Vascular Profile Research Articles

Retinal neurovascular assessment and choroidal vascularity index in patients with keratoconus

This study aims to evaluate the macular and the optic nerve head thickness and vascular profiles in KC patients and compare them with two groups of healthy emmetrope and subjects with myopic-astigmatism. This cross-sectional study was conducted at Khatam-Al-Anbia Eye Hospital between 2022 and 2023. Subjects aged 18 to 40 were prone to be included in the study. The participants in this study were grouped into three categories: emmetrope (E), myopic-astigmatic (MA), and keratoconus (KC). All participants underwent a comprehensive ocular examination, as well as macular and optic nerve head (ONH) optical coherence tomography angiography (OCTA). In this study, 143 subjects, 50 cases in the KCN group, 46 cases in the E group, and 47 cases in the MA group, enrolled. There was no difference between the three groups regarding age (p = 0.123) and gender (p = 0.632). The superficial and deep capillary densities at the fovea, parafovea, and perifovea were significantly lower in KC patients than in the control groups (p < 0.01). The radial peripapillary capillary (RPC)- all vessels’ density is significantly lower in the KC group (p < 0.001). Besides, the choroidal vascularity index (CVI) and choroidal luminal area (CLA) were considerably higher in KC patients (p < 0.001). The macular and ONH vascular profile in KC patients significantly differs from the vascular profile of healthy controls. Further scientific evidence regarding the systemic implications of keratoconus on the vascular system would be desirable to understand the connections between KC and vascular disease.

Coadministration of PEGylated apohemoglobin and haptoglobin can limit vascular dysfunction in the microcirculation and prevent acute inflammation.

Unfortunately, during pathological conditions resulting in chronic hemolysis cell-free hemoglobin (Hb) is released into the circulation that releases free heme, resulting in several complications. One approach to prevent these toxicities is the administration of supplemental scavenger proteins, haptoglobin (Hp) and hemopexin (Hpx). The goal of this body of work is to objectively measure the levels of vascular reactivity and inflammatory profiles after an infusion of acellular hemoglobin in animals that were given a coadministration of PEGylated human apohemoglobin (PEG-apoHb), a hemopexin (Hpx)-mimetic that can scavenge free heme from hemoglobin, together with human plasma-derived Hp that can scavenge dimerized Hb. Using intravital microscopy, Golden Syrian hamsters instrumented with a dorsal window chamber were used to evaluate the in vivo effects of four experimental groups that were then challenged with a hypovolemic injection (10% of the animal's blood volume) of human Hb (hHb, 5 g/dL). The four experimental groups consisted of: 1) lactated Ringer's solution (control), 2) PEG-apoHb only, 3) Hp only, and 4) PEG-apoHb + Hp. The microvascular hemodynamics (diameter and flow) in arterioles and venules were recorded at baseline, 20 min after treatment, and 20 min after hHb challenge. Systemic parameters (blood pressure and heart rate), blood gases (pH, Pco2, and Po2), blood parameters (Hb concentration and hematocrit), and multiorgan functionality/inflammation were also measured. Our results suggest that coadministration of PEG-apoHb + Hp as a booster before the infusion of acellular hemoglobin significantly prevented vasoconstriction in the microcirculation, significantly increased the number of functional capillaries, and significantly reduced inflammation.NEW & NOTEWORTHY Coadministration of PEGylated human apohemoglobin (PEG-apoHb)-a hemopexin (Hpx) mimetic that can scavenge free heme-and human plasma-derived haptoglobin (Hp) that can scavenge hemoglobin (Hb), reduces microcirculatory dysfunction and cardiac and kidney inflammation in a Hb-challenge model.

EP191 - Laparoscopic right hemicolectomy in a patient with malrotation of bowel and ascending colon tumour

Abstract Aims Ascending colon (AC) tumour in a patient with malrotation of bowel can present diagnostic and surgical challenges. We present such a case managed by laparoscopic resection, and share the difficulties encountered and our preparation to achieve a good outcome Methods A 72-year-old female with iron deficiency anaemia underwent CT colonography after an incomplete optical colonoscopy. The scan revealed malrotation, a pelvic caecum and a midline ascending colon, and a lesion suspicious of cancer in ascending colon with a CT staging of T3N0M0. Patient was scheduled for elective laparoscopic right hemicolectomy. Results Review of vascular anatomy was carried out with radiologist. Several modifications to standard procedure was used – first port-entry site, number of ports, plan of dissection, and site of specimen extraction. Additional challenges were due to the high BMI (40 kg/m2). Patient was discharged on day-7 without major complications. Conclusion Multidisciplinary discussion, optimal pre-operative preparation, and thorough understanding of the vascular profile leads to successful management of these rare presentations by minimally invasive surgery. Pre-operative CT-scan is essential before planning surgical management. Laparoscopic right-hemicolectomy although challenging, can be successfully performed with appropriate expertise.

