Flow-mediated dilatation facilitates transradial coronary angiography: a comparative study.

Introduction: Radial artery (RA) spasm is demonstrated to be one of the most common complications of transradial approach (TRA). Aim: We hypothesised that radial flow-mediated dilation (FMD) can be used as a preprocedural method to assess the likelihood of arterial spasm. Material and methods: The patients were divided into 2 groups: those with and without flow-mediated RA dilatation. A blood pressure cuff was placed on the upper part of the antecubital region of the patients in the FMD group and inflated for 10 min, allowing the pressure to rise to 30 mm Hg above the systolic blood pressure. RA diameters of the patients in both groups were measured via quantitive coronary angiography method before transradial coronary angiography. Results: A total of 165 patients were included in the study, of whom 64 (38.8%) were women. The median age of the patients was 56 years (48-63). The mean RA diameter was significantly larger in the FMD group (3.44 ±0.48 vs. 2.96 ±0.46 mm, p < 0.001), and the number of punctures required for successful transradial cannulation was found to be significantly higher in the group without FMD (1.55 ±0.7 vs. 1.20 ±0.64; p < 0.001). Linear regression analysis revealed diabetes and FMD as independent predictors of RA diameter. In the diabetic subgroup, RA diameter remained larger in the FMD group (3.00 ±0.35 vs. 2.78 ±0.26, p = 0.036). Radial puncture attempts were significantly higher in the control group compared to the FMD group (1.55 ±0.7 vs. 1.20 ±0.64; p < 0.001). Conclusions: In our study, we demonstrated that FMD created by pressure application significantly increased RA diameter and reduced puncture attempt during TRA.

Age and sex differences in the effects of short- and long-term exposure to air pollution on endothelial dysfunction.

BACKGROUND: The effects of air pollution on endothelial function remain unclear across populations. We aimed to use brachial artery flow-mediated dilatation (FMD) to identify demographic differences in the effects of air pollution exposure on endothelial dysfunction. METHODS: We measured FMD in 850 participants from October 2016 to January 2020. Location-specific concentrations of fine particulate matter < 2.5 µm aerodynamic diameter (PM2.5), inhalable particulate matter < 10 µm aerodynamic diameter (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), and ozone (O3) measured by fixed ambient air monitoring stations were collected for short- and long-term exposure assessment. Multiple linear regression models and restricted cubic splines were used to assess the associations before and after stratification by age and sex. RESULTS: This study eventually included 828 participants [551 (66.5%) younger than 65 years and 553 (66.8%) men]. Each 10 µg/m3 increase in 7-day exposure to PM2.5 and PM10 was significantly linearly associated with a 0.07% (ß = -0.07, 95% CI: -0.13 to -0.004) and 0.05% (ß = -0.05, 95% CI: -0.10 to -0.004) decrease in FMD in the fully adjusted model. After full adjustment, long-term exposure to all air pollutants was significantly associated with impaired FMD. Each 10 µg/m3 increase in long-term exposure to PM2.5 and PM10 was significantly associated with a -0.18% (95% CI: -0.34 to -0.03) and - 0.23% (95% CI: -0.40 to -0.06) change in FMD, respectively. After stratification, the associations of lower FMD with long-term exposure to PM2.5, PM10, SO2, NO2, and CO significantly persisted in men and participants younger than 65 years instead of women or older participants. For short-term exposure, we observed differences consistent with long-term exposure and a stronger effect of 7-day exposure to SO2 in men due to a significant interaction effect. CONCLUSION: Short- and long-term exposure to different air pollutants are strongly associated with decreased endothelial function, and susceptibility to air pollution varies significantly with age and sex.

Effect of Oral Care on Endothelial Dysfunction in Patients with Acute Coronary Syndrome.

