with heart failure and reduced ejection fraction.
- 2015
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In: Cardiology journal. - 1897-5593. ; 22:1, s. 31-6
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Journal article (peer-reviewed)abstract
- Due to increasing co-morbidity associated with aging, heart failure (HF) has become more prevalent and heterogeneous in older individuals, and non-cardiovascular (CV) mortality has increased. Previously, we defined a multi-marker modality that included cystatin C (CysC), troponin T (TnT), and age. Here, we validated this multi-marker risk score by evaluating its predictions of all-cause mortality and CV mortality in an independent population of older individuals with HF and reduced ejection fraction (HFrEF).
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| 9. |
- Bjurman, Christian, 1983, et al.
(author)
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Assessment of a multimarker strategy for prediction of mortality in older heart failure patients: a cohort study
- 2013
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In: BMJ open. - : BMJ. - 2044-6055. ; 3:3
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Journal article (peer-reviewed)abstract
- OBJECTIVE: Primarily to develop a multimarker score for prediction of 3-year mortality in older patients with decompensated heart failure (HF). DESIGN: Prospective cohort study. SETTING: Secondary care. Single centre. PATIENTS AND BIOMARKERS: 131 patients, aged >/=65 years, with decompensated HF were included. Assessment of biomarkers was performed at discharge. PRIMARY OUTCOME MEASURE: 3-year mortality. RESULTS: Mean age was 73+/-11 years; mean left ventricular ejection fraction , 43+/-14%; 53% were male. The 3-year mortality was 53.4%. The following N-terminal brain natriuretic peptide (NTproBNP) levels could optimally stratify mortality: <2000 ng/l (n=39), 30.8% mortality; 2000-8000 ng/l (n=58), 51.7% mortality; and >8000 ng/l (n=34), 82.4% mortality. However, in the 2000-8000 ng/l range, NTproBNP levels had low-prognostic capacity, based on the area under the receiver operating characteristic curve (AUC=0.53; 95% CI 0.40 to 0.67). In this group, multivariate analysis identified age, cystatin C (CysC), and troponin T (TnT) levels as independent risk factors. A risk score based on these three risk factors separated a high-risk and low-risk groups within the NTproBNP range of 2000-8000 ng/l. The score exhibited a significantly higher AUC (0.75; 95% CI 0.62 to 0.86) than NTproBNP alone (p=0.03) in this NTproBNP group and had similar prognostic capacity as NTproBNP in patients below or above this NTproBNP range (p=0.57). Net reclassification improvement and integrated discriminatory improvement in the group with NTproBNP levels between 2000 and 8000 ng/l was 54% and 23%, respectively, and in the whole cohort 22% and 11%, respectively. CONCLUSIONS: Our results suggested that, to assess risk in HF, older patients required significantly higher levels of NTproBNP than younger patients. Furthermore, a risk score that included TnT and CysC at discharge, and age could improve risk stratification for mortality in older patients with HF in particular when NTproBNP was moderately elevated.
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| 10. |
- Bjurman, Christian, 1983, et al.
(author)
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Cystatin C in a composite risk score for mortality in patients with infective endocarditis: a cohort study
- 2012
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In: BMJ open. - : BMJ. - 2044-6055. ; 2:4
-
Journal article (peer-reviewed)abstract
- OBJECTIVE: To develop a multimarker prognostic score for infective endocarditis (IE). DESIGN: Retrospective case-control. SETTING: Secondary care. Single centre. PARTICIPANTS: 125 patients with definite IE. PRIMARY OUTCOME MEASURES: 90-day and 5-year mortality. RESULTS: Mean age was 62.7+/-17 years. The 90-day and 5-year mortality was 10.4% and 33.6%, respectively. CysC levels at admission and over 20% increases in CysC levels during 2 weeks of treatment were prognostic for 90-day and 5-year mortality independent of creatinine estimated glomerular filtration rate. In multivariate analyses, CysC (OR 5.42, 95% CI 1.90 to 15.5, p=0.002) and age (OR 1.06, 95% CI 1.02 to 1.10, p=0.002) remained prognostic for 5-year mortality. NT-proBNP, TnT, C reactive protein and interleukin 6 were also linked to prognosis. A composite risk scoring system using levels of CysC, NT-proBNP, age and presence of mitral valve insufficiency was able to separate a high-risk and a low-risk group. CONCLUSIONS: CysC levels at admission and increase in CysC after 2 weeks of treatment were independent prognostic markers for both 90-day and 5-year mortality in patients with IE. A multimarker composite risk scoring system including CysC identified a high-risk group.
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| 11. |
- Bjurman, Christian, 1983, et al.
(author)
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Decreased admissions and hospital costs with a neutral effect on mortality following lowering of the troponin T cutoff point to the 99th percentile
- 2017
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In: Cardiology journal. - 1897-5593 .- 1898-018X. ; 24:6, s. 612-622
-
Journal article (peer-reviewed)abstract
- Background: The implementation of high-sensitivity cardiac troponin T (hs-cTnT) assays and a cutoff based on the 99th cTnT percentile in the evaluation of patients with suspected acute coronary syndrome has not been uniform due to uncertain effects on health benefits and utilization of limited resources.Methods:Clinical and laboratory data from patients with chest pain or dyspnea at the emergency department (ED) were evaluated before (n = 20516) and after (n = 18485) the lowering of the hs-cTnT cutoff point from 40 ng/L to the 99th hs-cTnT percentile of 14 ng/L in February 2012. Myocardial infarction (MI) was diagnosed at the discretion of the attending clinicians responsible for the patient.Results:Following lowering of the hs-cTnT cutoff point fewer ED patients with chest pain or dyspnea as the principal complaint were analyzed with an hs-cTnT sample (81% vs. 72%, p < 0.001). Overall 30-day mortality was unaffected but increased among patients not analyzed with an hs-cTnT sample (5.3% vs. 7.6%, p < 0.001). The MI frequency was unchanged (4.0% vs. 3.9%, p = 0.72) whereas admission rates decreased (51% vs. 45%, p < 0.001) as well as hospital costs. Coronary angiographies were used more frequently (2.8% vs. 3.3%, p = 0.004) but with no corresponding change in coronary interventions.Conclusions:At the participating hospital, lowering of the hs-cTnT cutoff point to the 99th percentile decreased admissions and hospital costs but did not result in any apparent prognostic or treatment benefits for the patients.
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| 12. |
- Bjurman, Christian, 1983, et al.