Abstract Tu031: Immunosuppression Drug Modulation of Endothelial Cell Function

Heart transplantation is a life-saving therapy for patients with end-stage heart failure with over 4,000 transplants occurring per year. The use of immunosuppression drugs is necessary in post transplantation to prevent graft rejection. Proliferation signal inhibitors have previously been shown to effectively reduce the incidence of cardiac allograft vasculopathy (CAV) compared to calcineurin inhibitors but the differential mechanisms that drive this benefit and differences in vascular profile of immunosuppression drugs remain incompletely understood. In this study, we examined the direct effect of immunosuppressive agents on endothelial function to define cellular mechanisms that may contribute to differential vascular phenotypes. We used endothelial cells derived from human induced pluripotent stem cells (iPSCs) and treated them with calcineurin inhibitor (tacrolimus), mTOR inhibitor (sirolimus), or vehicle for 5 days with daily media changes. We examined endothelial function using scratch wound assay, tube formation assay, and LDL uptake. We also examined metabolic changes using Seahorse assay owing to metabolic changes induced by immunosuppression drugs in other organs. Our results indicate mTOR inhibitor (sirolimus) resulted in a reduction in endothelial cell proliferation and migration using the scratch wound assay and tube formation assay compared to vehicle or calcineurin inhibitor (tacrolimus)-treated cells. Sirolimus also reduced LDL uptake in iPSC-derived endothelial cells compared to vehicle or tacrolimus-treated cells. Tacrolimus was associated with a trend towards altered endothelial energetics. Tacrolimus and sirolimus exert differential endothelial cell functional profiles that do not fully explain the clinical outcomes observed suggesting a need to explore the drug endothelial profiles in the context of vascular injury and inflammation.

MAML3-fusions modulate vascular and immune tumour microenvironment and confer high metastatic risk in pheochromocytoma and paraganglioma

Pheochromocytomas and paragangliomas are rare neuroendocrine tumours. Around 20-25% of patients develop metastases, for which there is an urgent need of prognostic markers and therapeutic stratification strategies. The presence of a MAML3-fusion is associated with increased metastatic risk, but neither the processes underlying disease progression, nor targetable vulnerabilities have been addressed. We have compiled a cohort of 850 patients, which has shown a 3.65% fusion prevalence and represents the largest MAML3-positive series reported to date. While MAML3-fusions mainly cause single pheochromocytomas, we also observed somatic post-zygotic events, resulting in multiple tumours in the same patient. MAML3-tumours show increased expression of neuroendocrine-to-mesenchymal transition markers, MYC-targets, and angiogenesis-related genes, leading to a distinct tumour microenvironment with unique vascular and immune profiles. Importantly, our findings have identified MAML3-tumours specific vulnerabilities beyond Wnt-pathway dysregulation, such as a rich vascular network, and overexpression of PD-L1 and CD40, suggesting potential therapeutic targets.

The BCR::ABL1 tyrosine kinase inhibitors ponatinib and nilotinib differentially affect endothelial angiogenesis and signalling.

BCR::ABL1 inhibitors, the treatment of choice for the majority of patients with chronic myeloid leukaemia (CML), can cause vascular side effects that vary between agents. The exact underlying mechanisms are still poorly understood, but the vascular endothelium has been proposed as a site of origin. The present study investigates the effects of three BCR::ABL1 inhibitors, ponatinib, nilotinib and imatinib, on angiogenesis and signalling in human endothelial cells in response to vascular endothelial growth factor (VEGF). The experiments were performed in endothelial cells isolated from human umbilical veins. After exposure to imatinib, ponatinib and nilotinib, the angiogenic capacity of endothelial cells was assessed in spheroid assays. VEGF-induced signalling pathways were examined in Western blotting experiments using different specific antibodies. RNAi technology was used to downregulate proteins of interest. Intracellular cGMP levels were measured by ELISA. Imatinib had no effect on endothelial function. Ponatinib inhibited VEGF-induced sprouting, while nilotinib increased spontaneous and VEGF-stimulated angiogenesis. These effects did not involve wild-type ABL1 or ABL2, as siRNA-mediated knockdown of these kinases did not affect angiogenesis and VEGF signalling. Consistent with their effects on sprouting, ponatinib and nilotinib affected angiogenic pathways in opposite directions. While ponatinib inhibited VEGF-induced signalling and cGMP formation, nilotinib activated angiogenic signalling, in particular phosphorylation of extracellular signal-regulated kinase 1/2 (Erk1/2). The latter occurred in an epidermal growth factor receptor (EGFR)-dependent manner possibly via suppressing Fyn-related kinase (FRK), a negative regulator of EGFR signalling. Both, pharmacological inhibition of Erk1/2 or EGFR suppressed nilotinib-induced angiogenic sprouting. These results support the notion that the vascular endothelium is a site of action of BCR::ABL1 inhibitors from which side effects may arise, and that the different vascular toxicity profiles of BCR::ABL1 inhibitors may be due to their different actions at the molecular level. In addition, the as yet unknown pro-angiogenic effect of nilotinib should be considered in the treatment of patients with comorbidities associated with pathological angiogenesis, such as ocular disease, arthritis or obesity.

