Endothelial Function Parameters Research Articles

NOX2 as a Biomarker of Academic Performance: Evidence from University Students during Examination.

Cortisol levels, oxidative stress, and lower cerebral performance seem to be closely related. This study aimed to evaluate the question of whether exam stress affected oxidative stress and endothelial function parameters in the salivary samples of students. A total of 114 healthy students were recruited. All students were subjected to a 21-item DASS questionnaire to assess perceived stress. Cortisol levels, biomarkers of oxidative stress, and endothelial function were evaluated at T0, during the semester, and T1, in the morning before the exam, in saliva samples. In vitro, HUVECs were stimulated with cortisol, and oxidative stress and endothelial function parameters were evaluated. At T1, cortisol levels were significantly increased compared with the levels during the semester. Moreover, exam results correlated inversely with the DASS score at T1. In addition, NOX2, H2O2 and endothelin-1 significantly increased, while NO bioavailability decreased. In vitro, HUVECs treatment with human cortisol determined the increase of oxidative stress and the decrease of endothelial function, in association with impaired eNOS phosphorylation. NOX2-mediated oxidative stress is a mechanism that could mediate cortisol-induced transient endothelial dysfunction during academic examination. Therefore, strategies to monitor or modulate oxidative stress could help students to reduce the impact of examination-related stress.

Endothelial function in patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors is not related to cardiovascular risk assessed by the Systematic Coronary Risk Estimation 2 algorithm.

Tyrosine kinase inhibitors (TKIs) revolutionized treatment of chronic myeloid leukemia (CML), but are endowed with negative effects on endothelial function. We aimed to characterize endothelial function in patients with CML treated with various TKIs. A total of 48 patients diagnosed with chronic‑phase CML treated with TKIs, such as imatinib, bosutinib, nilotinib, ponatinib, and asciminib were included. Endothelial function was assessed in the brachial artery and microcirculation based on flow‑mediated dilation (FMD), reactive hyperemia peripheral arterial tonometry (RH‑PAT) and flow‑mediated skin fluorescence (FMSF). Reactive hyperemia index, FMD, reactive hyperemia response (RHR), normoxia oscillatory index, and hyperemic response index did not differentiate between the group of patients with low / moderate risk in the Systematic Coronary Risk Estimation 2 (SCORE2), SCORE2‑Older Persons (SCORE2‑OP), and those with high / very high risk scores. Among the patients with low / intermediate risk based on the SCORE2 algorithm, some had lower (below the first quartile) values of the endothelial parameters, reflecting impaired endothelial function, as compared with the high / very high risk patient population. Lower values of the endothelial function parameters were associated with overall long‑term treatment with TKIs or ponatinib. Importantly, endothelial function assessed by FMSF (RHR) negatively correlated with total duration of TKI treatment, also after adjustment for age. Endothelial function in CML patients treated with TKIs was not related to cardiovascular risk based on SCORE2/SCORE2‑OP algorithms but correlated with CML‑specific factors, including duration of TKI treatment. FMSF‑based assessment of skin microcirculation was a sensitive method for detecting the vascular effects of TKIs.

(134) Early Impact of Androgen Deprivation Therapy on Endothelial Function and Metabolic Parameters in Prostate Cancer Patients: A Prospective Study

