Flow-mediated Dilation Research Articles

Dietary Protein in a Challenge Meal Does Not Alleviate Postprandial Impairments in Vascular Endothelial Function in Healthy Older Adults with Cardiometabolic Risk: A Randomized Crossover-Controlled Trial

BackgroundPostprandial vascular endothelial dysfunction is an early marker of atherosclerosis. Meal protein has been reported to reduce endothelial dysfunction in adults, and the effect could be mediated by the amino acid content. ObjectivesThis trial aims to assess the effect of a specifically designed plant-protein blend that contains high leucine, arginine, and cysteine on postprandial endothelial function in the elderly. MethodsIn a randomized, double-blind, 3-period crossover (2-wk washout), controlled trial, we compared the vascular effects of 3 high-saturated-fat high-sucrose (HFHS) meals based on either our specific plant-protein blend, milk protein, or without added protein. The trial was conducted on 29 healthy adults aged >65 y presenting ≥2 cardiometabolic risk factors. Postprandial vascular function was evaluated at fasting, 3 h, and 5 h postprandially, using brachial flow-mediated dilation (FMD), hand microvascular reactivity (using Flowmetry Laser Doppler, FLD), and finger reactive hyperemia index (using Peripheral Arterial Tonometry, RHI). Immune cell count and gene expression in peripheral blood mononuclear cells (PBMCs) were also assessed postprandially. Data were analyzed using mixed linear models with repeated measurements on participants for meal composition and time of sampling. This trial was registered at clinicaltrials.gov as NCT04923555. ResultsFMD incremental AUC value decreased after meals (time effect P < 0.01), with no significant differences between meals. RHI also decreased with time (P < 0.01). PBMC count and monocyte chemoattractant protein-1, IL-1b, and IL-6 expression increased after meals showing postprandial endothelial activation (P < 0.05). Overall, meal composition had no effect on any of the postprandial changes (Ps>0.10). ConclusionsIn healthy adults aged >65 y presenting cardiometabolic risk, adding protein to an HFHS challenge meal does not mitigate postprandial impairments in vascular endothelial function and inflammatory activation. Further studies are needed to explore the potential differences with younger adults.

VascuFit: Aerobic exercise improves endothelial function independent of cardiovascular risk: A randomized-controlled trial.

Background and aimsEndothelial dysfunction predicts elevated cardiovascular (CV) risk in healthy individuals. Aerobic exercise reduces endothelial dysfunction in part by improving CV risk factors. Yet, this explains less than 50% of the effect and a direct influence of exercise training on the endothelium is discussed as possible contributor. The VascuFit study applied non-linear periodized aerobic exercise (NLPE) training to assess its multilevel effects on endothelial function including potential epigenetic endothelial modifications by circulating micro-ribonucleic acids (endomiRs). MethodsSedentary adults with elevated CV risk between 40-60 years were randomized 2:1 and engaged in an eight-week ergometer-based NLPE training (n=30) or received standard exercise recommendations (n=14). Macro-, microvascular, cellular and molecular adaptations were assessed via brachial-arterial flow-mediated dilation (baFMD), static retinal vessel analysis (SVA), flow cytometry, and endomiRs regulating key pathways of endothelial function. Statistics included ANCOVA, Principal Component Analysis (PCA), and regression analyses. ResultsbaFMD improved by 2.38% (CI:0.70-4.06, p=0.007) independent of CV risk, whereas SVA parameters and circulating endothelial (progenitor) cells did not significantly change in the NLPE group. The mean distance between baseline and follow-up PCA loadings of the endomiR dataset explaining 44.2% of dataset variability was higher in the NLPE-group compared to the control group (2.71±2.02 vs. 1.65±0.93). However, regression analyses showed no evidence of endomiRs explaining the improvement of baFMD. ConclusionsThe improvement of macrovascular endothelial function by aerobic exercise training was independent from CV risk factors. Increased heterogeneity among endomiRs did not explain this effect, but suggests an adaptive response to the exercise stimulus on the epigenetic level.