Activation of the hypoxia response in the aging cerebrovasculature protects males against cognitive impairment.

Alzheimer's disease (AD) is a neurodegenerative disorder with a distinct sex bias. Age-related vascular alterations, a hallmark of AD onset and progression, are consistently associated with sexual dimorphism. Here, we conducted an integrative meta-analysis of 335,803 single-nucleus transcriptomes and 667 bulk transcriptomes from the vascular system in AD and normal aging to address the underlying sex-dependent vascular aging in AD. All vascular cell types in male AD patients exhibited an activated hypoxia response and downstream signaling pathways including angiogenesis. The female AD vasculature is characterized by increased antigen presentation and decreased angiogenesis. We further confirmed that these sex-biased alterations in the cerebral vascular emerged and were primarily determined in the early stages of AD. Sex-stratified analysis of normal vascular aging revealed that angiogenesis and various stress-response genes were downregulated concurrently with female aging. Conversely, the hypoxia response increased steadily in males upon aging. An investigation of upstream driver transcription factors (TFs) revealed that altered communication between estrogen receptor alpha (ESR1) and hypoxia induced factors during menopause contributes to the inhibition of angiogenesis during normal female vascular aging. Additionally, inhibition of CREB1, a TF that targets estrogen, is also related to female AD. Overall, our study revealed a distinct cerebral vascular profile in females and males, and revealed novel targets for precision medicine therapy for AD.

Vascular biomarkers reveal a unique toxicity profile of posttransplant cyclophosphamide: secondary analysis of BMT CTN 0402 and 1202

AbstractPosttransplant cyclophosphamide (PTCy)–based graft-versus-host disease (GVHD) prophylaxis regimens are associated with very low rates of severe acute and chronic GVHD after hematopoietic cell transplant (HCT). However, concerns about cardiac and other organ toxicities persist. This study aimed to compare the vascular biomarker profile of PTCy with other GVHD regimens, including tacrolimus/sirolimus (Tac/Sir) and tacrolimus/methotrexate (Tac/MTX), to generate hypotheses for toxicity mitigation strategies. Plasma samples from day +28 after transplant were analyzed against pretransplant baseline measurements in patients receiving PTCy-based GVHD prophylaxis as part of Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 1202 (n = 112) vs Tac/MTX (n = 98) and Tac/Sir (n = 95) regimens from BMT CTN 0402. Compared with Tac/MTX, PTCy was associated with increasing angiopoietin-2 levels and decreasing epidermal growth factor levels at day +28. In contrast, Tac/Sir displayed increasing follistatin and endoglin levels and decreasing vascular endothelial growth factor receptor 2 (VEGFR2) plasma levels after HCT. Across all cohorts, increasing epidermal growth factor was protective from nonrelapse mortality, and decreasing VEGFR2 was associated with subsequent development of extensive chronic GVHD. These distinct biomarker profiles offer insights that could guide strategies to mitigate unique GVHD prophylaxis–associated toxicities.

The Role of Local Flaps in Foot and Ankle Reconstruction: An Assessment of Outcomes Across 206 Patients with Chronic Wounds.