Abstract Introduction Androgen deprivation therapy (ADT) is considered one of the mainstays in the treatment of prostate cancer. ADT slows cancer progression, alleviates cancer-related symptoms, and is associated with survival gains. Despite these proven benefits, this treatment is related to several side effects, such as increased cardiovascular risk, changes in body composition and various metabolic changes. Although the well-established association between circulating testosterone level and endothelial integrity, the direct effects of ADT on endothelial function remain controversial. Objective This study aimed to investigate the impact of ADT on endothelial function, through the analysis of vascular parameters of the brachial artery and measurement of serum inflammatory markers. It was also our aim to evaluate the early impact of ADT on body composition and metabolic parameters. Methods We prospectively evaluated men with moderate to high-risk prostate cancer treated with ADT from January to December 2022 at our institution. Smokers and those who quit smoking less than five years ago, decompensated diabetics (glycated hemoglobin > 9%) and those who had already had a cardiovascular event were excluded. High-resolution B-mode ultrasound was used to assess vascular diameter and endothelium-dependent flow-mediated vasodilation (FMD) of the brachial artery. Our metabolic and inflammatory profile included measurement of serum total cholesterol and fractions, triglycerides, fasting glucose, glycated hemoglobin, basal insulin, C-reactive protein and assessment of body fat distribution through bioelectrical impedance. Subjects were evaluated at baseline and 3 months after starting ADT with goserelin acetate 10.80 mg. Results A total of 32 men were included. The mean age was 69 years and the prevalence of diabetes was 31.25%. FMD demonstrated a worsening trend after ADT, which did not reach statistical significance after 3 months (mean 3.39 ± 6.83 vs 1.16 ± 7.65; p = 0.14) (figure 1). Baseline brachial artery diameter also showed a tendency to worsen with ADT compared to baseline (0.44 ± 0.06 vs 0.42 ± 0.06; p = 0.06). With regard to the metabolic profile, ADT significantly increased insulin resistance: fasting glucose (mean 104.10 ± 18.96 vs 110.60 ± 25.29; p = 0.01), fasting insulin levels (mean 13.05 ± 8.76 vs 16.82 ± 11.36; p = 0.003), glycated hemoglobin (mean 5.89% ± 0.46 vs 6.15% ± 0.67; p = 0.008) and homeostatic model assessment insulin resistance (mean 3.47 ± 2.55 vs 5.05 ± 4.50; p = 0.005) increased significantly after 3 months. Triglycerides concentrations (mean 142.30 ± 69.66 vs 165.50 ± 93.04; p = 0.03) were higher after 3 months of ADT. Abdominal circumference (mean 98.66 ± 10.16 vs 99.76 ± 9.39; p = 0.02) and body mass index (mean 27.46 ± 4.06 vs 27.76 ± 3.89; p = 0.02) also increased after ADT. Conclusions Although not statistically significant, the present study demonstrated a trend towards a decrease in brachial artery FMD. We also observed an important and surprisingly early worsening of the metabolic profile with ADT, especially increased insulin resistance and dyslipidemia, which represent well-established risk factors for cardiovascular events. Disclosure No.

Red Blood Cell Adenylate Energetics Is Related to Endothelial and Microvascular Function in Long COVID.

Adenine nucleotides play a critical role in maintaining essential functions of red blood cells (RBCs), including energy metabolism, redox status, shape fluctuations and RBC-dependent endothelial and microvascular functions. Recently, it has been shown that infection with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) might lead to morphological and metabolic alterations in erythrocytes in both mild and severe cases of coronavirus disease (COVID-19). However, little is known about the effects of COVID-19 on the nucleotide energetics of RBCs nor about the potential contribution of nucleotide metabolism to the long COVID syndrome. This study aimed to analyze the levels of adenine nucleotides in RBCs isolated from patients 12 weeks after mild SARS-CoV-2 infection who suffered from long COVID symptoms and to relate them with the endothelial and microvascular function parameters as well as the rate of peripheral tissue oxygen supply. Although the absolute quantities of adenine nucleotides in RBCs were rather slightly changed in long COVID individuals, many parameters related to the endothelial and microcirculatory function showed significant correlations with RBC adenosine triphosphate (ATP) and total adenine nucleotide (TAN) concentration. A particularly strong relationship was observed between ATP in RBCs and the serum ratio of arginine to asymmetric dimethylarginine-an indicator of endothelial function. Consistently, a positive correlation was also observed between the ATP/ADP ratio and diminished reactive hyperemic response in long COVID patients, assessed by the flow-mediated skin fluorescence (FMSF) technique, which reflected decreased vascular nitric oxide bioavailability. In addition, we have shown that patients after COVID-19 have significantly impaired ischemic response parameters (IR max and IR index), examined by FMSF, which revealed diminished residual bioavailability of oxygen in epidermal keratinocytes after brachial artery occlusion. These ischemic response parameters revealed a strong positive correlation with the RBC ATP/ADP ratio, confirming a key role of RBC bioenergetics in peripheral tissue oxygen supply. Taken together, the outcomes of this study indicate that dysregulation of metabolic processes in erythrocytes with the co-occurring endothelial and microvascular dysfunction is associated with diminished intracellular oxygen delivery, which may partly explain long COVID-specific symptoms such as physical impairment and fatigue.

Association between Inflammation, Glycocalyx Biomarkers, and Endothelial Function in Children with Hypercholesterolemia

Introduction: Hypercholesterolemia is a risk factor for premature arteriosclerosis. Inflammation and oxidative stress are thought to contribute to endothelial dysfunction preceding vasculopathy. We investigated the association between inflammation, glycocalyx biomarkers, endothelial function, and vascular parameters in children with hypercholesterolemia. Methods: In 22 patients (LDL-cholesterol >130 mg/dL; median age [IQR]: 13 [2.3] years) and 22 controls (13 [2.5] years), tumor necrosis factor-alpha (TNF-α), oxidized cholesterol (oxLDL), and glycocalyx biomarkers (Syndecan-1, Hyaluronan) were measured using immunoassays. Endothelial function was assessed by peripheral arterial tonometry, sublingual glycocalyx and microcirculation by videomicroscopy and carotid intima-media thickness by ultrasound. Results: OxLDL was significantly higher in patients (78.9 [38.2] vs. 50.3 [16.6] U/L, p = 0.002), whereas all other experimental parameters were comparable between groups. Multivariate analysis revealed a significant association of Syndecan-1 with TNF-α (β = 0.75, p p = 0.030). The interaction term combining TNF-α and hypercholesterolemia showed a significant effect (p = 0.034). Sex was an independent predictor of endothelial function. Conclusion: The combined effect of hypercholesterolemia and inflammation on glycocalyx perturbation and the impact of sex in the premature development of arteriosclerosis deserve further evaluation. Therapeutic approaches tackling low-grade systemic inflammation may offer potential to prevent or delay progression of cardiovascular disease and cardiovascular complications.