Periodontitis is a common chronic infection and is associated with cardiovascular disease. This study evaluated whether basic oral care for periodontal disease could improve endothelial function in patients with acute coronary syndrome (ACS).This study enrolled 54 patients with acute coronary syndrome admitted to Kagoshima City Hospital and who had undergone percutaneous coronary intervention. Flow-mediated endothelium-dependent dilatation (FMD) was measured before discharge (initial FMD) and at 8 months after percutaneous coronary intervention (follow-up FMD). The following periodontal characteristics were measured: periodontal pocket depth (PPD, mm), plaque control record (%), and bleeding on probing (%). All patients received basic oral care instructions from dentists. The oral health condition was generally poor in the participants and there were 24 patients (44.4%) who had severe PPD. Despite the intervention of basic oral care, the periodontal characteristics did not improve during the study period; initial FMD and follow-up FMD did not significantly differ (4.38 ± 2.74% versus 4.56 ± 2.51%, P = 0.562). However, the follow-up FMD was significantly lower in patients with severe PPD (≥ 6.0 mm, n = 24) than in patients without severe PPD (≤ 5.0 mm, n = 30) (FMD: 3.58 ± 1.91% versus 5.37 ± 2.67%, P = 0.007). FMD tended to be worse in patients with severe PPD than in patients without severe PPD (ΔFMD: -0.55 ± 2.12 versus 0.81 ± 2.77 %, P = 0.055). In conclusion, during the use of basic oral care, endothelial function improved in patients without severe PPD, while it worsened in patients with severe PPD.

Arterial function in response to a 50 km ultramarathon in recreational athletes.

This study was performed to determine whether prolonged endurance running results in acute endothelial dysfunction and wave-reflection, as endothelial dysfunction and arterial stiffness are cardiovascular risk factors. Vascular function (conduit artery/macrovascular and resistance artery/microvascular) was assessed in 11 experienced runners (8 males, 3 females) before, during and after a 50 km ultramarathon. Blood pressure (BP), heart rate (HR), wave reflection, augmentation index (AIx) and AIx corrected for HR (AIx75) were taken at all time points-Baseline (BL), following 10, 20, 30 and 40 km, 1 h post-completion (1HP) and 24 h post-completion (24HP). Flow-mediated dilatation (FMD) and inflammatory biomarkers were examined at BL, 1HP and 24HP. Reactive hyperaemia area under the curve (AUC) and shear rate AUC to peak dilatation were lower (∼75%) at 1HP compared with BL (P < 0.001 for both) and reactive hyperaemia was higher at 24HP (∼27%) compared with BL (P = 0.018). Compared to BL, both mean central systolic BP and mean central diastolic BP were 7% and 10% higher, respectively, following 10 km and 6% and 9% higher, respectively, following 20 km, and then decreased by 5% and 8%, respectively, at 24HP (P < 0.05 for all). AIx (%) decreased following 20 km and following 40 km compared with BL (P < 0.05 for both) but increased following 40 km when corrected for HR (AIx75) compared with BL (P = 0.02). Forward wave amplitude significantly increased at 10 km (15%) compared with BL (P = 0.049), whereas backward wave reflection and reflected magnitude were similar at all time points. FMD and baseline diameter remained similar. These data indicate preservation of macrovascular (endothelial) function, but not microvascular function resulting from the 50 km ultramarathon.

The association between smoking exposure and endothelial function evaluated using flow-mediated dilation values: a meta-analysis.

BACKGROUND: Tobacco use is recognized as a major cause of cardiovascular disease, which is associated with endothelial dysfunction. Endothelial function is evaluated using flow-mediated dilation (FMD), which is a noninvasive method. This meta-analysis aimed to investigate the association between smoking exposure and endothelial function evaluated using FMD values. METHODS: We searched the PubMed, Embase, Web of Science, and Cochrane Library databases for cohort studies of smokers or passive smokers that used FMD to assess endothelial function. The primary outcome of the study was the change in the rate of FMD. The risk of bias was evaluated using the Cochrane Collaboration tool and Newcastle-Ottawa Scale. Further, the weighted mean difference was used to analyze the continuous data. RESULTS: Overall, 14 of 1426 articles were included in this study. The results of these articles indicated that smoking is a major cause of endothelial dysfunction and altered FMD; a pooled effect size of - 3.15 was obtained with a 95% confidence interval of (- 3.84, - 2.46). Notably, pregnancy status, Asian ethnicity, or health status did not affect heterogeneity. CONCLUSIONS: We found that smoking has a significant negative impact on FMD, and measures such as medication or education for smoking cessation may improve endothelial function and reduce the risk of cardiovascular disease. TRIAL REGISTRATION: The meta-analysis was registered with PROSPERO on April 5th, 2023 (CRD42023414654).