Reconstructive surgery has experienced a paradigm shift in favor of free flaps. Yet, local flaps may be of particular use in foot and ankle reconstruction among comorbid patient populations. Thus, we sought to better characterize long-term outcomes in this setting. A single-center, retrospective cohort study of patients undergoing local muscle and fasciocutaneous flaps of the foot and ankle from January 2010-November 2022 was performed. Flap were performed on wounds measuring 3x6cm or smaller, and flap selection depended on preoperative vascular assessment, Doppler findings, comorbidity profile, and wound location, depth, and geometry. Two-hundred and six patients met inclusion criteria. Median age was 61.0 years (IQR 16.8), and comorbidities included diabetes mellitus (DM; n=149/206, 72.3%) and peripheral arterial disease (PAD; n=105/206, 51.0%). Presentations included chronic, non-healing wounds (n=77/206, 39.1%) or osteomyelitis (n=45/206, 22.8%), and most frequently extended to the bone (n=128/206, 62.1%). Eighty-seven patients (n=87/206, 42.2%) received muscle flaps, while 119 received fasciocutaneous flaps (n=119/206, 57.8%). Six patients (n=6/206, 2.9%) necessitated return to the operating room, with thrombosis occurring in two cases (n=2/206, 1.0%). Flap success rate was 98.1%. By a median follow-up duration of 21.7 months (IQR 39.0), 45 patients (n=45/206, 21.8%) necessitated ipsilateral amputation, 73% (n=145/199) were ambulatory, and two deaths were related to the operated wound (n=2/49, 4.1%). Multivariate analysis revealed positive predictors of complications included DM, end-stage renal disease, and prior histories of venous thromboembolism or smoking. Local flaps remain a reliable option to reconstruct smaller defects of the foot and ankle in a highly comorbid population.

Vascular risk profile and changes of arterial hypertension after surgical revascularization in adult Moyamoya patients

Moyamoya disease (MMD) is a rare stenoocclusive cerebral vasculopathy often treated by neurosurgical revascularization using extracranial-intracranial bypasses to prevent ischemic or hemorrhagic events. Little is known about the vascular risk profile of adult MMD patients compared to the general population. We therefore analyzed 133 adult MMD patients and compared them with data from more than 22,000 patients from the German Health Update database. Patients with MMD showed an age- and sex-adjusted increased prevalence of arterial hypertension, especially in women between 30 and 44 years and in patients of both sexes between 45 and 64 years. Diabetes mellitus was diagnosed significantly more frequently in MMD patients with increasing age, whereas the vascular risk profile in terms of obesity, nicotine and alcohol consumption was similar to that of the general population. Antihypertensive medication was changed one year after surgical revascularization in 67.5% of patients with a tendency towards dose reduction in 43.2% of all patients. After revascularization, physicians need to be aware of a high likelihood of changes in arterial hypertension and should adjust all other modifiable systemic vascular risk factors to achieve the best treatment possible.

Identifying Giant Cell Arteritis patients with higher risk of relapse and vascular events: a cluster analysis.

Giant cell arteritis (GCA) is one of the most common large vessel (LVV) vasculitis and is associated with a high risk of relapse and cardiovascular complications. Improving risk stratification remains a significant issue in this patient population. We aimed to perform a cluster analysis among GCA to identify clusters and evaluate their prognostic value. In a multicenter cohort study, we performed hierarchical cluster analysis on the factor analysis of mixed data coordinates results with 283 GCA patients' characteristics to generate clusters and assess incidence of relapse, cardiovascular events and death. Three clusters were identified: "Vascular relapsing profile" (23.0%), "Typical GCA profile" (47.7%), and "Ophthalmologic elderly profile" (29.3%). The "Vascular relapsing profile" cluster included younger patients with more frequent relapses and cardiovascular events, particularly thoracic aortic aneurysms. The "Typical GCA profile" was the largest, with classic cranial manifestations and frequently associated polymyalgia rheumatica. The "Ophthalmologic elderly profile" had the oldest patients with more visual loss and the highest mortality rate. Our findings underline the varied prognostic landscape within GCA, emphasizing the poor cardiovascular prognosis of younger patients with LV involvement and the higher mortality among elderly patients. This reinforces the need for further research regarding the screening of aortic abnormalities and whether those patients might benefit from intensive treatment with biotherapy and cardiovascular risk factors management.