Laboratory evaluation of the hormonal agents effects on the plasma hemostasis system in women of reproductive age

Background: With the evolution of hormonal contraception, such as implementation of low dose agents, new regiments and administration routes of contraceptives, the risk of thrombotic complications persists, although is decreasing. The search for an available test for hemostasis assessment, which would allow for the prediction of thrombotic complications in high risk patients, remains relevant. Global tests for hemostasis assessment, such as thrombin generation test and thrombodynamics test, are attracting the specialists' attention due to the possibility of a quick integrative assessment of plasma hemostasis, especially during choice and tailoring of an optimal version of hormonal therapy.
 Aim: To assess the value of the integral thrombodynamics test in the multifactorial assessment of hemostasis system in women of reproductive age using hormonal contraceptives.
 Materials and methods: This observational prospective comparative study included 408 women aged 18 to 49 years followed from 2018 to 2022 in The Nikiforov Russian Center of Emergency and Radiation Medicine and Centre of Miscarriage Prevention and Treatment of the Maternity Hospital No. 1, St. Petersburg. From these, 208 women (mean age, 38.0 ± 7.0 years) were taking hormonal contraceptives (HC+ group), and 200 women (mean age, 37.5 ± 9.2 years) were in the control group (HC-). In the HC+ group, 163 women were taking combination oral contraceptives, 24 had an intrauterine levonorgestrel-releasing system, 8 used vaginal rings, and 13 were using progestin only oral contraceptives. Multifactorial clinical and laboratory assessment included taking past history, measurement of pro- and anticoagulation blood parameters, fibrinolysis, and endothelial function parameters (automatic coagulometer ACL TOP 500, Instrumentation Laboratory, USA). The integral assessment of the hemostasis system was performed with Thrombodynamics Registrator T-2 (Hemacor, Russia).
 Results: The groups were similar as per their age, chronic venous insufficiency and smoking. The HC+ group had significantly higher proportion of women with cardiovascular disorders (p = 0.0037), obesity (p = 0.0004), and headache (p 0.0001), compared to the HC- group. The thrombodynamics test showed a significantly higher rate of clot formation in the women taking hormonal contraception, compared to that in the HC- group (36.2 [30.1; 43.6] and 30.3 [28.0; 33.6] mcm/min, respectively, р 0.001). Hypercoagulation identified by the thrombodynamics test was associated with slowing down of XIIа-dependent fibrinolysis (6 [5; 8] min in the HC- and 12.8 [8; 16] min in the HC+ group, p 0,001) and higher levels of endothelial dysfunction markers (FVIII, 113 [85; 156] and 150 [107; 180]%, p = 0.015; vFW, 98 [85; 133] and 146 [95; 168]%, respectively, p = 0.003). The analysis of plasma hemostasis parameters depending on the presence of thromboembolic risk factors has shown that higher number of the risk factors is associated with higher velocity parameters in the thrombodynamics test in the range of chronometric hypercoagulation.
 Conclusion: The integral thrombodynamics test for the assessment of plasma hemostasis allows for identification of hemostasis dysfunction in women taking hormonal contraceptives. To prevent the risk of thromboembolic complications, it is desirable to assess blood coagulation system parameters before administration of hormonal agents.

Transcranial Electrostimulation as a Non-pharmacological Method of Treating Arterial Hypertension I Degree in young patients

