Temporal changes of biomarkers in myocardial infarction patients with non-obstructive compared to obstructive coronary arteries

Background About 5–10% of all myocardial infarction (MI) patients have non-obstructive coronary arteries (MINOCA). The pathobiology of MINOCA is largely unknown compared to myocardial infarction with obstructive coronaries (MI-CAD). Purpose To investigate whether baseline concentrations and temporal changes of circulating biomarkers may offer insights into the activation of pathophysiological pathways in MINOCA compared to MI-CAD. Methods From the PLATelet inhibition and patient Outcomes (PLATO) trial, we retrospectively identified 114 patients with MINOCA (adjudicated MI, coronary stenoses <50% and excluding patients with previous coronary revascularization) and 2750 patients with MI-CAD (adjucated MI and stenoses ≥50%) with available biomarker data. Concentrations of high sensitivity cardiac troponin T (hs-cTnT), C-reactive protein (CRP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were centrally measured by immunoassays in plasma samples obtained at randomization/baseline (median 15 hours from index event) and after one month. Differences in biomarker concentrations and their changes were evaluated by Wilcoxon-Mann-Whitney tests and data at one month were also analysed with adjusted linear regression models. Results In MINOCA patients, median concentrations decreased during one month from 238 to 9 ng/L for hs-cTnT, from 3.5 to 1.6 mg/L for CRP and from 507 to 228 pmol/L for NT-proBNP (Figure 1 and 2). In MI-CAD patients, median concentrations decreased from 198 to 13 ng/L for hs-cTnT, from 3.2 to 2.3 mg/L for CRP and increased from 372 to 566 pmol/L for NT-proBNP. Compared to MI-CAD, the baseline concentrations were higher in MINOCA for NT-proBNP (p=0.011), but similar for hs-cTnT (p=0.555) and CRP (p=0.834). However, patients with MINOCA had statistically larger reductions of concentrations from baseline to one month for hs-cTnT (p=0.002), CRP (p=0.005) and NT-proBNP (p<0.001) as compared to patients with MI-CAD. At one month, concentrations were lower in MINOCA than MI-CAD patients for all three biomarkers, which remained significant after adjustment for the baseline biomarker concentration, clinical characteristics and medications (p<0.001). Conclusions In MINOCA compared to MI-CAD patients, higher concentrations of NT-proBNP and similar concentrations of hs-cTnT and CRP at baseline indicate a higher degree of acute myocardial dysfunction but similar degree of acute myocardial injury and inflammation. Furthermore, concentrations of these biomarkers were lower at one month in MINOCA, suggesting other or less remaining underlying disease processes after MI in MINOCA than MI-CAD. FUNDunding Acknowledgement Type of funding sources: Other. Main funding source(s): The present study was supported by Swedish Foundation for Strategic Research/Swedish Association of Local Authorities and Regions. The PLATO study and the biomarker analyses were sponsored by AstraZeneca.

Baseline Concentrations of 11 Elements as a Function of Land Uses in Surface Soils of the Katangese Copperbelt Area (D.R. Congo)

The Katangese Copperbelt area (KCA) located south-eastern of D.R. Congo presents high concentration of metal trace elements (MTE) in several soils due to a rich natural geochemical background, and intense mining activities, causing serious health issues to humans and animals. However, the lack of data on specific baseline concentrations makes it difficult to properly assess and monitor the environmental quality of soils in the region. In this study, the baseline concentration of 11 potentially toxic MTE (i.e., Mn, Zn, Cu, Co, Cr, Pb, Cd, Ti, Ni, Al, and Fe) was assessed in topsoils of the KCA, and the possible influence of land uses (croplands, forest and mining areas) was examined. Result delineated clear variability of metal concentrations across land uses. The highest concentrations of Cu and Zn found in mining areas than croplands and forests demonstrated a prevalent influence of mining activities in altering the natural background of metals concentrations in the region. By contrast, croplands and forests shared a similar trend of Al and Mn contents, suggesting a mild influence on agricultural activity. Intriguingly, however, higher Cu and Co contents were found in forests compared to croplands. For all the three studied land uses allocation, no straightforward relation was found between metal concentrations and soil total acidity. This study provides valuable information for legislative purposes and for soil quality reference values.

