Noreen van der Linden

Immature platelet fraction measured on the Sysmex XN hemocytometer predicts thrombopoietic recovery after autologous stem cell transplantation

A period of thrombocytopenia is common after stem cell transplantation (SCT). To prevent serious bleeding complications, prophylactic platelet transfusions are administered. Previous studies have shown that a rise in immature platelets precedes recovery of platelet count. Our aim was to define a cutoff value for immature platelets predicting thrombopoietic recovery within 2 d.

Vitamin D Status Does Not Affect Disability Progression of Patients with Multiple Sclerosis over Three Year Follow-Up.

Background and Objective The risk of developing multiple sclerosis (MS) as well as MS disease activity is associated with vitamin D (25(OH)D) status. The relationship between the main functional disability hallmark of MS, disability progression, and 25(OH)D status is less well established though, especially not in MS patients with progressive disease. Methods This retrospective follow-up study included 554 MS patients with a serum baseline 25(OH)D level and Expanded Disability Status Scale (EDSS) with a minimum follow-up of three years. Logistic regressions were performed to assess the effect of baseline 25(OH)D status on relapse rate. Repeated measures linear regression analyses were performed to assess the effect on disability and disability progression. Results Baseline deseasonalized 25(OH)D status was associated with subsequent relapse risk (yes/no), but only in the younger MS patients (≤ 37.5 years; OR = 0.872, per 10 nmol/L 25(OH)D, p = 0.041). Baseline 25(OH)D status was not significantly associated with either disability or disability progression, irrespective of MS phenotype. Conclusion Within the physiological range, 25(OH)D status is just significantly associated with the occurrence of relapses in younger MS patients, but is not associated with disability or disability progression over three years follow-up. Whether high dose supplementation to supra physiological 25(OH)D levels prevents disability progression in MS should become clear from long term follow-up of supplementation studies.

Origin of Cardiac Troponin T Elevations in Chronic Kidney Disease

Plasma concentrations of cardiac troponins, the preferred biomarkers for the diagnosis of acute myocardial infarction, are often persistently elevated in patients with chronic kidney disease (CKD). The origin of these elevations is unknown: Is it the heart, by increased release, or the kidneys, by decreased renal elimination? In clinical practice, this equivocal view on troponin elevations in patients with reduced glomerular clearance underlies countless clinical discussions among physicians and may delay rapid initiation of adequate treatment when these patients present with chest pain. In the present study, we aimed to discriminate between increased cardiac release and reduced renal elimination as the main process underlying this phenomenon. Specifically, we used the recently demonstrated rhythmic diurnal oscillation pattern of troponin T as a model to assess the contribution of impaired renal elimination to persistently elevated cardiac troponin levels in patients with CKD.1 The diurnal troponin T rhythm is characterized by gradually decreasing concentrations throughout daytime and rising concentrations during nighttime.1 If decreased renal clearance, and not increased production, is the key driver of elevated troponins in patients with CKD, the increased half-life and subsequent accumulation of cardiac troponin T will fade its diurnal rhythm. …

Prognostic value of basal high-sensitive cardiac troponin levels on mortality in the general population: A meta-analysis.

AbstractInterest in the use of cardiac troponin T (cTnT) and cardiac troponin I (cTnI) has expanded from diagnosis of acute myocardial infarction to risk assessment for morbidity and mortality. Although cTnT and cTnI were shown to have equivalent diagnostic performance in the setting of suspected acute myocardial infarction, potential prognostic differences are largely unexplored.The aim of this study is to quantify and compare the relationship between cTnT and cTnI, and cardiovascular and all-cause mortality in the general population.Medline, Embase, and the Cochrane Library (from inception through October 2016) were searched for prospective observational cohort studies reporting on the prognostic value of basal high-sensitive cTnT and/or cTnI levels on cardiovascular and all-cause mortality in the general population. Data on study characteristics, participants’ characteristics, outcome parameters, and quality [according to the Effective Public Health Practice Project (EPHPP) “Quality Assessment Tool For Quantitative Studies] were retrieved. Hazard ratios per standard deviation increase in basal cardiac troponin level (HR per 1-SD; retrieved from the included articles or estimated) were pooled using a random-effects model.On a total of 2585 reviewed citations, 11 studies, with data on 65,019 participants, were included in the meta-analysis. Random effects pooling showed significant associations between basal cardiac troponin levels and HR for cardiovascular and all-cause mortality [HR per 1-SD 1.29 (95% confidence interval, 95% CI, 1.20–1.38) and HR per 1-SD 1.18 (95% CI, 1.11–1.26), respectively]. Stratified analyses showed higher HRs for cTnT than cTnI [cardiovascular mortality: cTnT HR per 1-SD 1.37 (95% CI, 1.23–1.52); and cTnI HR per 1-SD 1.21 (95% CI, 1.16–1.26); all-cause mortality: cTnT HR per 1-SD 1.31 (955 CI, 1.13–1.53); and cTnI HR per 1-SD 1.14 (95% CI, 1.06–1.22)]. These differences were significant (P < 0.01) in meta-regression analyses for cardiovascular mortality but did not reach statistical significance for all-cause mortality.Elevated, basal cTnT, and cTnI show robust associations with an increased risk of cardiovascular and all-cause mortality during follow-up in the general population.Systematic review registration number PROSPERO CRD42014006964.