The relationship between exercise-related hypertension and carotid artery intima media thickness and brachial artery endothelial function

Aims: Hypertension is one of the most common chronic diseases in the world. There are some non-invasive tests which are used to assess end organ damages in patients with hypertension. The purpose of this study is to show relationship between carotid artery intima media thickness (CIMT) and flow mediated dilatation (FMD) in patients with exercise induced hypertension (EIH). Methods: 73 healthy normotensive men and women, who are between 18 and 65 years of age, participated in this study. All patients underwent electrocardiography, echocardiography, 24-hour ambulatory blood pressure monitoring and symptom-limited treadmill testing before CIMT and FMD were measured with Doppler ultrasonography. CIMT and FMD values of both groups were statistically compared with each other. Results: Of a total of 73 individuals, 56 were evaluated as the patient group and 17 as the control group. Age, smoking rate, body mass index, resting and maximum blood pressure values, and ascending aorta diameter were significantly higher in the patient group (p=0.02 for smoking, p&lt;0.01 for the rest). Right/left main CIMT, right/left bulbus IMT, and left ventricular diastolic dysfunction was significantly higher in the patient group (p&lt;0.05 for all). In addition, the mean CIMT and mean FMD (%) values were significantly higher and lower, respectively, in the patient group compared to the control group. No difference was observed between the two groups in terms of right/left internal CIMT and passive smoking exposure. In addition, the mean values of CIMT and FMD (%) did not show a statistically significant difference according to hypertensive response stages and gender. Conclusion: CIMT and FMD are significantly associated with EIH. EIH should be evaluated as important risk factor for future hypertension and may cause asymptomatic end-organ damage. It can be easily assessed using CIMT and FMD.

Vascular Pathogenesis in Acute and Long COVID: Current Insights and Therapeutic Outlook.

Long coronavirus disease 2019 (COVID-19)-a postacute consequence of severe acute respiratory syndrome coronavirus 2 infection-manifests with a broad spectrum of relapsing and remitting or persistent symptoms as well as varied levels of organ damage, which may be asymptomatic or present as acute events such as heart attacks or strokes and recurrent infections, hinting at complex underlying pathogenic mechanisms. Central to these symptoms is vascular dysfunction rooted in thrombotic endothelialitis. We review the scientific evidence that widespread endothelial dysfunction (ED) leads to chronic symptomatology. We briefly examine the molecular pathways contributing to endothelial pathology and provide a detailed analysis of how these cellular processes underpin the clinical picture. Noninvasive diagnostic techniques, such as flow-mediated dilation and peripheral arterial tonometry, are evaluated for their utility in identifying ED. We then explore mechanistic, cellular-targeted therapeutic interventions for their potential in treating ED. Overall, we emphasize the critical role of cellular health in managing Long COVID and highlight the need for early intervention to prevent long-term vascular and cellular dysfunction.

Pulse transmission time and amplitude of digital pulse wave determined by fingertip plethysmography as a surrogate marker of brachial artery flowmediated dilatation.

To assess the changes in blood vessel stiffness and digital pulse wave amplitude because of flowmediated dilatation, and to explore how these two variables change when endothelial dysfunction is experimentally induced. The experimental study was conducted at the departments of physiology at the College of Medicine, Mustansiriyah University, and the College of Medicine, Al-Iraqia University, Baghdad, Iraq, from October 14, 2021, to May 31, 2022, and comprised healthy young males who were subjected to the flow-mediated dilatation technique on the left brachial artery. Pulse transit time and the amplitude of the digital pulse wave were measured during reactive hyperaemia for 2.5 minutes from the left middle finger using a piezoelectric pressure sensor and a simultaneous Lead I electrocardiogram. Endothelial dysfunction (ED) was induced by oscillatory and retrograde shear rates. The correlation between variables was calculated in Excel running on the Windows operating system. There were 10 second-year medical students with mean age 22±0 years and mean body mass index 25.7±4.8kg/m2. During reactive hyperaemia, pulse transit time was significantly increased by 3-5% in both normal endothelium and experimentally induced endothelial dysfunction relative to the pre-occluded artery, and the difference was not significant (p>0.05). Digital pulse wave amplitude increased significantly in normal endothelium relative to the pre-occluded artery (p<0.05), but not in experimentally-induced endothelial dysfunction (p>0.05). The pulse transit time and digital pulse wave amplitudes of the photo plethysmography signal may be used to detect changes in vessel wall diameter and tone throughout the reactive hyperaemia process. Digital pulse wave amplitude was better able to detect experimentally-induced endothelial dysfunction, as assessed by the flowmediated dilatation protocol, than pulse transit time.