(author)
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High-sensitive cardiac troponin, NT-proBNP, hFABP and copeptin levels in relation to glomerular filtration rates and a medical record of cardiovascular disease
- 2015
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In: Clinical Biochemistry. - : Elsevier BV. - 0009-9120 .- 1873-2933. ; 48:4-5, s. 302-307
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Journal article (peer-reviewed)abstract
- Background: Elevation of cardiac markers in patients with renal dysfunction has not been fully assessed reducing the diagnostic usefulness of these biomarkers. Objective: To examine the effects of renal function and a medical record of cardiovascular disease on levels of cardiac biomarkers. Methods: Serum samples were collected from 489 patients referred for GFR measurement using Cr51-EDTA or iohexol plasma clearance (measured GFR). The cardiac biomaiters Troponin T (hs-cTnT), Troponin I (hsTnI), N-Terminal pro Brain Natriuretic Peptide (NTproBNP), Copeptin, Human Fatty Acid Binding Protein (hFABP), as well as the kidney function biomarkers creatinine and cystatin C, were measured. Regression was used to analyse the relationship between biomarker levels and the glomerular filtration rate (GFR) between 15 and 90 mL/min/1.73 m(2). Results: Compared with normal kidney function, the estimated increases in the studied cardiac biomarkers at a CUR of 15 mL/mM/1.73 m(2) varied from 2-fold to 15 fold but were not very different between patients with or without a medical record of cardiovascular disease and were most prominent for cardiac biomarkers with low molecular weight. hs-cTnT levels correlated more strongly to measured CUR and increased more at low CUR compared to hs-cTnI. For hFABP and NT-proBNP increases at low kidney function were more correctly predicted by a local Cystatin C-based eGFR formula compared with creatinine-based eGFR (using the MDRD or CKD-EPI equations) Conclusion: The extent of the elevation of cardiac markers at low renal function is highly variable. For hFABP and NTproBNP Cystatin C-based eGFR provides better predictions of the extent of elevation compared to the MDRD or CKD-EPI equations. (C) 2015 The Authors. The Canadian Society of Clinical Chemists. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd,40/).
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| 13. |
- Bjurman, Christian, 1983, et al.
(author)
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Patients discharged with elevated baseline high-sensitive cardiac troponin T from the emergency department
- 2021
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In: Biomarkers. - : Informa UK Limited. - 1354-750X .- 1366-5804. ; 26:5, s. 410-416
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Journal article (peer-reviewed)abstract
- Background Elevated levels of high-sensitive cardiac troponin T (hs-cTnT) are linked to poor prognosis among emergency department (ED) patients. Objective Examine the effect of our ED risk assessment among patients with suspected acute coronary syndrome (ACS) and elevated baseline hs-cTnT levels. Design Observational cohort study of 16776 ED patients with chest pain or dyspnoea and a hs-cTnT sample analyzed at the time of the ED visit. Of these 1480 patients were sent home with elevated hs-cTnT levels (>14 ng/L). Methods Analysis of clinical and laboratory data from the local hospital and data from the National Board of Health and Welfare. Results Admitted patients had 11% and discharged patients had 1.2% 90-day mortality indicating effective risk assessment of patients with suspected ACS. However, if the suspected ACS patient presented with hs-cTnT between 14 and 22 ng/L, the 90-day mortality was 4.1% among discharged and 6.7% among admitted patients. Among discharged patients, an hs-cTnT level above 14 ng/L was a higher independent risk factor for 90-day mortality (HR 3.3, 95% CI 2.9-3.7, p < 0.001) than if the patient was triaged as a high-risk patient (HR 1.6, 95% CI 1.1-1.8, p < 0.001). Conclusions Our ED risk assessment was less effective among patients presenting with elevated hs-cTnT levels.
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| 14. |
- Bjurman, Christian, 1983, et al.
(author)
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Small changes in Troponin T levels are common in patients with non-ST-elevation myocardial infarction and are linked to higher mortality
- 2013
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In: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 62:14, s. 1231-1238
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Journal article (peer-reviewed)abstract
- OBJECTIVE:To examine the extent of change in Troponin T levels in patients with non-ST-elevation myocardial infarction (NSTEMI).BACKGROUND:Changes in cardiac troponin levels are required for the diagnosis of NSTEMI, according to the new universal definition of acute myocardial infarction. A relative change of 20-230 % and an absolute change of 7- 9 ng/L have been suggested as cut-off points.METHOD:In a clinical setting, where a change in cTnT was not mandatory for the diagnosis of NSTEMI, serial samples of cTnT were measured with a high-sensitive cTnT (hs-cTnT) assay, and 37 clinical parameters were evaluated in 1178 patients with a final diagnosis of NSTEMI presenting <24h after symptom onset.RESULTS:After six hours of observation, the relative change in the hs-cTnT level remained <20 % in 26 % and the absolute change <9 ng/L in 12 % of the NSTEMI patients. A relative hs-cTnT change <20% was linked to higher long-term mortality across quartiles (p=0.002) and in multivariate analyses (HR 1.61 (1.17-2.21) p=0.004), whereas 30-day mortality was similar across quartiles of relative hs-cTnT changeCONCLUSION:Because stable hs-TnT levels are common in patients with a clinical diagnosis of NSTEMI in our hospital, a small hs-cTnT change may not be useful to exclude NSTEMI, particularly as these patients show both short-term and long-term mortality at least as high as patients with large changes in hs-cTnT.
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| 15. |
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| 16. |
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| 17. |
- Carlsson, Axel C., et al.
(author)
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High-sensitivity cardiac troponin T levels in the emergency department in patients with chest pain but no myocardial infarction
- 2017
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In: International Journal of Cardiology. - : ELSEVIER IRELAND LTD. - 0167-5273 .- 1874-1754. ; 228, s. 253-259
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Journal article (peer-reviewed)abstract
- Background: High-sensitivity cardiac troponin T (hs-cTnT) was recently introduced into clinical practice. The increased sensitivity has decreased the specificity. We aimed to determine the predictors for and prevalence of hs-cTnT levels above the 99th percentile in a stable population of patients without myocardial infarction (MI) who sought medical attention for chest pain in the emergency department. Methods: We included 11,847 patients with chest pain and at least one hs-cTnT measurement during 2011 and 2012. Patients with any acute reasons for an elevated hs-cTnT level were excluded. We used logistic regression to calculate adjusted odds ratios with 95% confidence intervals for the association between patient characteristics and hs-cTnT levels of >14 ng/L. We also determined 50th, 75th, 97.5th, and 99th percentile values of hs-cTnT levels in relation to age, sex, estimated glomerular filtration rate (eGFR), and presence or absence of comorbidities. Results: In total, 1360 (11%) patients had hs-cTnT levels of >14 ng/L. Men had higher troponin levels than women, and older patients had higher levels than younger patients. The strongest predictor of an elevated troponin level was a reduced eGFR. The 99th percentile for hs-cTnT among all men and among women <50 years of age with normal renal function was 20 and 12 ng/L, respectively; this level increased to 44 and 36 ng/L, respectively, at the age of 70-79 years. Conclusions: A hs-cTnT level above the 99th percentile in patients with chest pain but no MI is common and is related to sex, age, and eGFR.