Antioxidant therapies for obstructive sleep apnea: A systematic review and meta-analysis.

PURPOSE: Obstructive sleep apnea (OSA) is a common clinical problem that is associated with adverse cardiovascular outcomes attributed to the oxidative stress due to sympathetic overstimulation. Treatment approaches targeting oxidative stress have been tried by multiple investigators. This systematic review and meta-analysis evaluated the efficacy and safety of such approaches. METHODS: Pubmed and Embase databases were searched for human studies evaluating the utility of antioxidant therapies in patients with OSA. RESULTS: A total of six studies (five randomized trials and one case-control study) were included, including 160 patients with OSA using N-acetyl cysteine, vitamin C, carbocysteine, superoxide dismutase, vitamin E, allopurinol, and their combinations. There was a significant improvement in flow-mediated dilatation (FMD) following antioxidants, with the pooled effect being 2.16 % (95% CI 1.65-2.67) using the random-effects model (I2 = 0% and p<0.001). It was also associated with a significant reduction in malondialdehyde levels and an increase in reduced glutathione (GSH) levels. There was also a significant improvement in the Epworth sleepiness scale, oxygen desaturation index, and minimum oxygen saturation during sleep without any significant adverse effects. CONCLUSION: Antioxidant therapy in patients with OSA is associated with improved endothelial function, reduced oxidative stress, and improved sleep parameters. These results call for future multicentre studies with longer follow-ups to assess the utility of antioxidant therapy in patients with OSA.

Deletion of Sigmar1 leads to increased arterial stiffness and altered mitochondrial respiration resulting in vascular dysfunction.

Sigmar1 is a ubiquitously expressed, multifunctional protein known for its cardioprotective roles in cardiovascular diseases. While accumulating evidence indicate a critical role of Sigmar1 in cardiac biology, its physiological function in the vasculature remains unknown. In this study, we characterized the expression of Sigmar1 in the vascular wall and assessed its physiological function in the vascular system using global Sigmar1 knockout (Sigmar1-/-) mice. We determined the expression of Sigmar1 in the vascular tissue using immunostaining and biochemical experiments in both human and mouse blood vessels. Deletion of Sigmar1 globally in mice (Sigmar1-/-) led to blood vessel wall reorganizations characterized by nuclei disarray of vascular smooth muscle cells, altered organizations of elastic lamina, and higher collagen fibers deposition in and around the arteries compared to wildtype littermate controls (Wt). Vascular function was assessed in mice using non-invasive time-transit method of aortic stiffness measurement and flow-mediated dilation (FMD) of the left femoral artery. Sigmar1-/- mice showed a notable increase in arterial stiffness in the abdominal aorta and failed to increase the vessel diameter in response to reactive-hyperemia compared to Wt. This was consistent with reduced plasma and tissue nitric-oxide bioavailability (NOx) and decreased phosphorylation of endothelial nitric oxide synthase (eNOS) in the aorta of Sigmar1-/- mice. Ultrastructural analysis by transmission electron microscopy (TEM) of aorta sections showed accumulation of elongated shaped mitochondria in both vascular smooth muscle and endothelial cells of Sigmar1-/- mice. In accordance, decreased mitochondrial respirometry parameters were found in ex-vivo aortic rings from Sigmar1 deficient mice compared to Wt controls. These data indicate a potential role of Sigmar1 in maintaining vascular homeostasis.

Endothelial Function in Pulmonary Arterial Hypertension: From Bench to Bedside.

Pulmonary arterial hypertension is a complex pathology whose etiology is still not completely well clarified. The pathogenesis of pulmonary arterial hypertension involves different molecular mechanisms, with endothelial dysfunction playing a central role in disease progression. Both individual genetic predispositions and environmental factors seem to contribute to its onset. To further understand the complex relationship between endothelial and pulmonary hypertension and try to contribute to the development of future therapies, we report a comprehensive and updated review on endothelial function in pulmonary arterial hypertension.

Relationship of Warfarin and Apixaban with Vascular Function in Patients with Atrial Fibrillation.