Exploring the Impact of Inhaled Corticosteroids on Endothelial Function in Chronic Obstructive Pulmonary Disease Patients Undergoing Pulmonary Rehabilitation.

Background: Chronic obstructive pulmonary disease (COPD) is associated with subclinical atherosclerosis and endothelial dysfunction, which can be assessed non-invasively through flow-mediated dilation (FMD). In this study, we evaluated the potential impact of inhaled corticosteroid (ICS) therapy on FMD of COPD patients undergoing pulmonary rehabilitation (PR). Methods: Medical records of COPD patients undergoing FMD assessment upon admission to our Pulmonary Rehabilitation Unit were reviewed in this retrospective post hoc analysis. Results: A total of 46 patients with COPD (median age 71.5 years, 28.3% postmenopausal females) were included in the final analysis. Among these, 27 participants were currently receiving ICS therapy, while 19 were not. At baseline, the two groups showed no difference in the main clinical and functional variables. Similarly, no significant difference was observed in vascular reactivity parameters, with a median FMD of 3.12% (IQR: 2.23-4.45) in ICS users and 3.39% (IQR: 2.45-4.08) in ICS nonusers (p = 0.544). After PR, a significant improvement in the main rehabilitation and patient-reported outcomes was observed in all groups, with a significant improvement in FMD documented in both patients treated with steroids (from 3.12%; IQR: 2.23-4.45 to 4.77%; IQR: 3.25-5.63, p = 0.022) and in those who were not (from 3.39%; IQR: 2.45-4.08 to 5.04%; IQR: 3.98-6.06, p = 0.005). FMD changes were of comparable magnitude among groups. Conclusions: Our preliminary findings do not indicate a significant impact of medications containing ICS on the endothelial function of COPD patients, suggesting that the potential beneficial effect of PR on this surrogate marker of cardiovascular risk is independent of inhaled therapy.

Micro- and macrovascular function in the highest city in the world: a cross sectional study

Since vascular responses to hypoxia in both healthy high-altitude natives and chronic mountain sickness (a maladaptive high-altitude pathology characterised by excessive erythrocytosis and the presence of symptoms-CMS) remain unclear, the role of inflammation and oxidative/nitrosative stress on the endothelium-dependent and -independent responses in both the micro- and macrocirculation, in healthy Andeans at different altitudes and in CMS patients, was examined. 94 men were included: 18 lowlanders (LL), 38 healthy highlanders permanently living at 3800m (n=21-HL-3800) or in La Rinconada, the highest city in the world (5100-5300m) (n=17-HL-5100/No CMS). Moreover, 14 participants with mild (Mild CMS) and 24 with moderate to severe CMS (Mod/Sev CMS) were recruited. All undertook two reactivity tests: i) local thermal hyperaemia (microcirculation) and ii) flow-mediated dilation (macrocirculation). Endothelium-independent function (glyceryl trinitrate) was also assessed only in La Rinconada. Conductance and skin blood flow velocity during the microcirculation test, as well as macrocirculation progressively decreased with altitude (LL>HL-3800 > HL-5100/No CMS). CMS also induced a decrease in macrocirculation (HL-5100/No CMS>Mild CMS= Mod/Sev CMS), while glyceryl trinitrate restored vascular function. Both oxidative stress and nitric oxide metabolites increased with altitude only. Principal component analysis revealed that increasing inflammation with altitude was associated with a progressive decline in both micro- and macrovascular function in healthy highlanders. Both micro and macrovascular function are affected by chronic exposure to hypoxia, the latter being further compounded by CMS. The "Fonds de dotation AGIR pour les maladies chroniques", the "Air Liquide Foundation", and the "French National Research Agency".

The effect of periodontal treatments on endothelial function in degrees of periodontitis patients: A systematic review and meta-analysis.