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| 18. |
- Collinson, P., et al.
(author)
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Cardiac troponin measurement at the point of care: educational recommendations on analytical and clinical aspects by the IFCC Committee on Clinical Applications of Cardiac Bio-Markers (IFCC C-CB)
- 2023
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In: Clinical Chemistry and Laboratory Medicine. - : Walter de Gruyter GmbH. - 1434-6621 .- 1437-4331. ; 61:6, s. 989-998
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Journal article (peer-reviewed)abstract
- 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.
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| 19. |
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| 20. |
- DuttaRoy, Smita, 1971, et al.
(author)
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High frequency home-based exercise decreases levels of vascular endothelial growth factor in patients with stable angina pectoris.
- 2015
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In: European Journal of Preventive Cardiology. - : Oxford University Press (OUP). - 2047-4873 .- 2047-4881. ; 22:5, s. 575-581
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Journal article (peer-reviewed)abstract
- In coronary artery disease (CAD), circulating angiogenic factors have been seen to increase, possibly as a response to ischaemia. Regular physical activity (PA) is recommended for prevention and treatment of CAD, but more research is needed to optimise PA regimes. We investigated the effect of home-based high frequency exercise (HFE) on angiogenic cytokines and cardiac markers in patients with stable CAD.
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| 21. |
- DuttaRoy, Smita, 1971, et al.
(author)
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The effects of age on circulating vascular markers and cardiac prognostic markers, before and after 2 months home-based high-frequency exercise training in patients with stable coronary artery disease
- 2014
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In: European Heart Journal. European Society of Cardiology, 30 August - 3 September 2014, Barcelona. - 0195-668X .- 1522-9645. ; 35:Supplement: 1
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Conference paper (other academic/artistic)abstract
- Purpose: Vascular endothelial growth factor (VEGF) and stromal derived factor (SDF-1) play an important role in angiogenesis. Relaxin-2 (Rlx-2) has both angiogenic and vasodilatory properties, while endothelin-1 (ET-1) is a potent vasocontrictor.VEGF, SDF-1 and Rlx-2-levels have shown to be positively modulated by exercise training, while the effect of exercise on (Rlx-2) is not known. Age is a known risk factor for morbidity and mortality in coronary artery disease (CAD). We wanted to investigate how age affects levels of these vascular factors and known prognostic cardiac markers before and after high frequency exercise training (HFE), in patients with CAD. Methods: Patients with stable CAD (age 48-80 years) were randomized to HFE (aerobic exercise 70% of max, 30 minutes, 5 times/week and resistance exercise 3 times/week), performed at home for 8 weeks, or usual lifestyle (ctrl). Serum and plasma was collected from 21 controls and 24 HFE-patients and analyzed at baseline and after 8 weeks. VEGF, SDF-1, Rlx-2 and ET-1were analyzed with enzymelinked immunoadsorbent assay (ELISA). TnT and NT-pro-BNP were analyzed on Cobas e602 (Roche). Correlation was calculated using the statistical software Graph Pad Prism 6. Pearson’s r was calculated to determine correlation between the factors prior to exercise, while Spearman’s r was used for the analysis on the exercise induced effects of the HFE-group. The exercise-induced effect on cardiac biomarkers was determined by comparing % change (from baseline to 8 weeks) between HFE and Ctrl using Mann-Whitney U-test. Results: At baseline, there was a significant positive correlation between age and TnT (r=0.38, p<0.05) and a non-significant positive correlation between age and NT-proBNP (r=0.36, p=0.06), while no correlation was found between age and levels of vascular markers (VEGF r=-0,14, SDF-1 r=-0,13, ET-1 r=0,08, Rlx-2 r=0,06, p=ns for all). As we have previously shown, home-based HFE decreased VEGF (2,6+29% (ctrl) and -3,9 +13% (HFE), p<0,05), but the other studied factors were not significantly affected. We found no correlation between age and changes in cardiac markers after exercise. Conclusions: Elderly patients with stable CAD have higher levels of TnT and NT-proBNP, indicating a higher degree of underlying CAD. This may also reflect their higher mortality in CAD. HFE-training may lower VEGF in patients with stable CAD. Interestingly, there seems to be no difference in the respone response to exercise in cardiac biomarkers, between younger and older CAD patients
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| 22. |
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| 23. |
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| 24. |
- Eggers, Kai M., 1962-, et al.
(author)
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Diagnostic and prognostic performance of the ratio between high-sensitivity cardiac troponin I and troponin T in patients with chest pain
- 2022
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 17:11
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Journal article (peer-reviewed)abstract
- Background Elevations of high-sensitivity cardiac troponin (hs-cTn) concentrations not related to type 1 myocardial infarction are common in chest pain patients presenting to emergency departments. The discrimination of these patients from those with type 1 myocardial infarction (MI) is challenging and resource-consuming. We aimed to investigate whether the hs-cTn I/T ratio might provide diagnostic and prognostic increment in this context.Methods We calculated the hs-cTn I/T ratio in 888 chest pain patients having hs-cTnI (Abbott Laboratories) or hs-cTnT (Roche Diagnostics) concentrations above the respective 99(th) percentile at 2 hours from presentation. All patients were followed for one year regarding mortality.Results The median hs-cTn I/T ratio was 3.45 (25(th), 75(th) percentiles 1.80-6.59) in type 1 MI patients (n = 408 (sic) 46.0%]), 1.18 (0.81-1.90) in type 2 MI patients (n = 56 (sic) 6.3%]) and 0.67 (0.39-1.12) in patients without MI. The hs-cTn I/T ratio provided good discrimination of type 1 MI from no type 1 MI (area under the receiver-operator characteristic curve 0.89 (sic) 95% confidence interval 0.86-0.91]), of type 1 MI from type 2 MI (area under the curve 0.81 (sic) 95% confidence interval 0.74-0.87]), and was associated with type 1 MI in adjusted analyses. The hs-cTn I/T ratio provided no consistent prognostic value.Conclusions The hs-cTn I/T ratio appears to be useful for early diagnosis of type 1 MI and its discrimination from type 2 MI in chest pain patients presenting with elevated hs-cTn. Differences in hs-cTn I/T ratio values may reflect variations in hs-cTn release mechanisms in response to different types of myocardial injury.
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| 25. |
- Eggers, Kai M., 1962-, et al.
(author)
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Diagnostic and prognostic performance of the ratio between high-sensitivity cardiac troponin I and troponin T in patients with chest pain.