#331 Vascular and lipid profile interplays in pediatric CKD patients

Abstract Background and Aims Chronic kidney disease (CKD) is characterized by irreversible kidney damage and/or progressive loss of function. Children with CKD often have additional CVD risk factors, including hypertension and dyslipidemia. They may have myocardial abnormalities and early atherosclerosis evidence, such as coronary artery calcification, abnormal flow-mediated dilation, increased carotid intima-medial thickness (CIMT), and increased aortic stiffness. These abnormalities seem to be, in part, related to the degree of uremia. This study aimed at assessing the interrelationship between vascular status and lipid profile abnormalities in different stages of CKD in pediatric patients. Method This cross-sectional study was done on 99 patients: 33 with stage 5 CKD on regular hemodialysis &amp; 33 pre-dialysis CKD stage 2-4 on conservative management &amp; 33 age and sex matched controls. Anthropometric measures, blood pressure readings, and a lipid profile were done to all groups. Intima media thickness was measured using B-mode ultrasound doppler in both the common and internal carotid arteries (CCA, ICA). Which is a non-invasive way to measure the artery walls and track the early impacts of the atherosclerotic process. Results There was an obvious increase in blood pressure the percentiles in all CKD patients in relation to controls. The waist-to-hip ratio in CKD 2-4 patients was significantly higher than in CKD 5 patients, and both were higher than the controls, with means (±SD) of 1.01 (0.19), 0.88 (0.10), and 0.86 (0.05), respectively. Except for high-density lipoproteins (HDL), the lipid profile, including triglycerides, cholesterol, and low-density lipoproteins (LDL), were all significantly increased when comparing CKD 2-4 to CKD 5, and both higher than the controls: 170.45 (42.04), 166.00 (45.57), and 100.88 (26.19) for triglycerides (p 0.001). The right and left ICA and CCA showed a significant increase in the intimal thickness being higher in the CKD 5 group than the CKD 2-4 and both higher than the controls. On studying the correlation between the duration of CKD in years and other variables, we found a positive correlation with triglycerides (r = 0.409 &amp; p = 0.001) and right CCA IMT (r = 0.271 &amp; p = 0.028); however, the HDL (r = −0.326 &amp; p = 0.007) revealed a negative correlation in all CKD patients. The HDL level showed an inverse correlation with right CCA and ICA. Conclusion Patients with CKD have an increased waist-to-hip ratio, dyslipidemia, and increased carotid IMT, which are factors that lead to the early development of atherosclerosis. Special care should be directed to CKD patients, especially those in stages 2-4, to control their lipid profile and postpone the development of atherosclerosis as much as possible.

Comparison of vascular risk profile and clinical outcomes among patients with central (branch) retinal artery occlusion versus amaurosis fugax

BackgroundRetinal artery occlusions lead to sudden, painless vision loss, affecting millions globally. Despite their significance, treatment strategies remain unestablished, contrasting with acute ischemic stroke (AIS), where IVT has proven efficacy. Similar to AIS, retinal artery occlusions demand urgent evaluation and treatment, reflecting the principle "time is retina". Even for patients with transient monocular vision loss, also known as amaurosis fugax (AF), pertinent guidelines meanwhile recommend immediate emergency assessment in a specialized facility. However, data on the clinical benefit and comparability with persistent occlusions are missing. This study aimed to compare the results of a comprehensive stroke-workup among patients with persistent retinal artery occlusions (RAO), including both central retinal (CRAO) and branch retinal artery occlusion (BRAO) and those with AF.MethodsConducted at the University Hospital Giessen, Germany, this exploratory cross-sectional study enrolled patients with transient or permanent unilateral vision loss of non-arteritic origin. The primary outcome were differences between the two groups RAO and AF with regard to cardiovascular risk profiles and comorbidities, vascular and pharmacological interventions and clinical neurological and ophthalmological outcomes. Secondary outcome was a sub-group analysis of patients receiving IVT.ResultsOut of 166 patients assessed, 76 with RAO and 40 with AF met the inclusion criteria. Both groups exhibited comparable age, gender distribution, and cardiovascular risk profiles. Notably, RAO patients did not show significantly more severe vascular comorbidities than AF patients. However, AF patients received vascular interventions more frequently. Pharmacological intervention rates were similar across groups. RAO patients had slightly worse neurological outcomes, and IVT did not yield favorable ophthalmological outcomes within any observed patients.ConclusionThe study found similar vascular burden and risk factors in patients with RAO and AF, with implications for clinical workflows. IVT for RAO may only be effective in very early treatment windows. This emphasizes the need for public awareness and collaborative protocols between ophthalmologists and neurologists to improve outcomes.

Secondary Prevention in Patients With Stroke Versus Myocardial Infarction: Analysis of 2 National Cohorts.