Purpose: The authors determined the efficacy of transcranial electrostimulation (TES) in treating arterial hypertension I degree in young patients and compared it with electrically induced sleep therapy. Materials and Methods: The performed study is a prospective randomized controlled trial that enrolled 212 patients aged 18-20years with arterial hypertension I degree. Patients were divided into two groups. Group 1 consisted of 110 patients who underwent transcranial electrostimulationusing a method developed at the Institute of Physiology named after I. P. Pavlov, Russian Academy of Sciences in Saint Petersburg. Group 2 included 112 patients who underwent electrically induced sleep therapy procedures with the orbital-retro mastoidal technique of electrode application in a "sedative" mode. The control group included 45 patients with normal blood pressure. All patients underwent 24-hour ambulatory blood pressure monitoring, determination of central hemodynamic parameters, diurnal heart rate variability, and endothelial function parameters. Results: As a result of TES therapy in patients significantly decreased the average diurnal SBP and DBP values, pressure load, normalized the diurnal BP profile, AT, and EF values. As a result of electrosleep therapy, average diurnal SBP, and DBP values decreased unreliably, decreased pressure load, and signs of sympathicotonia, but AT and EF values did not change significantly. TES therapy's effectiveness for treating stage 1 hypertension in young patients is significantly higher by 1.9 times in comparison with electrosontherapy. Conclusion: This study has shown that the TES treatment is more effective than traditional non-pharmacological electrosleep therapyin a "sedative" mode. TES normalizes hemodynamics, BP levels, and EF indicators and can be recommended as one of the methods of antihypertensive therapy in young patients.

Arterial structure and function in patients with hemoblastoses before and after high-dose chemotherapy and autologous hematopoietic stem cell transplantation

Background: High dose chemotherapy (HDCT) preceding autologous hematopoietic stem cell transplantation (autoSCT) can be toxic for cardiovascular system, which can be mediated with the development of endothelial dysfunction. No studies on the assessment of arterial stiffness and endothelial function after HDCT and autoSCT have been performed before.
 Aim: To evaluate endothelial function and arterial rigidity parameters by photoplethysmography in patient candidates for HDCT with autoSCT, to identify associated factors and to analyze changes of these parameters over time after HDCT and autoSCT.
 Materials and methods: In this cohort prospective observational study in 71 patients with verified hemoblastosis (mean age 43.8 ± 12.6 years) we assessed endothelial function and stiffness by photoplethysmography (AngioScan-01, Russia) before and after HDCT with autoSCT. Thirty two (32, 45%) patients had multiple myeloma (ММ), 39 (55%), lymphoproliferative disorders (LPD). We measured the stiffness index (SI), reflection index (RI), augmentation index normalized by heart rate of 75 beats per minute (AIp75) and performed the occlusion test with measurement of occlusion index (ОI) and phase shift (PS).
 Results: Mean RI in the total study group before HDCT with autoSCT was increased to RI 34.9% [24.5; 50.6], OI decreased to OI 1.5 [1.25; 1.80], and PS module decreased to PS 6.7 ms [3.9; 8.9]. After HDCT with autoSCT the PS module increased to 8.4 ms [5.0; 12.4] (p = 0.001) and OI increased to 1.7 [1.3; 2.2] (p = 0,007), which indicates an improvement in endothelial function.
 Changes in other parameters of arterial function were non-significant. We also analyzed a selected group of the patients with MM who had higher cardiovascular risk, compared to the LPD patients: they were older (53 vs 36.1 years; p 0.001), had higher rates of arterial hypertension (p 0.001) and diabetes mellitus (p = 0.048). Compared to the LPD patients, the MM patients had higher baseline values of SI (7.5 m/s [7.3; 7.9]), RI (42.9% [32.1; 53.6]), and AIp75 (6.3% [-1.65; 13.8]), indicating higher vascular stiffness. They also had lower PS module values (5.0 ms [2.1; 8.5]). The LPD patients had been more frequently treated with anthracyclines (p 0.001) and radiation (p = 0.002). After HDCT with autoSCT, they had a higher increment of OI, namely, from 1.4 [1.3; 1.8] to 1.7 [1.4; 2.1] (p = 0.003).
 Conclusion: This study was the first to show a high rate of endothelial dysfunction and vascular stiffness abnormalities in patients with hemoblastoses who were candidates for HDCT with autoSCT. After HDCT with autoSCT, changes of endothelial function and stiffness were multidirectional. Despite a significant improvement, endothelial function parameters were not normalized. We were unable to find any predictors of the abnormalities. Thus, the identified baseline abnormalities in stiffness and endothelial function cannot be a contraindication to HDCT with autoSCT.

Improvement of endothelial function parameters during cardiac rehabilitation predicts cardiovascular death and heart failure hospitalization in patients with HFpEF: 3 years follow up