- 2022
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In: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 17:11
-
Journal article (peer-reviewed)abstract
- Elevations of high-sensitivity cardiac troponin (hs-cTn) concentrations not related to type 1 myocardial infarction are common in chest pain patients presenting to emergency departments. The discrimination of these patients from those with type 1 myocardial infarction (MI) is challenging and resource-consuming. We aimed to investigate whether the hs-cTn I/T ratio might provide diagnostic and prognostic increment in this context.We calculated the hs-cTn I/T ratio in 888 chest pain patients having hs-cTnI (Abbott Laboratories) or hs-cTnT (Roche Diagnostics) concentrations above the respective 99th percentile at 2 hours from presentation. All patients were followed for one year regarding mortality.The median hs-cTn I/T ratio was 3.45 (25th, 75th percentiles 1.80-6.59) in type 1 MI patients (n = 408 ☯46.0%]), 1.18 (0.81-1.90) in type 2 MI patients (n = 56 ☯6.3%]) and 0.67 (0.39-1.12) in patients without MI. The hs-cTn I/T ratio provided good discrimination of type 1 MI from no type 1 MI (area under the receiver-operator characteristic curve 0.89 ☯95% confidence interval 0.86-0.91]), of type 1 MI from type 2 MI (area under the curve 0.81 ☯95% confidence interval 0.74-0.87]), and was associated with type 1 MI in adjusted analyses. The hs-cTn I/T ratio provided no consistent prognostic value.The hs-cTn I/T ratio appears to be useful for early diagnosis of type 1 MI and its discrimination from type 2 MI in chest pain patients presenting with elevated hs-cTn. Differences in hs-cTn I/T ratio values may reflect variations in hs-cTn release mechanisms in response to different types of myocardial injury.
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| 26. |
- Eggers, Kai M., 1962-, et al.
(author)
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Differences between high-sensitivity cardiac troponin T and I in stable populations : underlying causes and clinical implications
- 2023
-
In: Clinical Chemistry and Laboratory Medicine. - : Walter de Gruyter. - 1434-6621 .- 1437-4331. ; 61:3, s. 380-387
-
Journal article (peer-reviewed)abstract
- ObjectivesMeasurement of high-sensitivity (hs) cardiac troponin (cTn) T and I is widely studied for cardiac assessment of stable populations. Recent data suggest clinical and prognostic discrepancies between both hs-cTn. We aimed at reviewing published studies with respect to underlying causes and clinical implications.ContentWe summarized current evidence on release and clearance mechanisms of cTnT and I, and on preanalytical and assay-related issues potentially portending to differences in measured concentrations. We also performed a systematic review of outcome studies comparing both hs-cTn in the general population, patients with congestive heart failure, stable coronary artery disease and atrial fibrillation.Summary and outlookFor the interpretation of concentrations of hs-cTnT, stronger association with renal dysfunction compared to hs-cTnI should be considered. Hs-cTnT also appears to be a stronger indicator of general cardiovascular morbidity and all-cause mortality. Hs-cTnI concentrations tend to be more sensitive to coronary artery disease and ischemic outcomes. These findings apparently reflect variations in the mechanisms of cardiac affections resulting in cTn release. Whether these differences are of clinically relevance remains to be elucidated. However, having the option of choosing between either hs-cTn might represent an option for framing individualized cardiac assessment in the future.
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| 27. |
- Eggers, Kai M., 1962-, et al.
(author)
-
Differences between high-sensitivity cardiac troponin T and I in stable populations: underlying causes and clinical implications.
- 2023
-
In: Clinical chemistry and laboratory medicine. - : Walter de Gruyter GmbH. - 1434-6621 .- 1437-4331. ; 61:3, s. 380-387
-
Journal article (peer-reviewed)abstract
- Measurement of high-sensitivity (hs) cardiac troponin (cTn) T and I is widely studied for cardiac assessment of stable populations. Recent data suggest clinical and prognostic discrepancies between both hs-cTn. We aimed at reviewing published studies with respect to underlying causes and clinical implications.We summarized current evidence on release and clearance mechanisms of cTnT and I, and on preanalytical and assay-related issues potentially portending to differences in measured concentrations. We also performed a systematic review of outcome studies comparing both hs-cTn in the general population, patients with congestive heart failure, stable coronary artery disease and atrial fibrillation.For the interpretation of concentrations of hs-cTnT, stronger association with renal dysfunction compared to hs-cTnI should be considered. Hs-cTnT also appears to be a stronger indicator of general cardiovascular morbidity and all-cause mortality. Hs-cTnI concentrations tend to be more sensitive to coronary artery disease and ischemic outcomes. These findings apparently reflect variations in the mechanisms of cardiac affections resulting in cTn release. Whether these differences are of clinically relevance remains to be elucidated. However, having the option of choosing between either hs-cTn might represent an option for framing individualized cardiac assessment in the future.
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| 28. |
- Elmroth, Kerstin, 1970, et al.
(author)
-
Cleavage of cellular DNA by calicheamicin γ1
- 2003
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In: DNA Repair. - 1568-7864 .- 1568-7856. ; 2:4, s. 363-374
-
Journal article (peer-reviewed)abstract
- It is assumed that the efficient antitumor activity of calicheamicin γ1 is mediated by its ability to introduce DNA double-strand breaks in cellular DNA. To test this assumption we have compared calicheamicin γ1-mediated cleavage of cellular DNA and purified plasmid DNA. Cleavage of purified plasmid DNA was not inhibited by excess tRNA or protein indicating that calicheamicin γ1 specifically targets DNA. Cleavage of plasmid DNA was not affected by incubation temperature. In contrast, cleavage of cellular DNA was 45-fold less efficient at 0°C as compared to 37° due to poor cell permeability at low temperatures. The ratio of DNA double-strand breaks (DSB) to single-stranded breaks (SSB) in cellular DNA was 1:3, close to the 1:2 ratio observed when calicheamicin γ1 cleaved purified plasmid DNA. DNA strand breaks introduced by calicheamicin γ1 were evenly distributed in the cell population as measured by the comet assay. Calicheamicin γ1-induced DSBs were repaired slowly but completely and resulted in high levels of H2AX phosphorylation and efficient cell cycle arrest. In addition, the DSB-repair deficient cell line Mo59J was hyper sensitive to calicheamicin γ. The data indicate that DSBs is the crucial damage after calicheamicin γ1 and that calicheamicin γ1-induced DSBs are recognized normally. The high DSB:SSB ratio, specificity for DNA and the even damage distribution makes calicheamicin γ1 a superior drug for studies of the DSB-response and emphasizes its usefulness in treatment of malignant disease.
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| 29. |
- Erlandsson, A C, et al.
(author)
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Herpes simplex virus type 1 infection and glucocorticoid treatment regulate viral yield, glucocorticoid receptor and NF-kappaB levels.