This article focus on patients with moderate-to-severe periodontitis and periodontitis patients with cardiovascular disease. After they received periodontal initial therapy or antimicrobial drug treatment, was there any improvement in endothelial function during short- and long-term followups? Relevant randomized controlled trials and clinical trials up to 30th June 2024 were identified and retrieved from electronic databases including PubMed, Cochrane Library, Web of Science and CNKI databases, with periodontitis therapy, periodontal disease and endothelial function as the keywords. The weighted (WMD) or standardized mean difference (SMD) was calculated using a fixed- or random-effect model and assessed heterogeneous results. Generally, 14 studies published between 2004 and 2022 were eligible for the meta-analysis, which are all randomised clinical trials. A total of 491 periodontitis patients were screened. All participants received whole-mouth supragingival and subgingival scaling and root planing of the teeth, some trials combined with antimicrobial drug treatment as well as extracting teeth that could not be saved. The outcome indicators were measured by flow-mediated dilatation(FMD) levels. The results of the short term (≤3 months) periodontitis initial therapy group showed positive results (WMD = -3.78,95%CI = [-5.49,-2.07], P<0.0001), while the results of the long term (6 months) periodontitis therapy group exhibited significant difference (WMD = -0.96,95%CI = [-2.06,0.14],P = 0.09). Furthermore, study population were categorized according to the severity of periodontitis, the presence of comorbidities, endothelial dysfunction, and the inclusion of extractions and antimicrobial therapy in the treatment process. The effects of each of these factors on FMD were explored and the results of these subgroups all support periodontitis therapy. The results showed that periodontal treatment enhances endothelial function. Additionally, after subgroup analysis of long-term and short-term follow-up, patients with severe periodontitis, and different periodontal treatments, periodontal therapy was shown to increase FMD levels.

Breakfast skipping suppresses the vascular endothelial function of the brachial artery after lunch.

Breakfast skipping has been suggested to be associated with cardiovascular diseases. However, whether breakfast skipping affects vascular endothelial function (VEF), a marker of cardiovascular diseases, remains unclear. This study aimed to investigate the impact of breakfast consumption (Eating trial) and skipping (Skipping trial) on brachial artery (BA) VEF in healthy breakfast eaters. A total of nine healthy individuals (4 females and 5 males) either had breakfast between 830 and 900 or skipped it and had lunch between 1200 and 1230, followed by a 3-h rest period until 1530. For BA VEF evaluation, flow-mediated dilation (FMD) was measured by ultrasound before and after breakfast and lunch. FMD was calculated as the percent change in BA diameter normalized to the shear rate area under the curve (FMD/SRAUC). Blood glucose, plasma insulin, and plasma free fatty acid levels in capillaries were measured before and after breakfast and lunch. At 1530, the Eating trial, but not the Skipping trial, significantly increased FMD/SRAUC from baseline (P = 0.006). The Skipping trial showed significantly lower changes in FMD/SRAUC from 830 than the Eating trial at 1530 (P < 0.001). We found a significant inverse correlation between changes in FMD/SRAUC between 830 and 1530 and peak glucose levels after lunch (r = -0.882, P < 0.001) and with an incremental area under the curve for glucose between 830 and 1530 (r = -0.668, P < 0.001). These results suggest that a single bout of breakfast skipping can suppress BA VEF in the afternoon because of postlunch hyperglycemia.NEW & NOTEWORTHY Skipping breakfast does not affect vascular endothelial function (VEF) before lunch. However, after lunch on normal meals (i.e., not oral glucose tolerance test), VEF was found to be lower in those who skipped breakfast than those who ate breakfast. Such reduced postlunch VEF after skipping breakfast was associated with postprandial hyperglycemia. These results provide important insight into the impact of eating breakfast on VEF and glycemic control in healthy adults.