The implementation of preventive therapies among patients with stroke remains inadequately explored, especially when compared with patients with myocardial infarction (MI), despite sharing similar vascular risk profiles. We tested the hypothesis that participants with a history of stroke have a worse cardiovascular prevention profile in comparison to participants with MI. In cross-sectional analyses within the UK Biobank and All of Us Research Program, involving 14 760 (9193 strokes, 5567 MIs) and 7315 (2948 strokes, 4367 MIs) participants, respectively, we evaluated cardiovascular prevention profiles assessing low-density lipoprotein (<100 mg/dL), blood pressure (systolic, <140 mm Hg; and diastolic, <90 mm Hg), statin and antiplatelet use, and a cardiovascular prevention score that required meeting at least 3 of these criteria. The results revealed that, within the UK Biobank, patients with stroke had significantly lower odds of meeting all the preventive criteria compared with patients with MI: low-density lipoprotein control (odds ratio [OR], 0.73 [95% CI, 0.68-0.78]; P<0.001), blood pressure control (OR, 0.63 [95% CI, 0.59-0.68]; P<0.001), statin use (OR, 0.45 [95% CI, 0.42-0.48]; P<0.001), antiplatelet therapy use (OR, 0.30 [95% CI, 0.27-0.32]; P<0.001), and cardiovascular prevention score (OR, 0.42 [95% CI, 0.39-0.45]; P<0.001). Similar patterns were observed in the All of Us Research Program, with significant differences across all comparisons (P<0.05), and further analysis suggested that the odds of having a good cardiovascular prevention score were influenced by race and ethnicity as well as neighborhood deprivation levels (interaction P<0.05 in both cases). In 2 independent national cohorts, patients with stroke showed poorer cardiovascular prevention profiles and lower adherence to guideline-directed therapies compared with patients with MI. These findings underscore the need to explore the reasons behind the underuse of secondary prevention in vulnerable stroke survivors.

Development of an Automated Morphometric Approach to Assess Vascular Outcomes following Exposure to Environmental Chemicals in Zebrafish.

Disruptions in vascular formation attributable to chemical insults is a pivotal risk factor or potential etiology of developmental defects and various disease settings. Among the thousands of chemicals threatening human health, the highly concerning groups prevalent in the environment and detected in biological monitoring in the general population ought to be prioritized because of their high exposure risks. However, the impacts of a large number of environmental chemicals on vasculature are far from understood. The angioarchitecture complexity and technical limitations make it challenging to analyze the entire vasculature efficiently and identify subtle changes through a high-throughput in vivo assay. We aimed to develop an automated morphometric approach for the vascular profile and assess the vascular morphology of health-concerning environmental chemicals. High-resolution images of the entire vasculature in Tg(fli1a:eGFP) zebrafish were collected using a high-content imaging platform. We established a deep learning-based quantitative framework, ECA-ResXUnet, combined with MATLAB to segment the vascular networks and extract features. Vessel scores based on the rates of morphological changes were calculated to rank vascular toxicity. Potential biomarkers were identified by vessel-endothelium-gene-disease integrative analysis. Whole-trunk blood vessels and the cerebral vasculature in larvae exposed to 150 representative chemicals were automatically segmented as comparable to human-level accuracy, with sensitivity and specificity of 95.56% and 95.81%, respectively. Chemical treatments led to heterogeneous vascular patterns manifested by 31 architecture indexes, and the common cardinal vein (CCV) was the most affected vessel. The antipsychotic medicine haloperidol, flame retardant 2,2-bis(chloromethyl)trimethylenebis[bis(2-chloroethyl) phosphate], and tert-butylphenyl diphenyl phosphate ranked as the top three in vessel scores. Pesticides accounted for the largest group, with a vessel score of , characterized by a remarkable inhibition of subintestinal venous plexus and delayed development of CCV. Multiple-concentration evaluation of nine per- and polyfluoroalkyl substances (PFAS) indicated a low-concentration effect on vascular impairment and a positive association between carbon chain length and benchmark concentration. Target vessel-directed single-cell RNA sequencing of cells from larvae treated with , perfluorohexanesulfonic acid, or benzylbutyl phthalate, along with vessel-endothelium-gene-disease integrative analysis, uncovered potential associations with vascular disorders and identified biomarker candidates. This study provides a novel paradigm for phenotype-driven screenings of vascular-disrupting chemicals by converging morphological and transcriptomic profiles at a high-resolution level, serving as a powerful tool for large-scale toxicity tests. Our approach and the high-quality morphometric data facilitate the precise evaluation of vascular effects caused by environmental chemicals. https://doi.org/10.1289/EHP13214.