- 2002
-
In: The Journal of endocrinology. - : Bioscientifica. - 0022-0795 .- 1479-6805. ; 175:1, s. 165-76
-
Journal article (peer-reviewed)abstract
- The interplay between the endocrine and immune systems has come into focus in recent years with the insight that endocrine parameters may affect susceptibility to both auto-immune and infectious diseases. Our interest in immunoendocrine regulation led us to investigate the effects of glucocorticoids on Herpes simplex virus type 1 (HSV-1) infections. Glucocorticoids used to treat inflammatory conditions are not yet recommended for HSV-1 therapy, since they have been reported to prolong viral shedding both in vivo and in vitro. Here we report that glucocorticoids did not alter the viral yield in human gingival fibroblast (HGF) cell culture when glucocorticoid treatment and viral infection occured simultaneously, but the viral yield increased when cells were treated with the glucocorticoid dexamethasone (dex) prior to viral infection. We found that viral infection in our primary cell system increased NF-kappaB levels and DNA binding. In addition, the amount of glucocorticoid receptor (GR) increased following viral infection, and HSV-1 infection as such could induce glucocorticoid-driven transcription of a reporter gene in human embryo kidney (HEK) 293 cells stably transfected with GR. Dex treatment did not affect HSV-1-induced binding of p65 to an NF-kappaB element in an electrophoretic mobility shift assay, and acyclovir was still efficient as an anti-viral drug in the presence of dex. Further studies of the observed effects of HSV-1 infection and glucocorticoid treatment on GR and NF-kappaB regulation could give insights into the immunoendocrine mechanisms important for defence and therapy against viral infections.
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| 30. |
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| 31. |
- Fridén, Vincent, 1975, et al.
(author)
-
Clearance of cardiac troponin T with and without kidney function
- 2017
-
In: Clinical Biochemistry. - : Elsevier BV. - 0009-9120. ; 50:9, s. 468-474
-
Journal article (peer-reviewed)abstract
- Objective: The extent of kidney-dependent clearance of the cardiac damage biomarker cardiac troponin T (cTnT) is not known. Methods and results: We examined clearance of cTnT after injection of heart extracts in rats with or without clamped kidney vessels. The extent of degradation of cTnT to fragments able to pass the glomerular membrane and the kidney extraction index of cTnT was examined in human subjects. After a bolus injection of rat cardiac extract, simulating a large myocardial infarction, there was no significant difference in clearance of cTnT with or without kidney function. However, a slower clearance was observed late in the clearance process, when cTnT levels were low. When low levels of rat cardiac extract were infused at a constant rate to steady state, clamping of the renal vessels resulted in significant 2-fold reduction in clearance of cTnT. Over 60% of the measured cTnT in human subjects had a molecular weight below 17 kDa, expected to have a relatively free passage over the glomerular membrane. The extraction index of cTnT in three heart failure patients undergoing renal vein catheterization was 8-19%. Kidney function adjusted cTnT levels increased the area under the ROC curve for diagnosis of myocardial infarction of the cTnT analysis in an emergency room cohort. Conclusions: At high concentrations, often found after a large myocardial infarction, extrarenal clearance of cTnT dominates. At low levels of cTnT, often found in patients with stable cTnT elevations, renal clearance also contribute to the clearance of cTnT. This potentially explains why stable cTnT levels tend to be higher in patients with low kidney function. (C) 2017 Published by Elsevier Inc. on behalf of The Canadian Society of Clinical Chemists.
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| 32. |
- Grankvist, Kjell, et al.
(author)
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Laboratoriernas verksamhet
- 2018. - 10
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In: Laurells Klinisk kemi i praktisk medicin. - Lund : Studentlitteratur AB. - 9789144119748 ; , s. 13-30
-
Book chapter (peer-reviewed)
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| 33. |
- Hammarsten, Ola, et al.
(author)
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Antibody-mediated interferences affecting cardiac troponin assays: recommendations from the IFCC Committee on Clinical Applications of Cardiac Biomarkers
- 2023
-
In: CLINICAL CHEMISTRY AND LABORATORY MEDICINE. - : Walter de Gruyter GmbH. - 1434-6621 .- 1437-4331. ; 61:8
-
Journal article (peer-reviewed)abstract
- 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.
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| 34. |
- Hammarsten, Ola, et al.
(author)
-
Clinical measurement of cellular DNA damage hypersensitivity in patients with DNA repair defects
- 2022
-
In: Orphanet Journal of Rare Diseases. - : Springer Science and Business Media LLC. - 1750-1172. ; 17:1
-
Journal article (peer-reviewed)abstract
- Background: DNA repair deficiency disorders are rare inherited diseases arising from pathogenic (disease-causing) variants in genes involved in DNA repair. There are no standardized diagnostic assays for the investigation of pathological significance of unknown variants in DNA repair genes. We hypothesized that our assays for measuring in vitro patient blood cell hypersensitivity to DNA-damaging agents can be used to establish the pathological significance of unknown variants in DNA repair genes. Six patients with variants in the DNA repair genes PRKDC (two siblings), DCLRE1C (two siblings), NBN, and MSH6 were included. Here, we used the cell division assay (CDA) and the gamma-H2AX assay, which were both developed and clinically validated by us, to measure patient cell hypersensitivity in response to ionizing radiation, mitomycin C, cytarabine and doxorubicin. Results: Radiation hypersensitivity was detected in the two patients with variants in the PRKDC gene (p < 0.0001 for both at 3.5 Gy), and the two patients with DCLRE1C variants (p < 0.0001 at 3.5 Gy for sibling 1 and p < 0.0001 at 1 Gy for sibling 2). The cells from the patients with the PRKDC variant were also deficient in removing gamma-H2AX (p < 0.001). The cells from the patient with variants in the NBN gene were hypersensitive to mitomycin C (p = 0.0008) and deficient in both induction and removal of gamma-H2AX in response to radiation. Conclusions: The combination of the CDA and the gamma-H2AX assay is useful in investigating the significance of unknown variants in some DNA repair genes.
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| 35. |
- Hammarsten, Ola, et al.