INTRODUCTION: Atrial fibrillation (AF) is associated with endothelial damage/dysfunction. Herein, we tested the hypothesis that brachial artery flow-mediated dilation (FMD) is superior in AF patients taking apixaban compared to warfarin. METHODS: AF patients on apixaban (n = 46; 67 [7] years; mean [standard deviation]; 15 women) and warfarin (n = 27; 73 [9] years (p < 0.01); 11 women) were recruited. Duplex Doppler ultrasound imaging was undertaken during baseline (2 min), cuff inflation (5 min), and following cuff deflation (3 min). FMD was defined as peak increase in brachial artery diameter following cuff deflation and analysed as percentage change in diameter, as a ratio of FMD, shear rate area under the curve (SRAUC; FMD-to-SRAUC), and using SRAUC as a covariate (FMDSR). RESULTS: Baseline artery diameter (4.96 [1.14] vs. 4.89 [0.88] mm), peak diameter (5.12 [1.17] vs. 5.14 [0.93] mm), and FMDSR (3.89 [3.62] vs. 4.80 [3.60] %) were not different between warfarin and apixaban (p > 0.05; analysis of covariance with age, CHA2DS2-VASc, years since AF diagnosis, number of diabetics, alcohol drinkers, and units of alcohol consumed per week as covariates). Stepwise multiple regression identified independent association of fibrillation, hypertension, and increased age with FMD. CONCLUSION: AF patients on warfarin and apixaban exhibit similar endothelium-dependent vasodilation. Increased blood pressure negatively impacts vasodilator capacity in AF patients.

Augmented mannose-binding lectin levels in primary membranous nephropathy: A pilot study.

There is evidence to suggest that M-type phospholipase A2 (PLA2R) antibodies activate the mannose-binding lectin (MBL) cascade, resulting in glomerular damage and proteinuria in patients with primary membranous nephropathy (PMN). Furthermore, there are few reports indicating that aberrant MBL activation is associated with endothelial dysfunction and accelerated atherosclerosis. While PMN is a common cause of adult nephrotic syndrome, and patients are at increased risk of cardiovascular disease (CVD), there is a lack of research that explores the factors that contribute to this condition. This study aims to determine the MBL levels in PMN and their relation to the clinical activity and endothelial dysfunction in PMN. The MBL levels of 22 biopsy-confirmed PMN patients were assessed at baseline and after 6 months of immunosuppressive therapy. In order to evaluate endothelial dysfunction in PMN patients, flow-mediated vasodilation (FMD) was measured at baseline and after treatment. A total of 22 healthy controls were included in this study to measure MBL levels and FMD. A significant difference was observed between MBL levels in PMN patients and healthy controls (p < .01). MBL levels decreased significantly after immunosuppressive therapy (p = .04). The baseline MBL levels and FMD levels exhibited a strong correlation (Spearman correlation coefficient [ρ] = 0.51: p = .01). In conclusion, the study signals the activation of the MBL cascade and its association with endothelial dysfunction in PMN patients.

Effects of pre-exercise intake of plant- and animal-based foods on arterial function and aerobic exercise capacity in healthy young men: a randomized cross-over trial.

The purpose of this study was to examine the effects of plant- versus animal-based food intake before exercise on arterial function and subsequent aerobic exercise capacity. Eleven healthy adult males (mean age, 22.6 ± 1.8 years) participated in this study. A plant- or animal-based randomized meal type crossover comparison was conducted on separate days with a uniform protein, fat, and carbohydrate balance. Both carotid-femoral pulse wave velocity (cfPWV), femoral-ankle pulse wave velocity (faPWV), and brachial artery flow-mediated dilatation (FMD) were measured as indexes of aortic and peripheral arterial stiffness and vascular endothelial function, respectively, before and at 120 min after the meal. After these measurements, maximal oxygen uptake was assessed using a graded power test on an electronically braked cycle ergometer. The results revealed that cfPWV was significantly lower, whereas FMD was significantly higher, at 120 min after compared with before the plant-based meal (p = 0.01 and 0.02, respectively). By contrast, cfPWV and FMD did not change at 120 min after compared with before the animal-based meal. In addition, faPWV did not change at 120 min after compared with before the meal for either meal type. Maximal oxygen uptake was higher in the plant- than in the animal-based meal type (p = 0.02). These results suggest that pre-exercise plant-based food intake may improve central arterial stiffness and vascular endothelial function, which may have favorable implications for aerobic exercise capacity.