Racial-Ethnic disparities in stroke prevalence among patients with heart failure

Racial-ethnic disparities exist in the prevalence and outcomes of heart failure (HF) and are presumed to be related to differences in cardiovascular risk factor burden and control. There is little data on stroke disparities among patients with HF or the factors responsible. We hypothesized disparities in stroke prevalence exist among patients with HF in a manner not fully explained by burden of cardiovascular disease. We analyzed data from the National Health and Nutrition Examination Survey (1999–2014). Cardiovascular profiles were compared by race/ethnicity. Using survey-weighted models, effect modification of the relationship between HF and stroke by race/ethnicity was examined adjusting for cardiovascular profiles. Of 40,437 participants, 2.5 % had HF. The HF cohort had a greater proportion of White and Black participants (77 % vs 74 % and 15 % vs 12 %, respectively) and fewer participants of Hispanic ethnicity (8 % vs 14 %). Stroke was 8 times more prevalent in HF (19.6 % vs 2.3 %, <0.001). Among individuals with HF, race-ethnic differences were identified in the prevalence and mean values of vascular risk factors but were largely driven by higher rates in Black participants. There was significant interaction between HF and race/ethnicity; HF increased the odds of stroke over 7-fold in participants of Hispanic ethnicity (aOR: 7.84; 95 % CI: 4.11–15.0) but to a lesser extent in Black and White participants (Black aOR: 2.49; 95 % CI: 1.72–3.60; White aOR: 3.36; 95 % CI: 2.57–4.40). People of Hispanic ethnicity with HF have a disproportionately higher risk of stroke in a manner not fully explained by differences in vascular risk profiles.

Associations of sleep disorders with all-cause MCI/dementia and different types of dementia - clinical evidence, potential pathomechanisms and treatment options: A narrative review.

Due to worldwide demographic change, the number of older persons in the population is increasing. Aging is accompanied by changes of sleep structure, deposition of beta-amyloid (Aß) and tau proteins and vascular changes and can turn into mild cognitive impairment (MCI) as well as dementia. Sleep disorders are discussed both as a risk factor for and as a consequence of MCI/dementia. Cross-sectional and longitudinal population-based as well as case-control studies revealed sleep disorders, especially sleep-disorderded breathing (SDB) and excessive or insufficient sleep durations, as risk factors for all-cause MCI/dementia. Regarding different dementia types, SDB was especially associated with vascular dementia while insomnia/insufficient sleep was related to an increased risk of Alzheimer's disease (AD). Scarce and still inconsistent evidence suggests that therapy of sleep disorders, especially continuous positive airway pressure (CPAP) in SDB, can improve cognition in patients with sleep disorders with and without comorbid dementia and delay onset of MCI/dementia in patients with sleep disorders without previous cognitive impairment. Regarding potential pathomechanisms via which sleep disorders lead to MCI/dementia, disturbed sleep, chronic sleep deficit and SDB can impair glymphatic clearance of beta-amyloid (Aß) and tau which lead to amyloid deposition and tau aggregation resulting in changes of brain structures responsible for cognition. Orexins are discussed to modulate sleep and Aß pathology. Their diurnal fluctuation is suppressed by sleep fragmentation and the expression suppressed at the point of hippocampal atrophy, contributing to the progression of dementia. Additionally, sleep disorders can lead to an increased vascular risk profile and vascular changes such as inflammation, endothelial dysfunction and atherosclerosis which can foster neurodegenerative pathology. There is ample evidence indicating that changes of sleep structure in aging persons can lead to dementia and also evidence that therapy of sleep disorder can improve cognition. Therefore, sleep disorders should be identified and treated early.

Muscle Oxygen Extraction during Vascular Occlusion Test in Physically Very Active versus Inactive Healthy Men: A Comparative Study.

An increase in the delivery and use of oxygen to the musculature in physically active subjects are determinants of improving health-related aerobic capacity. Additional health benefits, such as an increase in the muscle mass and a decrease in fat mass, principally in the legs, could be achieved with weekly global physical activity levels of more than 300 min. The objective was to compare the muscle vascular and metabolic profiles of physically very active and inactive subjects. Twenty healthy men participated in the study; ten were assigned to the physically very active group (25.5 ± 4.2 years; 72.7 ± 8.1 kg; 173.7 ± 7.6 cm) and ten to the physically inactive group (30.0 ± 7.4 years; 74.9 ± 11.8 kg; 173.0 ± 6.4 cm). The level of physical activity was determined by the Global Physical Activity Questionnaire (GPAQ). A resting vascular occlusion test (5 min of an ischemic phase and 3 min of a reperfusion phase) was used, whereas a near-field infrared spectroscopy (NIRS) device was used to evaluate the muscle oxygenation in the right vastus lateralis of the quadriceps muscle. The area under the curve of the deoxyhemoglobin (HHb) during the ischemic phase and above the curve of the tissue saturation index (TSI) during the reperfusion phase were obtained to determine muscle metabolic and vascular responses, respectively. Physically very active group showed a higher absolute HHb (3331.9 ± 995.7 vs. 6182.7 ± 1632.5 mmol/s) and lower TSI (7615.0 ± 1111.9 vs. 5420.0 ± 781.4 %/s) and relative to body weight (46.3 ± 14.6 vs. 84.4 ± 27.1 mmol/s/kg and 106.0 ± 20.6 vs. 73.6 ± 13.8 %/s/kg, respectively), muscle mass (369.9 ± 122.2 vs. 707.5 ± 225.8 mmol/kg and 829.7 ± 163.4 vs. 611.9 ± 154.2 %/s/kg) and fat mass (1760.8 ± 522.9 vs. 2981.0 ± 1239.9 mmol/s/kg and 4160.0 ± 1257.3 vs. ±2638.4 ± 994.3 %/s/kg, respectively) than physically inactive subjects. A negative correlation was observed between HHb levels and TSI (r = -0.6; p < 0.05). Physically very active men (>300 min/week) present better muscle oxidative metabolism and perfusion and perform significantly more physical activity than physically inactive subjects. Extra benefits for vascular health and muscle oxidative metabolism are achieved when a subject becomes physically very active, as recommended by the World Health Organization. In addition, a higher level of physical activity determined by GPAQ is related to better vascular function and oxidative metabolism of the main locomotor musculature, i.e., the quadriceps.