(author)
-
Evaluation of a Sensitive Copeptin Assay for Clinical Measurement
- 2012
-
In: The Open Clinical Chemistry Journal. - : Bentham Science Publishers Ltd.. - 2588-7785 .- 1874-2416. ; 5:1, s. 21-26
-
Journal article (peer-reviewed)abstract
- Abstract: Background: Copeptin, a marker of vasopressin production, has been introduced for earlier diagnosis of acute myocardial infarction and other clinical emergencies. We evaluated the analytical performance of a new generation copeptin assay in an inter-laboratory trial. Methods: Precision, linearity range, carry-over contamination, the limit of blank and an inter-laboratory comparison trial for the copeptin US KRYPTOR assay were performed on the B·R·A·H·M·S KRYPTOR compact PLUS. Results: The intra-assay imprecision (CVs) was 12.6–2.2% and total imprecision over five days was 12.3-4.3% between 3.1 and 18.2 pmol/L. The assay had excellent linearity between 7-222 pmol/L. The limit of blank was 2.5 pmol/L and the limit of detection was 3.2 pmol/L, but was dependent on the analyte-free material used. No significant difference between sample type, such as serum or different types of plasma or reagent lots, was noted. The copeptin results remained unchanged upon five repeated freeze-thaw cycles. A set of patient samples with a mean copeptin concentration of 2.1-61 pmol/L run at two separate sites showed close correlation (r2=0.99, slope=1.01, intercept=0.35), indicating comparable results across laboratories. Conclusion: The new ultrasensitive copeptin KRYPTOR assay shows excellent inter-lab precision, opening up the possibility for international guidelines to exclude acute myocardial infarction.
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| 36. |
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| 37. |
- Hammarsten, Ola, et al.
(author)
-
Long-time quality assessment of the Elecsys Troponin T hs assay
- 2013
-
In: Clinical Biochemistry. - : Elsevier BV. - 0009-9120. ; 46:12, s. 1055-1057
-
Journal article (peer-reviewed)abstract
- Recently, Roche announced a problem with the calibrators for their high sensitive cardiac troponin T (hscTnT) assay. We have monitored the performance of the assay since its introduction into clinical use in December 2009 and we're in a unique position to provide quantitative information concerning the effects of this problem. Our data document that the measured cTnT concentration in the hscTnT assay dropped by 5.8 ng/L around the 99th percentile before its recalibration in May 2012. Thus, the hscTnT levels in our hospital have been underestimated around this cut-off value since its introduction. The approach we used may be one that other laboratories should consider.
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| 38. |
- Hammarsten, Ola, et al.
(author)
-
Methods for analyzing positive cardiac troponin assay interference
- 2023
-
In: Clinical Biochemistry. - : Elsevier BV. - 0009-9120. ; 116, s. 24-30
-
Journal article (peer-reviewed)abstract
- Objectives: The cardiac damage biomarkers cardiac troponin T (cTnT) and troponin I (cTnI) are used to identify patients with myocardial infarction (MI). To make the correct clinical decisions it is important to identify false positive results due to troponin assay interference. Often interferences are caused by high-molecular weight immunocomplexes called macrotroponin that may result in false troponin elevations because of delayed troponin clearance, or heterophilic antibodies that crosslink troponin assay antibodies and generate troponin-independent signals.Design & Methods: We describe and compare four methods for cTnI assay interference analysis using a protein G spin column method, gel filtration chromatography and two versions of a sucrose gradient ultracentrifugation for cTnI assay interference analysis on five patients with confirmed cTnI interference and one MI patient without cTnI interference from our troponin interference referral center. Results: The protein G spin column method had a high between run variability but was still able to identify all five patients with cTnI interference. The sucrose gradient ultracentrifugation methods and the gel filtration method had simlar performancec and correctly identified the immunocomplexes that caused the cTnI interference. Conclusions: Our experience is that these methods are sufficient to safely confirm or exclude positive cTnI assay interference.
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| 39. |
- Hammarsten, Ola, et al.
(author)
-
Possible mechanisms behind cardiac troponin elevations
- 2018
-
In: Biomarkers. - : Informa UK Limited. - 1354-750X .- 1366-5804. ; 23:8, s. 725-734
-
Journal article (peer-reviewed)abstract
- Cardiac-specific troponins are elevated in blood following cardiac injury and are the preferred diagnostic biomarkers when acute myocardial infarction is suspected clinically. Cardiac troponin (cTn) elevations are also observed in clinical conditions without obvious connection to cardiac injury. Irrespective of the underlying condition, cTn elevation is linked to a poor prognosis, even if the elevation is stable over time. Here, we explore mechanisms that may lead to cTn elevations, including necrosis, apoptosis, necroptosis, cell wounds and decreased clearance. The aim is to broaden the perspective of how we interpret unexpected cTn elevations in patients. The cTn elevations may not be able to serve as direct proof of myocardial necrosis especially in the absence of a clear-cut reason for its release.
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| 40. |
- Hammarsten, Ola, et al.
(author)
-
Possible mechanisms behind cardiac troponin elevations
- 2018
-
In: Biomarkers. - 1354-750X .- 1366-5804. ; 23:8, s. 725-734
-
Research review (peer-reviewed)abstract
- Cardiac-specific troponins are elevated in blood following cardiac injury and are the preferred diagnostic biomarkers when acute myocardial infarction is suspected clinically. Cardiac troponin (cTn) elevations are also observed in clinical conditions without obvious connection to cardiac injury. Irrespective of the underlying condition, cTn elevation is linked to a poor prognosis, even if the elevation is stable over time. Here, we explore mechanisms that may lead to cTn elevations, including necrosis, apoptosis, necroptosis, cell wounds and decreased clearance. The aim is to broaden the perspective of how we interpret unexpected cTn elevations in patients. The cTn elevations may not be able to serve as direct proof of myocardial necrosis especially in the absence of a clear-cut reason for its release.Abbreviations: AMI: acute myocardial infarction; cTn: cardiac troponin; cTnI: cardiac troponin I; cTnT: cardiac troponin T; MLKL: mixed lineage kinase domain-like; TUNEL: terminal deoxynucleotidyl transferase nick end labeling.
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| 41. |
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| 42. |
- Hammarsten, Ola, et al.
(author)
-
Risk of myocardial infarction at specific troponin T levels using the parameter predictive value among lookalikes (PAL)
- 2017
-
In: Clinical Biochemistry. - : PERGAMON-ELSEVIER SCIENCE LTD. - 0009-9120 .- 1873-2933. ; 50:1-2
-
Journal article (peer-reviewed)abstract
- Background: Myocardial infarction is more likely if the heart damage biomarker cardiac troponin T (cTnT) is elevated in a blood sample, indicating that cardiac damage has occurred. No method allows the clinician to estimate the risk of myocardial infarction at a specific cTnT level in a given patient. Methods: Predictive value among lookalikes (PAL) uses pre-test prevalence, sensitivity and specificity at adjacent cTnT limits based on percentiles. PAL is the pre-test prevalence-adjusted probability of disease between two adjacent cTnT limits. If a chest pain patients cTnT level is between these limits, the risk of myocardial infarction can be estimated. Results: The PAL based on percentiles had an acceptable sampling error when using 100 bootstrapped data of 18 different biomarkers from 38,945 authentic lab measurements. A PAL analysis of an emergency room cohort (n = 11,020) revealed that the diagnostic precision of a high-sensitive cTnT assay was similar among chest pain patients at different ages. The higher incidence of false positive results due to non-specific increases in cTnT in the high-age group was counterbalanced by a higher pre-test prevalence of myocardial infarction among older patients, a finding that was missed when using a conventional ROC plot analysis. Conclusions: The PAL was able to calculate the risk of myocardial infarction at specific cTnT levels and could complement decision limits. 2016 The Authors. The Canadian Society of Clinical Chemists. Published by Elsevier Inc.