Insulin pump treatment vs. multiple daily insulin injections in patients with poorly controlled Type 2 diabetes mellitus: a comparison of cardiovascular effects.

AIMS: Both hyperglycaemia and large glycaemic variability are associated with worse outcomes in patients with Type 2 diabetes mellitus (T2DM), possibly causing sympatho-vagal imbalance and endothelial dysfunction. Continuous subcutaneous insulin injection (CSII) improves glycemic control compared to multiple daily insulin injections (MDI). We aimed to assess whether CSII may improve cardiac autonomic and vascular dilation function compared to MDI. METHODS: We enrolled T2DM patients without cardiovascular disease with poor glycaemic control, despite optimized MDI therapy. Patients were randomized to continue MDI (with multiple daily peripheral glucose measurements) or CSII; insulin dose was adjusted to achieve optimal target ranges of blood glucose levels. Patients were studied at baseline and after 6 months by: 1) flow-mediated dilation (FMD) and nitrate-mediated dilation (NMD) of the brachial artery; 2) heart rate variability (HRV) by 24-hour ECG Holter monitoring (HM). 7-day continuous glucose monitoring (CGM) was performed in 9 and 8 patients of Group 1 and 2, respectively. RESULTS: Overall, 21 patients were enrolled, 12 randomized to CSII (Group 1) and 9 to MDI (Group 2). The daily dose of insulin and Hb1AC did not differ significantly between the 2 groups, both at baseline and at follow-up. Glucose variability showed some significant improvement at follow-up in the whole population, but no differences were observed between the 2 groups. Both FMD and NMD, as well as HRV parameters, showed no significant differences between the 2 groups at 6-month follow-up. CONCLUSIONS: In this randomized small study we show that, in T2DM patients, CSII achieves a similar medium-term glycemic control compared to MDI, without any adverse effect on the cardiovascular system.

Influence of physical activity on endothelial function in people living with HIV.

INTRODUCTION: Decreased physical activity is a major cardiovascular risk factor that is particularly pronounced in people living with HIV (PLHIV), who are more susceptible to endothelial dysfunction and accelerated atherosclerosis than the general population due to multiple mechanisms. The aim of the present study was to analyse whether regular physical activity is capable of improving endothelial function measured by flow-mediated dilatation (FMD) in PLHIV. METHODS: We performed FMD measurement in 38 PLHIV, along with the assessment of their regular physical activity level using the International Physical Activity Questionnaire (IPAQ). RESULTS: Flow-mediated dilatation results in PLHIV were 0.31 ± 0.06 mm and 7.34% ± 1.41% for absolute and relative FMD, respectively. IPAQ results showed that the average weekly level of physical activity was 3631.1 ± 1526.7 MET-min/week, whereas the average daily sitting time was 287.3 ± 102.7 min/day. Predictors jointly accounted for 48% (adjusted value 42%) of FMD variance. Bootstrapped confidence levels revealed that physical activity had a statistically significant effect on the outcome [beta = 0.517, 2.5% confidence interval (CI) = 0.205, 97.5% CI = 0.752]. CONCLUSION: Physical activity represents a widely available and uncostly tool that is capable of improving endothelial function and overall cardiovascular health in PLHIV.

Effect of Yoga on Endothelial Function: A Systematic Review and Meta-Analysis.