Within-day biological variation and hour-to-hour reference change values for hematological parameters

Abstract 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.

The effect of exercise training on the course of cardiac troponin T and I levels: three independent training studies.

With the introduction of high-sensitive assays, cardiac troponins became potential biomarkers for risk stratification and prognostic medicine. Observational studies have reported an inverse association between physical activity and basal cardiac troponin levels. However, causality has never been demonstrated. This study investigated whether basal cardiac troponin concentrations are receptive to lifestyle interventions such as exercise training. Basal high-sensitive cardiac troponin T (cTnT ) and I (cTnI) were monitored in two resistance-type exercise training programs (12-week (study 1) and 24-week (study 2)) in older adults (≥65 years). In addition, a retrospective analysis for high sensitive troponin I in a 24-week exercise controlled trial in (pre)frail older adults was performed (study 3). In total, 91 subjects were included in the final data analyses. There were no significant changes in cardiac troponin levels over time in study 1 and 2 (study 1: cTnT −0.13 (−0.33–+0.08) ng/L/12-weeks, cTnI −0.10 (−0.33–+0.12) ng/L/12-weeks; study 2: cTnT −1.99 (−4.79–+0.81) ng/L/24-weeks, cTnI −1.59 (−5.70–+2.51) ng/L/24-weeks). Neither was there a significant interaction between training and the course of cardiac troponin in study 3 (p = 0.27). In conclusion, this study provides no evidence that prolonged resistance-type exercise training can modulate basal cardiac troponin levels.

Twenty-Four-Hour Biological Variation Profiles of Cardiac Troponin I in Individuals with or without Chronic Kidney Disease

To the Editor: The interpretation of cardiac troponin concentrations at presentation and their dynamics over time is a key aspect in the diagnostic workup of acute myocardial infarction in the absence of characteristic electrocardiogram abnormalities. The present biological variation study sought to examine and compare the hour-to-hour biological variation in cardiac troponin I (cTnI) over 24 h in individuals with and without chronic kidney disease (CKD).1 This study was carried out according to the principles of the Declaration of Helsinki and approved by the Institutional Review Board and Ethics Committee of Maastricht University Medical Center (clinicaltrials.gov: NCT02091427 and NCT02210897). All participants provided written informed consent. From 8:30 AM until 9:30 AM the next day, 20 individuals with clinically stable CKD stage 3 or higher (estimated glomerular filtration rate (eGFR) <59 mL · min−1 · 1.73 m−2) and 20 individuals without CKD were restricted to the laboratory environment. All individuals were of Caucasian ethnicity. Every hour during 24 h, …

Combining High-Sensitivity Cardiac Troponin I and Cardiac Troponin T in the Early Diagnosis of Acute Myocardial Infarction