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| 43. |
- Hammarsten, Ola, et al.
(author)
-
The ratio of cardiac troponin T to troponin I may indicate non-necrotic troponin release among COVID-19 patients
- 2022
-
In: Clinica Chimica Acta. - : Elsevier. - 0009-8981 .- 1873-3492. ; 527, s. 33-37
-
Journal article (peer-reviewed)abstract
- Background: Although cardiac troponin T (cTnT) and troponin I(cTnI) are expressed to similar amount in cardiac tissue, cTnI often reach ten-times higher peak levels compared to cTnT in patients with myocardial necrosis such as in acute myocardial infarction (MI). In contrast, similar levels of cTnT and cTnI are observed in other situations such as stable atrial fibrillation and after strenuous exercise.Objective: Examine cTnT and cTnI levels in relation to COVID-19 disease and MI. Methods: Clinical and laboratory data from the local hospital from an observational cohort study of 27 patients admitted with COVID-19 and 15 patients with myocardial infarction (MI) that were analyzed with paired cTnT and cTnI measurement during hospital care.Results: Levels of cTnI were lower than cTnT in COVID-19 patients (TnI/TnT ratio 0.3, IQR: 0.1-0.6). In contrast, levels of cTnI were 11 times higher compared to cTnT in 15 patients with MI (TnI/TnT ratio 11, IQR: 7-14). The peak cTnI/cTnT ratio among the patients with MI following successful percutaneous intervention were 14 (TnI/ TnT ratio 14, IQR: 12-23). The 5 COVID-19 patient samples collected under possible necrotic events had a cTnI/ cTnT ratio of 5,5 (IQR: 1,9-8,3).Conclusions: In patients with COVID-19, cTnT is often elevated to higher levels than cTnI in sharp contrast to patients with MI, indicating that the release of cardiac troponin has a different cause in COVID-19 patients.
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| 44. |
- Hammarsten, Ola, et al.
(author)
-
Tolkning av analysresultat
- 2018. - 10
-
In: Laurells Klinisk kemi i praktisk medicin. - Lund : Studentlitteratur AB. - 9789144119748 ; , s. 31-53
-
Book chapter (peer-reviewed)
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| 45. |
- Hammarsten, Ola, et al.
(author)
-
Troponin T percentiles from a random population sample, emergency room patients and patients with myocardial infarction
- 2012
-
In: Clinical Chemistry. - : Oxford University Press (OUP). - 1530-8561 .- 0009-9147. ; 58:3, s. 628-637
-
Journal article (peer-reviewed)abstract
- BACKGROUND: High-sensitivity cardiac troponin T (cTnT) assays detect small clinically important myocardial infarctions (MI) but also yield higher rates of false-positive results owing to increased concentrations sometimes present in patients without MI. Better understanding is needed of factors influencing the 99th percentile of cTnT concentrations across populations and the frequency of changes in cTnT concentrations >20% often used in combination with increased cTnT concentrations for diagnosis of MI. METHODS: cTnT percentiles were determined by use of the Elecsys® hscTnT immunoassay (Modular® Analytics E170) in a random population sample, in emergency room (ER) patients, and in patients with non–ST-elevation MI (NSTEMI). Changes in cTnT concentrations were determined in hospitalized patients without MI. RESULTS: The 99th cTnT percentile in a random population sample (median age, 65 years) was 24 ng/L. In ER patients <65 years old without obvious conditions that increase cTnT, the 99th cTnT percentile was 12 ng/L with little age dependence, whereas in those >65 years old it was 82 ng/L and highly age dependent. In hospitalized patients without MI the 97.5th percentile for change in the cTnT concentration was 51%–67%. cTnT remained below the 99th percentile (12 ng/L) in 1% of patients with NSTEMI until 8.5 h after symptom onset and 6 h after ER arrival. CONCLUSIONS: Age >65 years was the dominant factor associated with increased cTnT in ER patients. This age association was more prominent in ER patients than in a random population sample. Changes in serial cTnT concentrations >20% were common in hospitalized patients without MI.
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| 46. |
- Hammarsten, Ola, et al.
(author)
-
Troponinnivåer ger nu bättre hjälp vid misstänkt hjärtinfarkt - Låga nivåer kan med hög säkerhet utesluta hjärtinfarkt : nya analysmetoder ökar den medicinska säkerheten
- 2017
-
In: Läkartidningen. - 0023-7205 .- 1652-7518. ; 114
-
Journal article (peer-reviewed)abstract
- Assessment of troponin levels on the emergency ward Patients with myocardial infarction are at a high risk of sudden death and new cardiovascular events. For this reason, it is important to identify these patients and device treatment to reduce the risk. Patients who seek care with symptoms indicative of myocardial infarction, mainly chest pain, constitute a large proportion of patients at our emergency departments. However, only 5-10 % of these patients have myocardial infarction, whereas the majority has benign causes of their symptoms. This means that it is important not only to identify patients with myocardial infarction quickly, but also to rule out myocardial infarction and other serious disease as fast and safely as possible. With the aid of assays capable of measuring low levels of the cardiac damage biomarker troponin, so-called high-sensitive troponin assays, and several large high-quality clinical studies, myocardial infarction can now be ruled out safely and quickly. If the patient presents with a troponin T level below 5 ng/L and has a normal ECG, myocardial infarction can normally be ruled out without the need for further investigation. In this way, about 30 % of all patients who present with a suspected myocardial infarction can leave the emergency room quickly with a high degree of medical security. On the other hand, when patients present with troponin T levels above 40 ng/L, the patient should normally be admitted to the hospital. These patients are a high-risk group and constitute only 6 % of those who seek medical attention with a suspected myocardial infarction.
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| 47. |
- Hammarsten, Ola, et al.