Introduction: Endothelial dysfunction is the initial step in the pathogenesis of atherosclerosis; and it plays a central role in the development of cardiovascular diseases and many types of human diseases (diabetes, kidney failure, cancer, and viral infections). Strategies that are effective in protecting vascular endothelial function and retard or reversing endothelial dysfunction in the early stage appear to be potential in the prevention of vascular, cardiac, and many human diseases. Several studies have been carried out on the effects of yoga on endothelial function, but the results of these studies have not been synthesized. This study aimed at conducting a systematic review and meta-analysis to determine the effectiveness of yoga on endothelial function. Methods: A systematic review and meta-analysis of studies that assessed the effect of yoga practice on vascular endothelial function was done as per the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The PubMed, Scopus, Google Scholar, and Cochrane controlled register of trials (CENTRAL) were searched from inception to August 2022. The search strategy was constructed around yoga-based techniques and endothelial function. All the yoga-based interventional studies on endothelial function or dysfunction were included in this review. A narrative synthesis and descriptive analysis were done due to the diverse methodology of selected studies. We carried out a formal meta-analysis of controlled trials that assessed the effect of yoga on flow-mediated dilatation (FMD), a measure of endothelial function. Results: A total of 18 studies were included for review involving 1043 participants. Yoga training showed improved endothelial function in 12 studies, whereas 6 studies did not find any statistically robust effect. Meta-analysis (n = 395 participants, 6-studies, 7 comparisons) showed an increase in brachial FMD by yoga practice (mean difference = -1.23%; 95% confidence interval -2.23 to -0.23; p = 0.02). The heterogeneity between the studies was 43% (Tau2 = 0.70, χ2 = 10.49). The risk of bias was low to moderate in these studies. No adverse effects were reported. Conclusions: Yoga practice improved endothelial function. Yoga could be a safe and potential integrative medicine to improve endothelial function. However, as the statistical heterogeneity, that is, variation in the FMD among the studies was moderate, large clinical trials are necessary for its clinical recommendations.

Impaired retinal micro-vascular function in patients with atrial fibrillation.

BACKGROUND: Cardiovascular (CV) risk factors and CV diseases, in particular heart failure, are strongly associated with impaired microvascular retinal endothelial function. Whether atrial fibrillation (AF) contributes to vascular dysfunction is not clear. Therefore, the aim of this study was to investigate the impact of AF on retinal microvascular function. METHODS: In this study, vascular function was measured non-invasively with flicker-light induced vasodilatation of retinal arterioles (FIDart%). Patients with a history of AF and risk factors for heart failure (HF) or heart failure (n = 69; age 67.9 ± 9.2 years, 71% male, 35% HFrEF, 56% paroxysmal, 25% persistent, 19% permanent AF), as well as age, sex and ejection fraction matched patients with absent history of AF (n = 66; age 63.4 ± 10.6 years, 67% male, 47% HFrEF) were included. Patients with AF were further divided into those with paroxysmal AF (in sinus rhythm - AFSR: n = 38, age 71.4 ± 9.2, 73% male), and those with AF at the time of the study visit. RESULTS: Retinal microvascular function was impaired in patients with AF compared to patients without AF (FIDart% 1.1% [0.3-2.8] vs. 2.7% [1.3-5.1], p < 0.001). Patients currently in AF have poorer retinal microvascular function (FIDart% 0.8% [0.1-1.9) compared to patients with a history of AF but currently in SR at the time of retinal function measurement (1.5% [0.6-4.9] p = 0.017). In patients with AF, impaired retinal vascular function was independently associated with larger left atrial volume (mean 49.8 ± 18.4), even after correction for confounding factors in different models (SCR = -0. 251 to -0.256, p = 0.035-0.01). CONCLUSIONS: AF in patients with heart failure is associated with impaired vascular function, even if currently in sinus rhythm. The association of retinal microvascular dysfunction with left atrial volume, a surrogate for elevated cardiac filling pressures, may further highlight the important interplay between the vasculature and elevated filling pressures in the development of AF.

Impact of irregular sleep pattern, and sleep quality on glycaemic parameters and endothelial function in adolescents and young adults with type 1 diabetes.