Background: Combining 2 signals of cardiomyocyte injury, cardiac troponin I (cTnI) and T (cTnT), might overcome some individual pathophysiological and analytical limitations and thereby increase diagnostic accuracy for acute myocardial infarction with a single blood draw. We aimed to evaluate the diagnostic performance of combinations of high-sensitivity (hs) cTnI and hs-cTnT for the early diagnosis of acute myocardial infarction. Methods: The diagnostic performance of combining hs-cTnI (Architect, Abbott) and hs-cTnT (Elecsys, Roche) concentrations (sum, product, ratio, and a combination algorithm) obtained at the time of presentation was evaluated in a large multicenter diagnostic study of patients with suspected acute myocardial infarction. The optimal rule-out and rule-in thresholds were externally validated in a second large multicenter diagnostic study. The proportion of patients eligible for early rule-out was compared with the European Society of Cardiology 0/1 and 0/3 hour algorithms. Results: Combining hs-cTnI and hs-cTnT concentrations did not consistently increase overall diagnostic accuracy as compared with the individual isoforms. However, the combination improved the proportion of patients meeting criteria for very early rule-out. With the European Society of Cardiology 2015 guideline recommended algorithms and cut-offs, the proportion meeting rule-out criteria after the baseline blood sampling was limited (6% to 24%) and assay dependent. Application of optimized cut-off values using the sum (9 ng/L) and product (18 ng2/L2) of hs-cTnI and hs-cTnT concentrations led to an increase in the proportion ruled-out after a single blood draw to 34% to 41% in the original (sum: negative predictive value [NPV] 100% [95% confidence interval (CI), 99.5% to 100%]; product: NPV 100% [95% CI, 99.5% to 100%]) and in the validation cohort (sum: NPV 99.6% [95% CI, 99.0–99.9%]; product: NPV 99.4% [95% CI, 98.8–99.8%]). The use of a combination algorithm (hs-cTnI <4 ng/L and hs-cTnT <9 ng/L) showed comparable results for rule-out (40% to 43% ruled out; NPV original cohort 99.9% [95% CI, 99.2–100%]; NPV validation cohort 99.5% [95% CI, 98.9–99.8%]) and rule-in (positive predictive value [PPV] original cohort 74.4% [95% Cl, 69.6–78.8%]; PPV validation cohort 84.0% [95% Cl, 79.7–87.6%]). Conclusions: New strategies combining hs-cTnI and hs-cTnT concentrations may significantly increase the number of patients eligible for very early and safe rule-out, but do not seem helpful for the rule-in of acute myocardial infarction. Clinical Trial Registration: URL (APACE): https://www.clinicaltrial.gov. Unique identifier: NCT00470587. URL (ADAPT): www.anzctr.org.au. Unique identifier: ACTRN12611001069943.

Large Variation in Measured Cardiac Troponin T Concentrations after Standard Addition in Serum or Plasma of Different Individuals

To the Editor: During acute myocardial infarction (AMI), 1 cardiac troponin T (cTnT) is released from the damaged myocardium. One would expect a strong correlation between concentrations of cTnT measured in the blood after AMI and the extent of myocardial damage. However, various studies have shown a rather moderate correlation between infarct size and cTnT concentrations (1, 2). Frequently considered explanations for this phenomenon are methodological or focused on physiological factors associated with differences in release and elimination of cTnT (2). In contrast, less attention has been paid to the possible presence of inherent factors in the blood, such as (auto)antibodies or proteases, that might modify cTnT or interfere with the assay. We hypothesized that these factors may be ubiquitously present in the general population and might affect the measured concentrations of cTnT in individuals. We measured cTnT, cTnI, creatine kinase MB isoenzyme (CK-MB), and myoglobin concentrations in sera from 24 healthy volunteers (age range 22–54 years) before and after the addition of serum from a patient suffering from AMI (age 59 years, cTnT concentration approximately 19.5 μg/L). All participants gave written informed consent and leftover material was used in accordance with the code of proper secondary use of human tissue …

Clinical and echocardiographic determinants in bicuspid aortic dilatation Results from a longitudinal observational study

AbstractBicuspid aortic valve (BAV) disease is associated with aortic dilatation. Timing of follow-up and surgery is challenging. Hence, there is an unmet clinical need for additional risk stratification. It is unclear whether valve morphology is associated with dilatation rates. Therefore, the objective of this study was to examine the association between clinical and echocardiographic determinants (including valve morphology) and aortic dimension and the progression rate of dilatation.Aortic dimensions were assessed on serial echocardiographic images between 1999 and 2014 in a population of 392 patients with BAVs in a tertiary care center in the Netherlands. Analyses using mixed linear models were performed.Mean age of participants was 48 ± 17 years and 69% were male. BAV morphology was associated with aortic dimensions, as well as age, sex, BSA, and valvular dysfunction. Tubular ascending aorta, sinus of Valsalva, and sinotubular junction showed a dilatation rate of 0.32, 0.18, and 0.06 mm/year, respectively. Dilatation rate was not associated with valve morphology.In the present study, there is no association between BAV morphology and aortic dilatation rates. Therefore, morphology is of limited use in prediction of aortic growth. Discovering fast progressors remains challenging.