Abstract Purpose To evaluate the effects of cardiac rehabilitation on Dipeptidyl peptidase 4 (DPP4), circulating Insulin-like growth factor binding protein 1 (IGF BP1) levels and circulating blood marker of endothelial function, nitric oxide (NOx) and to assess their prognostic significance on composite endpoint cardiovascular death (CVD) and heart failure (HF) hospitalization. Methods 88 patients (pts) (62,3±5,7 years) with HFpEF who were admitted at residential rehabilitation center were enrolled in the study. All pts underwent a supervised 3 weeks exercise training. At baseline and after 3 weeks values of DPP4, IGF BP1 and NOx were determined and exercise test was performed. Clinical long-term follow-up (3 years) was performed. All medical therapy was documented, and for this analysis, we focused on CVD death and HF hospitalization. Results After follow-up period, 34 (38,6%) patients experienced composite endpoint (CE group: 11 CVD and 23 HF hospitalization), while 54 (61,4%) pts did not report any deterioration in health status (non-CE group). Baseline values of DPP4, IGF BP1 and NOx did not differ between the examined groups. After 3 weeks of exercise training DPP4 decreased significantly in both group (CE group, from 782,14±124,76 to 642,17±110,53 μg/L, p<0,001; non-CE group, from 774,12±98,65 to 554,71±88,12 μg/L, p<0,001); also IGF BP1 (CE group, from 904,77±115,34 to 689,14±96,55 ng/mL, p<0,001; non-CE group from 898,17±108,55 to 558,18±88,62 ng/mL, p<0,001); and NOx increased (CE group, from 35,4±6,5 to 41,4±5,2 µmol/L, p<0,001; non-CE group, from 36,1±5,2 to 47,2±4,7 µmol/L, p<0,001). All second values od DPP4, IGF BP1 and NOx differ significantly between the examined groups (p<0,001 for all). Exercise capacity (METs) has increased significantly in both groups, but second value in CE group was significantly lower than in non-CE group (P<0.001). A positive correlation was found between IGF BP1 decrease and NOx increase (r=0.554, P<0.01), between IGF BP1 decrease and DPP 4 decrease (r=0.685, P<0.01), between IGF BP1 decrease and METs increase (r=0.653, P<0.01), between DPP4 decrease and NOx increase (r=0.775, P<0.001), between DPP 4 decrease and METs increase (r=0.708, P<0.01), and between METs increase and NOx increase (r=0.746, P<0.001). After adjusment for age and gender, univaried COX-regression analyses showed that NOx increase (OR 0.832, CI 0.462-0.994, p<0.01), DPP4 decrease (OR 0.718, CI 0.614–0.926, p=0.01), IGF BP1 decrease (OR 0.952, CI 0.889–0.999, p=0.002) and METS increase (OR 0.921, CI 0.774-0.977, p=0.014) significantly predict composite endpoint (CV death and HF hospitalization). Conclusion Residential CV rehabilitation, in patients with HFpEF, improved endothelial function. Pts with higher increase of NOx and METs, and greater reduction in DPP4 and IGF BP1 after 3 weeks of specialized cardiac rehabilitation, during 3 years follow up, were at lower risk of CV death and HF hospitalization.

Association of Vitamin D and Endothelial Function in a Subsample of the Participants in the Longitudinal Study of Adult Health (ELSA-BRASIL)

The Longitudinal Study of Adult Health (ELSA-BRASIL) is a multicentric and multidisciplinary cohort study aimed at investigating the incidence and risk factors of chronic diseases. Vitamin D deficiency has been associated with several comorbidities. In this context, the need to assess the impact of vitamin D on endothelial dysfunction in a large-scale study is justified. Thus, in this study, serum levels of vitamin D were determined by HPLC in 509 participants of the ELSA-BRASIL, and its association with endothelial function parameters by Peripheral Arterial Tonometry (BPA and PATratio). Reduced levels of vitamin D were shown to be associated with indicative measures of worse endothelial function. In the logistic regression model, the variables male sex, white color, increase in age, BMI, triglycerides, and vitamin D<30ng/mL were also indicative of worse endothelial function. In summary, vitamin D has presented an association with endothelial function, which may indicate a protective action of vitamin D to the vascular endothelium.

Influence of a new coronavirus infection on the arterial stiffness in patients with hypertension

Objective. The aim of the study was to compare the parameters of lipid profile, arterial stiffness and endothelial function in patients with arterial hypertension (HTN), examined before the COronaVIrus Disease-2019 (COVID-19) pandemic, and patients with HTN who underwent COVID-19.Design and methods. In total, 133 people were included: 72 patients with HTN examined in 2010–2015, 61 patients with HTN who survived after COVID-19. A biochemical blood test was performed to determine the level of glucose, total cholesterol, triglycerides, and high-density lipoprotein cholesterol. The level of low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol was calculated. The parameters of arterial stiffness were assessed using volume sphygmography, endothelial function was determined based on the values obtained in the sample with post-occlusive reactive hyperemia.Results. According to the results of a biochemical blood test, a significantly higher level of total cholesterol and non-high-density lipoprotein cholesterol was noted in patients with HTN who underwent COVID-19. In the compared groups, comparable indicators of endothelial function were registered with post-occlusive reactive hyperemia. At the same time, according to volume sphygmography, the highest values of arterial stiffness indicators (pulse wave velocity in the aorta, pulse wave velocity in elastic arteries, cardio-ankle vascular index on the right and left) were found in patients with HTN who had undergone COVID-19. A univariate regression analysis was carried out, which confirmed a significant negative effect of the transferred COVID-19 on the parameters of arterial stiffness.Conclusions. Patients with HTN in the post-COVID period represent a particularly vulnerable cohort of the population in terms of the risk of developing and progressing cardiovascular pathology, including vascular events. The inclusion of volume sphygmography in the list of examinations will probably allow early detection of an increase in arterial stiffness with subsequent drug correction.