This study investigated the impact of comprehensive sleep patterns on glycaemic parameters and endothelial function in adolescents and young adults with type 1 diabetes (T1D). Thirty subjects with type 1 diabetes (aged 13-25) without chronic complications participated. For 1 week, glucose levels were monitored by real-time continuous glucose monitoring (CGM) and sleep was simultaneously assessed by actigraphy. Subjective sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). Flow-mediated dilatation (FMD) measured endothelial function at the brachial artery. Insulin sensitivity was determined by calculated estimated glucose disposal rate (eGDR). Glycaemic control was assessed using haemoglobin A1C (HbA1C) levels. To address potential confounding by metabolic syndrome on the FMD results, three affected subjects were excluded from FMD correlation analyses. Participants with PSQI scores >5 had a lower %FMD compared with those with scores ≤5 (4.6 ± 3.7% vs. 7.6 ± 3.0%, p = 0.03). Multivariate analysis indicated that lower sleep efficiency and higher sleep duration variability were associated with higher HbA1C levels (ß = -0.076, 95%CI [-0.145, -0.008], p = 0.029; ß = 0.012, 95%CI [0.001, 0.023], p = 0.033). Irregular sleep timing and lower sleep efficiency were related to decreased insulin sensitivity (sleep midpoint irregularity ß = -1.581, 95%CI [-2.661, -0.502], p = 0.004, and sleep efficiency ß = 0.147, 95%CI [0.060, 0.235], p = 0.001). No significant associations were found between glycaemic parameters and FMD. Our study demonstrated that sleep irregularity in type 1 diabetes was associated with glycaemic control and insulin resistance, while poor subjective sleep quality was linked to endothelial dysfunction. Promoting healthy sleep habits, including consistent sleep timing could benefit metabolic and cardiovascular health in type 1 diabetes.

Fat intake impairs the recovery of endothelial function following mental stress in young healthy adults.

Introduction: Mental stress has been identified as a trigger of cardiovascular events. A single episode of stress can induce acute impairments in endothelial function in healthy adults. Importantly, during stressful periods, individuals often resort to unhealthy behaviors, such as increased consumption of high-fat foods, which is also known to negatively impact endothelial function. Therefore, this study examined whether consumption of a high-fat meal would further exacerbate the negative effect of mental stress on vascular function. Methods: In a randomized, counterbalanced, cross- over, postprandial intervention study, 21 healthy males and females ingested a high-fat (56.5 g fat) or a low-fat (11.4 g fat) meal 1.5 h before an 8-min mental stress task (Paced-Auditory-Serial-Addition-Task, PASAT). Plasma triglyceride (TAG) concentration was assessed pre-and post-meal. Forearm blood flow (FBF), blood pressure (BP), and cardiovascular activity were assessed pre-meal at rest and post-meal at rest and during stress. Endothelial function, measured by brachial flow-mediated dilatation (FMD) was assessed pre-meal and 30 and 90 min following mental stress. Results: Plasma TAG concentration was significantly increased following the high-fat meal compared to the low-fat condition. Mental stress induced similar increases in peripheral vasodilation, BP, and cardiovascular activity, and impaired FMD 30 min post-stress, in both conditions. FMD remained significantly impaired 90 min following stress in the high-fat condition only, suggesting that consumption of fat attenuates the recovery of endothelial function following mental stress. Discussion: Given the prevalence of fat consumption during stressful periods among young adults, these findings have important implications for dietary choices to protect the vasculature during periods of stress.

A case-control study of early-stage radiological markers of endothelial dysfunction and cardiovascular findings in patients with osteogenesis imperfecta: genotype-phenotype correlations.

OBJECTIVES: Osteogenesis imperfecta (OI) is a disease caused by defective collagen synthesis. Collagen type 1 is found in many structures in the cardiovascular system. Endothelial dysfunction, which develops prior to the emergence of structural and clinical signs of atherosclerosis, is believed to play a key role in atherogenesis. Endothelial dysfunction may be detected presymptomatically by non-invasive radiologic methods, such as flow-mediated dilatation (FMD) and carotid intima-media thickness (CIMT). These modalities may provide early indicators of endothelial dysfunction. This cross-sectional comparative study aimed to investigate early-stage radiological markers of endothelial dysfunction and cardiovascular diseases in OI patients and healthy controls and to investigate the correlation of findings with OI genotype. METHODS: Thirty patients diagnosed with OI were paired with thirty healthy age- and gender-matched controls and echocardiogram findings were compared. RESULTS: None of the patients had known underlying cardiovascular disease. The mean age was 13.18 ± 2.91 years. According to Sillence classification, 15 patients had type 1 OI, 10 had type III, and 5 had type IV. Mean CIMT in the OI group was higher in the control group (OI group: 0.42 ± 0.06 vs. healthy controls: 0.34 ± 0.04 mm, p<0.01), and mean FMD percent was lower in the patient group (p<0.01). Left ventricular ejection fraction was 78.97 ± 10.32 vs. 77.56 ± 8.50 %, (OI group: 7.00 ± 3.06 vs. healthy controls: 12.14 ± 1.99, p=0.56), and fractional shortening was 42.68 ± 11.94 vs. 40.23 ± 7.99 %, (p=0.35), in OI patients and controls, respectively. CONCLUSIONS: Pediatric patients with OI without clinical signs of cardiovascular abnormality had significantly worse CIMT and FMD findings than healthy controls. However, no difference was determined when comparing left ventricular ejection fraction or fractional shortening. OI patients may need to be screened for cardiovascular system complications starting from an early age.