Metabolomic signatures associated with depression and predictors of antidepressant response in humans: A CAN-BIND-1 report

One of the biggest challenges in treating depression is the heterogeneous and qualitative nature of its clinical presentations. This highlights the need to find quantitative molecular markers to tailor existing treatment strategies to the individual’s biological system. In this study, high-resolution metabolic phenotyping of urine and plasma samples from the CAN-BIND study collected before treatment with two common pharmacological strategies, escitalopram and aripiprazole, was performed. Here we show that a panel of LDL and HDL subfractions were negatively correlated with depression in males. For treatment response, lower baseline concentrations of apolipoprotein A1 and HDL were predictive of escitalopram response in males, while higher baseline concentrations of apolipoprotein A2, HDL and VLDL subfractions were predictive of aripiprazole response in females. These findings support the potential of metabolomics in precision medicine and the possibility of identifying personalized interventions for depression.

Plasma Concentrations of Extracellular Vesicles Are Decreased in Patients with Post-Infarct Cardiac Remodelling

Background, the mechanisms underlying left ventricular remodelling (LVR) after acute myocardial infarction (AMI) remain obscure. In the course of AMI, blood cells and endothelial cells release extracellular vesicles (EVs). We hypothesized that changes in EV concentrations after AMI may underlie LVR. Methods, plasma concentrations of EVs from endothelial cells (CD146+), erythrocytes (CD235a+), leukocytes (CD45+), platelets (CD61+), activated platelets (P-selectin+), and EVs exposing phosphatidylserine after AMI were determined by flow cytometry in 55 patients with the first AMI. LVR was defined as an increase in left ventricular end-diastolic volume by 20% at 6 months after AMI, compared to baseline. Results, baseline concentrations of EVs from endothelial cells, erythrocytes and platelets were lower in patients who developed LVR (p ≤ 0.02 for all). Concentrations of EVs from endothelial cells and erythrocytes were independent LVR predictors (OR 8.2, CI 1.3–54.2 and OR 17.8, CI 2.3–138.6, respectively) in multivariate analysis. Combining the three EV subtypes allowed to predict LVR with 83% sensitivity and 87% specificity. Conclusions, decreased plasma concentrations of EVs from endothelial cells, erythrocytes and platelets predict LVR after AMI. Since EV release EVs contributes to cellular homeostasis by waste removal, decreased concentrations of EVs may indicate dysfunctional cardiac homeostasis after AMI, thus promoting LVR.

Insignificant Impact of the “Stay-At-Home” Order on Ambient Air Quality in the Memphis Metropolitan Area, U.S.A.

The lockdowns due to the COVID-19 pandemic have been reported to reduce ambient air pollution in many cities globally. This study aims to examine whether air pollution dropped in Memphis, a typical U.S. metropolitan city and transportation hub, during the lockdown from 25 March to 4 May, 2020. Daily air pollution data measured at five representative monitoring stations in the Memphis Metropolitan Area were downloaded from the U.S. Environmental Protection Agency’s Air Quality System. The mean concentrations of fine particulate matter (PM2.5), nitrogen dioxide (NO2), and ozone during the lockdown were compared with the baseline concentrations measured during the same periods in 2017–2019 using linear regression models. The average vehicle miles traveled (VMT) reduced by 57% in this region during the lockdown compared to that during 1–24 March, 2020. The mean (± standard deviation) concentrations of PM2.5, NO2, and ozone were 7.5 ± 2.6 μg/m3, 16.5 ± 9.4 ppb, and 44.5 ± 8.4 ppb, respectively, during the lockdown. They did not statistically differ from the baseline concentrations, nor were they lower than the mean concentrations in the prior month (25 February–24 March, 2020), after accounting for meteorological conditions. The lack of effect could be explained by the small contribution of traffic emissions to air pollution. The results suggest that the “stay-at-home” order had an insignificant impact on reducing air pollution in Memphis.

