16 research outputs found
A Qualitative Study of the Values, Needs, and Preferences of Patients Regarding Stroke Care:The ValueCare Study
Biliverdin Reductase B Is a Plasma Biomarker for Intraplaque Hemorrhage and a Predictor of Ischemic Stroke in Patients with Symptomatic Carotid Atherosclerosis
Background: Intraplaque hemorrhage (IPH) is a hallmark of atherosclerotic plaque instability. Biliverdin reductase B (BLVRB) is enriched in plasma and plaques from patients with symptomatic carotid atherosclerosis and functionally associated with IPH. Objective: We explored the biomarker potential of plasma BLVRB through (1) its correlation with IPH in carotid plaques assessed by magnetic resonance imaging (MRI), and with recurrent ischemic stroke, and (2) its use for monitoring pharmacotherapy targeting IPH in a preclinical setting. Methods: Plasma BLVRB levels were measured in patients with symptomatic carotid atherosclerosis from the PARISK study (n = 177, 5 year follow-up) with and without IPH as indicated by MRI. Plasma BLVRB levels were also measured in a mouse vein graft model of IPH at baseline and following antiangiogenic therapy targeting vascular endothelial growth factor receptor 2 (VEGFR-2). Results: Plasma BLVRB levels were significantly higher in patients with IPH (737.32 ± 693.21 vs. 520.94 ± 499.43 mean fluorescent intensity (MFI), p = 0.033), but had no association with baseline clinical and biological parameters. Plasma BLVRB levels were also significantly higher in patients who developed recurrent ischemic stroke (1099.34 ± 928.49 vs. 582.07 ± 545.34 MFI, HR = 1.600, CI [1.092–2.344]; p = 0.016). Plasma BLVRB levels were significantly reduced following prevention of IPH by anti-VEGFR-2 therapy in mouse vein grafts (1189 ± 258.73 vs. 1752 ± 366.84 MFI; p = 0.004). Conclusions: Plasma BLVRB was associated with IPH and increased risk of recurrent ischemic stroke in patients with symptomatic low- to moderate-grade carotid stenosis, indicating the capacity to monitor the efficacy of IPH-preventive pharmacotherapy in an animal model. Together, these results suggest the utility of plasma BLVRB as a biomarker for atherosclerotic plaque instability
Impact of the lockdown on acute stroke treatments during the first surge of the COVID-19 outbreak in the Netherlands
INTRODUCTION: We investigated the impact of the Corona Virus Disease 2019 (COVID-19) pandemic and the resulting lockdown on reperfusion treatments and door-to-treatment times during the first surge in Dutch comprehensive stroke centers. Furthermore, we studied the association between COVID-19-status and treatment times. METHODS: We included all patients receiving reperfusion treatment in 17 Dutch stroke centers from May 11th, 2017, until May 11th, 2020. We collected baseline characteristics, National Institutes of Health Stroke Scale (NIHSS) at admission, onset-to-door time (ODT), door-to-needle time (DNT), door-to-groin time (DGT) and COVID-19-status at admission. Parameters during the lockdown (March 15th, 2020 until May 11th, 2020) were compared with those in the same period in 2019, and between groups stratified by COVID-19-status. We used nationwide data and extrapolated our findings to the increasing trend of EVT numbers since May 2017. RESULTS: A decline of 14% was seen in reperfusion treatments during lockdown, with a decline in both IVT and EVT delivery. DGT increased by 12 min (50 to 62 min, p-value of < 0.001). Furthermore, median NIHSS-scores were higher in COVID-19 - suspected or positive patients (7 to 11, p-value of 0.004), door-to-treatment times did not differ significantly when stratified for COVID-19-status. CONCLUSIONS: During the first surge of the COVID-19 pandemic, a decline in acute reperfusion treatments and a delay in DGT was seen, which indicates a target for attention. It also appeared that COVID-19-positive or -suspected patients had more severe neurologic symptoms, whereas their EVT-workflow was not affected. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12883-021-02539-4
Genetic variants for head size share genes and pathways with cancer
The size of the human head is highly heritable, but genetic drivers of its variation within the general population remain unmapped. We perform a genome-wide association study on head size (N = 80,890) and identify 67 genetic loci, of which 50 are novel. Neuroimaging studies show that 17 variants affect specific brain areas, but most have widespread effects. Gene set enrichment is observed for various cancers and the p53, Wnt, and ErbB signaling pathways. Genes harboring lead variants are enriched for macrocephaly syndrome genes (37-fold) and high-fidelity cancer genes (9-fold), which is not seen for human height variants. Head size variants are also near genes preferentially expressed in intermediate progenitor cells, neural cells linked to evolutionary brain expansion. Our results indicate that genes regulating early brain and cranial growth incline to neoplasia later in life, irrespective of height. This warrants investigation of clinical implications of the link between head size and cancer.</p
Circulatory markers of immunity and carotid atherosclerotic plaque