Retracted: Relationship between Quantitative Parameters of Echocardiography and Vascular Endothelial Function in Patients with Chronic Heart Failure and Its Predictive Value for Short-Term MACE Risk.

[This retracts the article DOI: 10.1155/2021/1985962.].

The Anti-Anginal Efficacy of Bosentan in the Coronary Slow Flow Phenomenon

Background: The Coronary Slow Flow Phenomenon (CSFP) is a coronary microvascular disorder that presents with recurrent angina for which there is no available effective therapy. The vasoconstrictor Endothelin-1 (ET-1) has been implicated in the pathophysiology of the CSFP. This study aimed to determine whether the ET-1 antagonist (Bosentan) is effective in ameliorating angina symptoms in CSFP patients. Methods: Using a randomised, double-blind, placebo-controlled, cross-over trial methodology, the anti-anginal efficacy of Bosentan 125mg bd was assessed in 23 patients with symptomatic CSFP. Study endpoints were measured following 4 weeks of therapy with the primary endpoint being angina frequency. Secondary endpoints included (1) clinical measures of angina and health status, (2) endothelial function parameters, and (3) inflammatory and oxidative stress markers. Results: There was no statistically significant reduction in angina frequency with Bosentan therapy compared to placebo (median angina episodes/4weeks [25-75% IQ]: Bosentan 14[5,36] vs Placebo 25[9,55]) although a trend for improvement in symptoms during the Bosentan phase was observed. Furthermore, Bosentan did not impact on any of the secondary endpoints compared with placebo. Conclusion: Bosentan did not have a major impact on angina frequency in patients with the CSFP. A small anti-anginal effect cannot be excluded and requires a larger trial.

The Anti-Anginal Efficacy of Bosentan in the Coronary Slow Flow Phenomenon

Background: The Coronary Slow Flow Phenomenon (CSFP) is a coronary microvascular disorder that presents with recurrent angina for which there is no available effective therapy. The vasoconstrictor Endothelin-1 (ET-1) has been implicated in the pathophysiology of the CSFP. This study aimed to determine whether the ET-1 antagonist (Bosentan) is effective in ameliorating angina symptoms in CSFP patients. Methods: Using a randomised, double-blind, placebo-controlled, cross-over trial methodology, the anti-anginal efficacy of Bosentan 125mg bd was assessed in 23 patients with symptomatic CSFP. Study endpoints were measured following 4 weeks of therapy with the primary endpoint being angina frequency. Secondary endpoints included (1) clinical measures of angina and health status, (2) endothelial function parameters, and (3) inflammatory and oxidative stress markers. Results: There was no statistically significant reduction in angina frequency with Bosentan therapy compared to placebo (median angina episodes/4weeks [25-75% IQ]: Bosentan 14[5,36] vs Placebo 25[9,55]) although a trend for improvement in symptoms during the Bosentan phase was observed. Furthermore, Bosentan did not impact on any of the secondary endpoints compared with placebo. Conclusion: Bosentan did not have a major impact on angina frequency in patients with the CSFP. A small anti-anginal effect cannot be excluded and requires a larger trial.

Abstract P303: Contribution Of Adrenal Leptin Receptor To The Control Of Aldosterone Synthase Expression And Endothelial Function In Female Mice