(author)
-
Use of the cell division assay to diagnose Fanconi anemia patients' hypersensitivity to mitomycin C
- 2021
-
In: Cytometry Part B-Clinical Cytometry. - : Wiley. - 1552-4949 .- 1552-4957. ; 100:3, s. 1894-1906
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Journal article (peer-reviewed)abstract
- The recently reported cell division assay (CDA) was optimized to measure the relative sensitivity of cells to cytotoxic drugs in vitro. Here, we investigated the in vitro hypersensitivity of lymphocytes from Fanconi anemia (FA) patients, to cytotoxic drugs using CDA. Peripheral blood mononuclear cells (PBMC) as well as cell lines derived from FA patients were treated with two DNA interstrand crosslinking (ICL) agents, mitomycin C and cyclophosphamide. Our data indicate that the CDA detects hypersensitivity of cells from FA patients to mitomycin C. Further, cell lines derived from FA-patients were also hypersensitive to mitomycin C as well as cyclophosphamide, when assayed by the CDA. This study suggests that the CDA is a useful alternative for the diagnosis of FA patients' hypersensitivity to ICL agents.
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| 48. |
- Heuts, Samuel, et al.
(author)
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Cardiac troponin release following coronary artery bypass grafting: mechanisms and clinical implications.
- 2023
-
In: European heart journal. - : Oxford University Press (OUP). - 1522-9645 .- 0195-668X. ; 44:2, s. 100-112
-
Journal article (peer-reviewed)abstract
- The use of biomarkers is undisputed in the diagnosis of primary myocardial infarction (MI), but their value for identifying MI is less well studied in the postoperative phase following coronary artery bypass grafting (CABG). To identify patients with periprocedural MI (PMI), several conflicting definitions of PMI have been proposed, relying either on cardiac troponin (cTn) or the MB isoenzyme of creatine kinase, with or without supporting evidence of ischaemia. However, CABG inherently induces the release of cardiac biomarkers, as reflected by significant cTn concentrations in patients with uncomplicated postoperative courses. Still, the underlying (patho)physiological release mechanisms of cTn are incompletely understood, complicating adequate interpretation of postoperative increases in cTn concentrations. Therefore, the aim of the current review is to present these potential underlying mechanisms of cTn release in general, and following CABG in particular (Graphical Abstract). Based on these mechanisms, dissimilarities in the release of cTnI and cTnT are discussed, with potentially important implications for clinical practice. Consequently, currently proposed cTn biomarker cut-offs by the prevailing definitions of PMI might warrant re-assessment, with differentiation in cut-offs for the separate available assays and surgical strategies. To resolve these issues, future prospective studies are warranted to determine the prognostic influence of biomarker release in general and PMI in particular.
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| 49. |
- Hijazi, Ziad
(author)
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New Risk Markers in Atrial Fibrillation
- 2013
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Doctoral thesis (other academic/artistic)abstract
- Atrial fibrillation (AF) confers an independent increased risk of stroke and death. The stroke risk is very heterogeneous and current risk stratification models based on clinical variables, such as the CHADS2 and CHA2DS2VASc score, only offer a modest discriminating value.The aims of this thesis were to study cardiac biomarkers, cardiac troponin and natriuretic peptides e.g. N-terminal prohormone-B-type natriuretic peptide (NT-proBNP), and describe levels in AF patients, investigate the association with stroke or systemic embolism, cardiovascular event, major bleeding and mortality, and to assess how levels of cardiac biomarkers change over time. Cardiac troponin was analyzed with contemporary assays and high sensitivity assays. The study populations consisted of patients with atrial fibrillation and one risk factor for stroke included in the RE-LY (n=6189) and the ARISTOTLE (n=14892) biomarker substudies. Median follow-up time was 2.2 years and 1.9 years, respectively. In a subset of participants (n=2514) data from repeated measurements was available at three months.Cardiac troponin was detectable in 57.0% with the contemporary assay and 99.4% with the high sensitivity assay. NT-proBNP was elevated in approximately three quarters of the participants. In Cox models adjusted for established risk factors the cardiac biomarkers levels was independently associated with stroke or systemic embolism, cardiovascular events, and mortality. Only cardiac troponin was associated with major bleeding. In ROC analyses the prediction of stroke or systemic embolism, cardiovascular events, and mortality increased significantly by addition of cardiac troponin or NT-proBNP to the models. Persistent detectable cardiac troponin (contemporary assay) and elevated NT-proBNP levels were found in a large number of participants. Persistent detectable or elevated levels conferred significantly higher risk for stroke or systemic embolism, cardiovascular events, and mortality. By using both cardiac biomarkers simultaneously the risk stratification improved even further for all outcomes.In conclusion the analyses for the first time display that elevation of troponin I and NT-proBNP are common in patients with AF and independently related to increased risks of stroke, cardiovascular events and mortality. Persistent elevation of troponin and NT-proBNP indicate a worse prognosis than transient elevations or no elevations of either marker. The cardiac biomarkers added substantial improvements to existing risk stratification models.
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- Holmström, Alexandra, et al.
(author)
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An integrated multiple marker modality is superior to NT-proBNP alone in prognostic prediction in all-cause mortality in a prospective cohort of elderly heart failure patients
- 2013
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In: European Geriatric Medicine. - : Elsevier BV. - 1878-7649. ; 4:6, s. 365-371
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Journal article (peer-reviewed)abstract
- Background: Identifying the individual mortality risk for elderly heart failure (HF) patients is challenging because of heterogeneity, comorbidity and higher age. To overcome this, an integrated multiple marker modality has been proposed for better prognostic prediction than a single variable, this has not been evaluated. Aim: The aim of this study is to identify whether a multiple marker modality is better than N-terminal pro-B-type natriuretic peptide (NT-proBNP) alone for all-cause mortality in elderly HF patients. Methods: A prospective cohort of 361 patients (65 +/- 15 years) referred for echocardiography because of suspected HF was studied, among them, 179 had HF (71 +/- 13). In this cohort blood sampling, electrocardiogram and clinical examinations were performed within approximately 24 hours after the echocardiography. To assess prognostic value of multiple marker modality for all-cause mortality, patients were followed up for 24 +/- 7 months. Results: In the three multivariate analyses, NT-proBNP, cystatin C, red blood cell distribution width (RDW), midregional pro-atrial natriuretic peptide (MR-proANP), pulmonary artery pressure, estimated glomerular filtration rate (eGFR) less than 60 mL/min, anemia, diuretics and sinus rhythm are prognostic predictors of all-cause mortality in elderly HF patients. When analyzing all these variables in one multivariate analysis, only NT-proBNP, eGFR less than 60 mL/min, anemia and diuretics are prognostic predictors of all-cause mortality in elderly HF patients. Two different multiple marker models incorporating NT-proBNP, clinical and laboratory variables were created. The sensitivity and specificity of the two different multiple marker modalities are higher than for NT-proBNP alone. The risk score based on multivariate analysis Wald X-2 values is preferred considering its simplicity and feasibility in daily clinical practice. Conclusion: A multiple marker modality was proven to improve prognostic prediction in elderly HF patients compared to NT-proBNP alone. (C) 2013 Elsevier Masson SAS and European Union Geriatric Medicine Society. All rights reserved.
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