Association of plasma xanthine oxidoreductase activity with vascular endothelial function independent of serum uric acid level: MedCity21 health examination registry.

Background: Xanthine oxidoreductase (XOR) inhibitor administration, known to reduce uric acid and reactive oxygen species (ROS) production, also improves vascular endothelial function (VEF). This cross-sectional study examined our hypothesis that XOR contributes to impaired VEF through ROS but not uric acid production. Methods: In 395 subjects (196 males, 199 females) without urate-lowering agent administration who underwent a health examination, plasma XOR activity was determined using our highly sensitive assay based on [13C2,15N2] xanthine and liquid chromatography/triple quadrupole mass spectrometry. For VEF evaluation, flow-mediated dilatation (FMD) in the brachial artery was determined by ultrasound, with physical and laboratory measurements also obtained. Results: The median values for plasma XOR activity, serum uric acid, and FMD were 26.6 pmol/h/mL, 5.4 mg/dL, and 6.2%, respectively. Simple regression analysis showed weak correlations of both log plasma XOR activity and serum uric acid level with FMD (r = -0.213, p < 0.001 and r = -0.139, p = 0.006, respectively). However, multivariable linear regression analyses revealed that log plasma XOR activity but not serum uric acid level remained associated with FMD (ß = -0.116, p = 0.037 and ß = 0.041, p = 0.549, respectively) after adjustments for various clinical parameters, with no remarkable inconsistencies for the association observed in subgroups divided based on sex or uric acid level. Finally, a series of mediation analyses showed that serum uric acid level did not meet the criteria for mediator of the association of plasma XOR activity with FMD (p = 0.538). Conclusions: These findings suggest the possibility that XOR contributes to the pathophysiology of impaired VEF through ROS but not uric acid production.

Diverging role of epicardial adipose tissue across the entire heart failure spectrum.

AIMS: Epicardial adipose tissue (EAT) is a metabolically highly active tissue modulating numerous pathophysiological processes. The aim of this study was to investigate the association between EAT thickness and endothelial function in patients with heart failure (HF) across the entire ejection fraction spectrum. METHODS AND RESULTS: A total of 258 patients with HF with an ejection fraction across the entire spectrum [HF with reduced ejection fraction (HFrEF), n = 168, age 60.6 ± 11.2 years; HF with preserved ejection fraction (HFpEF), n = 50, mean age 65.1 ± 11.9 years; HF with mildly reduced ejection fraction (HFmrEF), n = 32, mean age 65 ± 12] were included. EAT was measured with transthoracic echocardiography. Vascular function was assessed with flicker-light-induced vasodilation of retinal arterioles (FIDart%) and flow-mediated dilatation (FMD%) in conduit arteries. Patients with HFrEF have less EAT compared with patients with HFpEF (4.2 ± 2 vs. 5.3 ± 2 mm, respectively, P < 0.001). Interestingly, EAT was significantly associated with impaired microvascular function (FIDart%; r = -0.213, P = 0.012) and FMD% (r = -0.186, P = 0.022), even after multivariate correction for confounding factors (age, body mass index, hypertension, and diabetes; standardized regression coefficient (SRC) = -0.184, P = 0.049 for FIDart% and SRC = -0.178, P = 0.043 for FMD%) in HFrEF but not in HFpEF. CONCLUSIONS: Although less EAT is present in HFrEF than in HFpEF, only in HFrEF EAT is associated with vascular dysfunction. The diverging role of EAT in HF and its switch to a functionally deleterious tissue promoting HF progression provide the rationale to specifically target EAT, in particular in patients with reduced ejection fraction.