While premenopausal women are severally affected by the current obesity epidemic, the mechanisms whereby obesity promotes vascular dysfunction in this population remain ill-defined. We previously demonstrated that the adipokine leptin acts on the adrenal gland to promote aldosterone production and that leptin-mediated aldosterone production impairs endothelial function in female mice only. Herein, we investigated whether these mechanisms are dependent on the presence of leptin receptors (lepR) in adrenal glands. We generated lean female mice exhibiting a selective deficiency in LepR in adrenals (AdKO), and obese mice expressing LepR in adrenal glands (db/ad + ) only. Under baseline conditions, AdKO exhibited no alteration in adrenal CYP11B2, renal renin level, aortic endothelial function (measured by acetylcholine-mediated relaxation), arterial stiffness (pulse wave velocity test, PWV), or metabolic parameters including heart and visceral adipose tissue (VAT) weights, fluid amount, glycemia, and HbA1c. Chronic leptin infusion for a week induced trends towards increases in adrenal CYP11B2 (ΔΔCt 1.10±0.12 vs 2.01±0.51, P=0.077), aldosterone (557±95 vs 918±526 pg/ml, P=0.859), and renin levels in WT. AdKO conferred no protection against any of these changes. Leptin infusion impaired endothelial function in WT (Emax 73.3±3.9 vs 52.8±3.1%, P=0.019), which was exacerbated in AdKO (52.8±3.1 vs 34.3±4.1%, P=0.052). However, leptin infusion did not change PWV in WT (3.93±0.22 vs 4.17±0.32 m/s, P=0.999), but induced a trend towards a decrease in AdKO (4.17±0.32 vs 3.11±0.44 m/s, P=0.228). Restoration of adrenal LepR in db/db mice did not alter CYP11B2 nor aldosterone levels but increased renin (ΔΔCt 1.04±0.11 vs 1.48±0.12, P=0.029), heart weight, VAT weight (5.14±0.29 vs 6.52±0.62 g/g, P=0.052), and HbA1c (5.7±0.2 vs 6.9±0.4 %, P=0.035). Although PWV was worsened in db/ad + (5.40±0.27 vs 6.39±0.49 m/s, P=0.035), db/ad + presented improved relaxation compared to db/db (58.5±5.6 vs 73.0±2.2%, P=0.067), inconsistent with our hypothesis. Collectively these data indicate that adrenal LepR might not directly control adrenal CYP11B2 levels expression but latently contributes to changes in endothelial function and arterial stiffness.

Serum uric acid: a futile bystander in endothelial function?

Purpose This study aims to investigate the relationship between serum uric acid levels and endothelial function, oxidative stress, and hemodynamic parameters, and to determine if uric acid levels provide additional insights beyond traditional factors like ageing and hypertension in volunteers with low cardiovascular risk factors. Serum uric acid is known for its antioxidant properties, but it may also contribute to cardiovascular risk. Materials and Methods The study enrolled 40 male participants, divided into three groups based on age and blood pressure status. Group 1 comprised younger participants, group 2 included older individuals without hypertension, and group 3 consisted of older patients with hypertension. The study assessed endothelial function using laser Doppler imaging and measured acetylcholine- and sodium nitroprusside-induced hyperaemia. The heat microcirculatory response was also examined in the presence of L-NAME, an inhibitor of NOS synthase. The study evaluated oxidative stress and arterial stiffness by measuring allantoin, angiotensin II, Homocitrulline/Lysine, and Chloro-Tyrosine/Tyrosine ratios, as well as by performing non-invasive measurements of aortic augmentation indexes and carotid-femoral pulse wave velocity. Results The study found that uric acid levels did not differ significantly among the three groups. Augmentation indexes increased with ageing, but hypertension did not have an additional effect. Blood pressure and carotid-femoral pulse wave velocity differed among the groups, with the lowest values among younger participants and the highest values among older individuals with hypertension. Allantoin and angiotensin II levels did not differ among the groups. However, Homocitrulline/Lysine and Chloro-Tyrosine/Tyrosine ratios were significantly lower in young subjects. Correlation and multivariable analysis showed that uric acid had no effect on any of the studied parameters. Despite a strong association between ageing and systolic blood pressure with impaired endothelial function, oxidative stress, and arterial stiffness, only ageing retained a significant effect in the multivariable analysis. Conclusion In healthy or hypertensive adults with normal renal function, serum uric acid appears to be a futile bystander in endothelial function, oxidative stress, and arterial stiffness, in contrast to ageing, which reduces NO bioavailability. This study suggests that traditional factors such as ageing and hypertension should be the focus of clinical assessment and management of cardiovascular risk, rather than uric acid levels.

The Effect of Additional Treatment with Empagliflozin or Semaglutide on Endothelial Function and Arterial Stiffness in Subjects with Type 1 Diabetes Mellitus-ENDIS Study.

We investigated the effect of additional treatment with newer antidiabetic drugs on endothelium function and arterial stiffness in subjects with type 1 diabetes mellitus (T1DM) without cardiovascular diseases. A total of 89 participants, all users of CGMS (continuous monitoring glucose system), were randomized into three comparable groups, receiving empagliflozin (E; n = 30), receiving semaglutide (S; n = 30), and a control group (C; n = 29). At baseline and 12 weeks post treatment, we measured FMD (brachial artery flow-mediated dilation) and FBF (forearm blood flow as reactive hyperemia assessed with strain gauge plethysmography) as parameters of endothelial function, as well as pulse wave velocity (PWV) and peripheral resistance as parameters of arterial stiffness. Improvement in FMD was significant in both intervention groups compared to controls (E group 2.0-fold, p = 0.000 and S group 1.9-fold, p = 0.000), with no changes between those two groups (p = 0.745). During the evaluation of FBF, there were statistically insignificant improvements in both therapeutic groups compared to controls (E group 1.39-fold, p = 0.074 and S group 1.22-fold, p = 0.701). In arterial stiffness parameters, improvements were seen only in the semaglutide group, with a decline in peripheral resistance by 5.1% (p = 0.046). We can conclude that, for arterial stiffness, semaglutide seems better, but both drugs positively impact endothelial function and, thus, could also have a protective role in T1DM.