Background and aims : We aimed to determine the association of circulatory markers of innate and adaptive immunity with carotid atherosclerotic plaque characteristics. Methods : In 1602 participants from the population-based Rotterdam Study with subclinicalcarotid atherosclerosis, blood sampling was performed to determine granulocyte, platelet, monocyte (innate immunity) and lymphocyte (adaptive immunity) counts, from which the granulocyte-to-lymphocyte ratio [GLR], platelet-to-lymphocyte ratio [PLR], monocyte-to-lymphocyte ratio [MLR] and systemic immune-inflammation index [SII] were calculated. All participants underwent carotid MRI for evaluation of plaque characteristics. Plaque size (stenosis >30%, maximum plaque thickness) and plaque composition (presence of intraplaque hemorrhage [IPH], lipid-rich necrotic core [LRNC], and calcification) were assessed. Using linear and logistic regression models, the association of innate and adaptive immunity markers with plaque size and plaque components, adjusting for relevant confounders, was assessed. Results : Higher levels of granulocytes were significantly associated with larger plaque thickness (mean difference [Ln (mm)] per Ln increase granulocyte count [95% CI]: 0.06 [0.02; 0.10]). Conversely, more lymphocytes related with smaller maximum plaque thickness (mean difference [Ln (mm)] per Ln increase lymphocyte count: 0.09 [-0.14;-0.04]) and a lower prevalence of IPH (odds ratio per Ln increase lymphocyte count: 0.60 [0.37; 0.97]). Moreover, all ratio measures were associated with larger plaque thickness, of which the MLR also associated with more frequent LRNC (odds ratio per Ln increase MLR: 1.26 [1.02; 1.56]). Conclusions : The innate immunity links to larger plaques, whilst the adaptive immunity seems to relate to smaller plaques and a lower frequency of IPH. These results suggest that an imbalance in innate and adaptive immunity may play a role in the vulnerability of carotid atherosclerotic plaques
Advances in multimodality carotid plaque imaging: AJR expert panel narrative review
Contemporary imaging methods provide detailed visualization of carotid atherosclerotic plaque, enabling a major evolution of in vivo carotid plaque imaging evaluation. The degree of luminal stenosis in the carotid artery bifurcation, as assessed by ultrasound, has historically served as the primary imaging feature for determining ischemic stroke risk and the potential need for surgery. However, stroke risk may be more strongly driven by the presence of specific characteristics of vulnerable plaque, as visualized on CT and MRI, than by traditional ultrasound-based assessment of luminal narrowing. This review highlights six promising imaging-based plaque characteristics that harbor unique information regarding plaque vulnerability: maximum plaque thickness and volume, calcification, ulceration, intraplaque hemorrhage, lipid-rich necrotic core, and thin or ruptured fibrous cap. Increasing evidence supports the association of these plaque characteristics with risk of ischemic stroke, although these characteristics have varying suitability for clinical implementation. Key aspects of CT and MRI protocols for carotid plaque imaging are also considered. Practical next steps and hurdles are explored for implementing routine imaging assessment of these plaque characteristics in addition to, or even as replacement for, traditional assessment of the degree of vascular stenosis on ultrasound, in the identification of individuals at high risk of ischemic stroke
Sex Differences in Plaque Composition and Morphology Among Symptomatic Patients With Mild-to-Moderate Carotid Artery Stenosis.
Dolichoarteriopathies of the extracranial internal carotid artery
Background and purpose: Dolichoarteriopathies of the extracranial part of the internal carotid artery (ICA) are associated with cerebrovascular events, yet information on their prevalence and risk factors remains limited. The aim of the present study therefore was to study the prevalence and risk factors of dolichoarteriopathies in a sample of patients with cerebrovascular symptoms from the Plaque At RISK (PARISK) study. Methods: In a random sample of 100 patients from the PARISK study, multidetector computed tomography angiography (MDCTA) was performed as part of clinical workup. On MDCTA, we evaluated the extracranial trajectory of the ICA by measuring the length (in millimeters), the tortuosity index (TI; defined as the ICA length divided by the shortest possible distance from bifurcation to skull base), and dolichoarteriopathy type (tortuosity, coiling or kinking). Next, we investigated the association between cardiovascular risk factors and these measurements using linear and logistic regression analyses. Results: The mean (standard deviation) length of the ICA was 93 (± 14) mm, with a median (interquartile range) TI of 1.2 (1.1–1.3). The overall prevalence of dolichoarteriopathies was 69%, with tortuosity being the most common (72%), followed by coiling (20%), and kinking (8%). We found that age and obesity were associated with a higher TI: difference per 10-year increase in age: 0.05 (95% confidence interval [CI] 0.02–0.08) and 0.16 (95% CI 0.07–0.25) for obesity. Obesity and hypercholesterolemia were associated with a more severe type of dolichoarteriopathy (odds ratio [OR] 2.07 [95% CI 1.04–4.12] and OR 2.17 [95% CI 1.02–4.63], respectively). Conclusion: Dolichoarteriopathies in the extracranial ICA are common in patients with cerebrovascular symptoms, and age, obesity and hypercholesterolemia may play an important role in the pathophysiology of these abnormalities.</p