Denoising parameter dependence of coronary artery depictability in compressed sensing magnetic resonance angiography.

Using numerical indices and visual evaluation, we evaluated the dependence of coronary-artery depictability on the denoising parameter in compressed sensing magnetic resonance angiography (CS-MRA). This study was conducted to clarify the acceleration factor (AF) and denoising factor (DF) dependence of CS-MRA image quality. Vascular phantoms and clinical images were acquired using three-dimensional CS-MRA on a clinical 1.5T system. For the phantom measurements, we compared the full width at half maximum (FWHM), sharpness, and contrast ratio of the vascular profile curves for various AFs and DFs. In the clinical cases, the FWHM, sharpness, contrast ratio, signal-to-noise ratio, noise level values, and visual evaluation results were compared for various DFs. Phantom image analyses demonstrated that the respective measurements of the FWHM, sharpness, and contrast ratios did not significantly change with an increase in AF. The FWHM and sharpness measurements slightly changed with the DF level. However, the contrast ratio tended to increase with an increase in the DF level. In the clinical cases, the FWHM and sharpness showed no significant differences, even when the DF level was changed. However, the contrast ratio tended to decrease as the DF level increased. When the DF levels of the clinical cases increased, the background signals of the myocardium, fat, and noise levels decreased. We investigated the dependence of the coronary-artery depictability on AF and DF using CS-MRA. Analysis of the coronary-artery profile curves indicated that a better image quality was achieved with a stronger DF on coronary CS-MRA.

Risk factors for intracerebral hemorrhage in small-vessel disease and non-small-vessel disease etiologies-an observational proof-of-concept study.

Sporadic cerebral small-vessel disease (CSVD), i.e., hypertensive arteriopathy (HA) and cerebral amyloid angiopathy (CAA), is the main cause of spontaneous intracerebral hemorrhage (ICH). Nevertheless, a substantial portion of ICH cases arises from non-CSVD etiologies, such as trauma, vascular malformations, and brain tumors. While studies compared HA- and CAA-related ICH, non-CSVD etiologies were excluded from these comparisons and are consequently underexamined with regard to additional factors contributing to increased bleeding risk beyond their main pathology. As a proof of concept, we conducted a retrospective observational study in 922 patients to compare HA, CAA, and non-CSVD-related ICH with regard to factors that are known to contribute to spontaneous ICH onset. Medical records (available for n = 861) were screened for demographics, antithrombotic medication, and vascular risk profile, and CSVD pathology was rated on magnetic resonance imaging (MRI) in a subgroup of 185 patients. The severity of CSVD was assessed with a sum score ranging from 0 to 6, where a score of ≥2 was defined as advanced pathology. In 922 patients with ICH (median age of 71 years), HA and CAA caused the majority of cases (n = 670, 73%); non-CSVD etiologies made up the remaining quarter (n = 252, 27%). Individuals with HA- and CAA-related ICH exhibited a higher prevalence of predisposing factors than those with non-CSVD etiologies. This includes advanced age (median age: 71 vs. 75 vs. 63 years, p < 0.001), antithrombotic medication usage (33 vs. 37 vs. 19%, p < 0.001), prevalence of vascular risk factors (70 vs. 67 vs. 50%, p < 0.001), and advanced CSVD pathology on MRI (80 vs. 89 vs. 51%, p > 0.001). However, in particular, half of non-CSVD ICH patients were either aged over 60 years, presented with vascular risk factors, or had advanced CSVD on MRI. Risk factors for spontaneous ICH are less common in non-CSVD ICH etiologies than in HA- and CAA-related ICH, but are still frequent. Future studies should incorporate these factors, in addition to the main pathology, to stratify an individual's risk of bleeding.