Clinical Significance of Monitoring Circulating Free DNA and Plasma Heat Shock Protein 90alpha in Patients with Esophageal Squamous Cell Carcinoma

Background: Esophageal squamous cell carcinoma (ESCC) is the predominant histological type of esophageal cancer in China and has an extremely poor prognosis. Circulating free DNA (cfDNA) and plasma heat shock protein 90alpha (Hsp90a) are two novel noninvasive biomarkers for diagnosis and prognostic prediction of several types of cancer. However, to the best of our knowledge, the roles of the two biomarkers in ESCC are still unknown.Methods: We recruited 93 primary ESCC patients and detected plasma concentrations of the two markers at different time points, including 1–3 days pre-chemotherapy, 1–7 days pre-surgery and 7–14 days post-surgery. Baseline concentrations of the two markers were associated with main characteristics of ESCC patients which were collected at first diagnosis. Correlation between the two markers and traditional serum biomarkers at baseline was also examined. Furthermore, dynamic changes of the cfDNA and Hsp90α concentrations among different time points and the potential clinical significance were assessed.Results: There was no significant association between baseline concentrations of the two markers and clinical features. Especially, cfDNA demonstrated stronger correlation with other circulating biomarkers than Hsp90α at baseline level. Importantly, both cfDNA and Hsp90α concentrations were significantly increased after surgery. Kaplan-Meier survival analysis showed that a change in concentration of cfDNA (ΔcfDNA) but not Hsp90α (ΔHSP90ɑ) between pre-surgery and post-surgery had significant effect on the overall survival of surgical patients with ESCC. Thus, ΔcfDNA evaluation could be a promising prognostic marker for surgical ESCC patients.Conclusions: Our findings may improve the understanding of the function of cfDNA and Hsp90α in ESCC.

SAT-LB79 Biotin Depleting Procedure Does Not Impact the Reliability of TSH, LH and FSH Immunoassays

Background: Biotin interference has become a major problem with some laboratory immunoassays, leading to erroneous tests results and potentially harmful clinical consequences. There is therefore a clinical need to easily identify the interference and to overcome its effect to avoid harmful consequences for patients. The aim of this study was to demonstrate the VeraPrep BiotinTM procedure, a biotin depleting device, does not impact the immunoreactivity of TSH, LH and FSH immunoassays.Materials and methods: Nine samples (4 from women and 5 from men) were tested with two-sites electrochemiluminescent immunoassays (Cobas e602, Roche diagnostics) for the measurement of three pituitary hormones, TSH, LH and FSH. The samples were first measured without any treatment (baseline) and then retested after treatment with VeraPrep Biotin™ procedure. Percent (%) difference was calculated between post-treatment and baseline to determine if the biotin depleting device impact the immunoassays immunoreactivity.Results: The median baseline concentrations for TSH, LH and FSH were 2.3 mIU/L (standard deviation (SD): 1.5), 4.9 IU/L (19.0) and 5.3 IU/L (17.5), respectively. The median concentrations after treatment with the VeraPrep Biotin™ procedure for TSH, LH and FSH were 2.3 mIU/L (1.5), 4.9 IU/L (18.9) and 4.9 IU/L (16.5), respectively, and were not statistically different from baseline (P = 0.976). The mean recoveries after treatment were 99.5%, 98.6% and 95.4% for TSH, LH and FSH, respectively.Conclusions: The concentrations of the TSH, LH and FSH assays were not impacted by the pretreatment with the VeraPrep Biotin™ procedure, confirming its ability to help clinical laboratories to overcome biotin interference.