Assessment of endothelial dysfunction and inflammation in type 2 diabetic postmenopausal women

Objective: Vascular complications in type 2 diabetes mellitus are an important cause of morbidity and mortality. Also, endothelial dysfunction arises with vascular ageing during the postmenopausal period. Our objective in this study was to evaluate inflammation and endothelial function parameters and their possible diagnostic roles in type 2 diabetic postmenopausal patients. Material and Methods: The study was conducted on four groups, including type 2 diabetic premenopausal (n:20), non-diabetic premenopausal (n:20), type 2 diabetic postmenopausal (n:20), and non-diabetic postmenopausal subjects (n:20). Serum endothelin-1 (ET-1), endothelial nitric oxide synthetase (eNOS), interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), and chitinase-3-like protein 1 (YKL-40) levels were determined as inflammatory and endothelial function markers using ELISA kits. Results: Serum ET-1, IL-6, and YKL-40 levels were higher in the type 2 diabetic postmenopausal group compared to the non-diabetic premenopausal group (p<0.01, p<0.05, and p<0.01, respectively). ET-1, IL-6, and YKL-40 levels were higher in the type 2 diabetic postmenopausal group compared to the non-diabetic postmenopausal group (p<0.001, p<0.05, and p<0.01 respectively). ROC analysis revealed serum ET-1 (AUC 0.933, sensitivity 87.5%, specificity 85.7%), IL-6 (AUC 0.812, sensitivity 56.3%, specificity 92.8%), and YKL-40 (AUC 0.880, sensitivity 81.2%, specificity 92.8%), as good diagnostic parameters, especially in the type 2 diabetic premenopausal vs. non-diabetic premenopausal cohorts. Conclusion: Serum ET-1, IL-6, and YKL-40 levels were at the highest levels in the 2 diabetic postmenopausal group, and the increase in these markers was remarkable in diabetes compared with menopausal periods. Also, ET-1, IL-6, and YKL-40 were good diagnostic parameters for detecting endothelial function and inflammation in type 2 diabetic postmenopausal and non-diabetic premenopausal cohorts.

Optimal uric acid reduction to improve vascular endothelial function in patients with chronic heart failure complicated by hyperuricemia.

Although an association of serum uric acid levels with endothelial function has been shown in various clinical settings, the optimal treatment target that would benefit vascular endothelial function has not been established. We, therefore, conducted a post hoc analysis of the Excited-UA study to identify an optimal target. Patients (N = 133) with chronic heart failure and comorbid hyperuricemia who enrolled in the Excited-UA study were divided into three tertiles based on their serum uric acid level 24 weeks after initiating xanthine oxidase inhibitor treatment with topiroxostat or allopurinol (i.e., groups with low, moderate, and high uric acid levels). Flow-mediated dilation (FMD) and reactive hyperemia index (RHI) values measured by reactive hyperemia peripheral arterial tonometry (RH-PAT) were compared among groups. The change from baseline in the FMD value 24 weeks after treatment was comparable among the three groups. In contrast, the change from baseline in the RHI was significantly different among the three groups (-0.153 ± 0.073, 0.141 ± 0.081 and -0.103 ± 0.104 in the low, moderate, and high uric acid level groups, respectively, P = 0.032). After adjustment for age, body mass index, and concomitant use of diuretics, which differed among the three groups, the change in the RHI in the moderate uric acid level group tended to be higher than that in the high uric acid level group (P = 0.057) and was significantly higher than that in the low uric acid level group (P = 0.020). These results indicate that targeting excessively low uric acid levels by treatment with xanthine oxidase inhibitors might be less beneficial for improving microvascular endothelial function in patients with chronic heart failure. Comparisons of the changes from baseline in vascular endothelial function parameters at 24 weeks among the 3 groups of low, moderae and high uric acid levels achieved with xanthine oxidase inhibitors. After adjustment for confounding factors, such as age, body mass index and concomitant diuretic use, which showed differences among the 3 groups, the change in RHI in the moderate uric acid level group tended to be higher than that in the high uric acid level group and was significantly higher than that in the low uric acid level group.

Clinical Pediatric Exercise Laboratories, Reactive Balance, Sleep, and Muscle Stimulation Considerations

Clinical Pediatric Exercise Laboratories, Reactive Balance, Sleep, and Muscle Stimulation Considerations