Increment in Oncovascular Risk Factors and Psychological Distress and Unaltered Vascular Endothelial Function with Advancement of the Stages in Newly Diagnosed Patients with Primary Breast Cancer

Abstract Background and Aims Oncovascular risk factors are common to both cardiovascular diseases and cancer. Adipocytokines, cell adhesion molecules, and psychological distress may have roles in disease progression. Materials and Methods Eighty subjects including healthy control and patients of different stages of newly diagnosed breast cancer were recruited. The levels of psychological distress, oncovascular risk factors, and endothelial function were estimated. Results Soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), adiponectin, and scores of anxiety (Generalized Anxiety Disorder-7 [GAD-7]), depression (Patient Health Questionnaire-9 [PHQ-9]), and perceived stress (Perceived Stress Scale [PSS]) increased with increasing stages of the disease. Vascular endothelial function (brachial artery flow-mediated dilation) among the different stages and healthy controls was comparable. Adiponectin (area under the curve [AUC] = 0.755 at 1.66 µg/mL, sensitivity 70% and specificity 80%), sICAM-1 (AUC = 0.769 at 264 pg/mL, sensitivity 80% and specificity 75%), and sVCAM-1 (AUC = 0.934 at 165 ng/mL, sensitivity 88% and specificity 85%) are useful in the breast cancer diagnosis with receiver operating characteristic curves. PSS (r = 0.688, p &lt; 0.001), PHQ-9 (r = 0.633, p &lt; 0.001), GAD-7 scores (r = 0.674, p &lt; 0.001) and levels of sICAM-1 (r = 0.480, p &lt; 0.001) and sVCAM-1 (r = 0.577, p &lt; 0.00) correlated with disease progression. Perceived stress had maximum independent association with the disease progression. Oncovascular risk factors correlated with perceived stress, anxiety, and depression. Conclusion Increment in oncovascular risk factors, psychological distress, and their associations were observed with increasing stages of breast cancer. Intervention to prevent incidence of coronary heart diseases and appropriate psychological counseling for patients with breast cancer may be considered for bringing forth better treatment outcome.

Effects of Lower Limb Heat Therapy, Exercise Training, or a Combined Intervention on Vascular Function: A Randomized Controlled Trial.

To compare the effects of 8 weeks of no intervention (CON), lower limb heat therapy (HEAT), moderate-intensity exercise training (EX), or combined training and therapy (HEATEX) in young, healthy recreationally active adults. Sixty participants (23 ± 3 years, 30 females) were randomly allocated into either CON (n = 15), HEAT (n = 15), EX (n = 14), or HEATEX (n = 16). The primary outcome was vascular function, assessed through brachial artery flow-mediated dilation tests (BA FMD). Secondary measures included arterial stiffness (pulse wave velocity, PWV); cardiorespiratory fitness (VO2peak); body composition; and quadriceps muscle strength. There were no differences in BA FMD between the groups before and after the interventions (all p > 0.05). Both interventions with a heating component were associated with within-group reductions in carotid-femoral PWV, and increases in absolute and relative VO2peak after 8 weeks (HEAT: ∆-0.27 [-0.53, -0.02] m/s, ∆0.18 [0.06, 0.29] L/min, ∆2.18 [0.60, 3.76] ml/kg/min, respectively; HEATEX: ∆-0.33 [-0.58, -0.09], ∆0.21 [0.11, 0.32] L/min, ∆2.59 [1.06, 4.12] ml/kg/min, respectively), but no between-group differences were observed (p = 0.25, p = 0.21, and p = 0.55, respectively). There was also a within-group decrease in body fat percentage with EX (∆-1.37 [-2.45, -0.29] %), but no changes in leg strength in any of the groups (p = 0.79). This randomized controlled trial is the first to examine the efficacy of lower limb heating against traditionally prescribed exercise training. In our young cohort, 8 weeks of training and/or therapy was insufficient to improve vascular function. More intense protocols and longer interventions involving lower limb heating may be required to elicit improvements in health outcomes.

Unexplored Opportunities of Utilizing Food Waste in Food Product Development for Cardiovascular Health.

Global food production leads to substantial amounts of agricultural and food waste that contribute to climate change and hinder international efforts to end food insecurity and poverty. Food waste is a rich source of vitamins, minerals, fibers, phenolic compounds, lipids, and bioactive peptides. These compounds can be used to create food products that help reduce heart disease risk and promote sustainability. This review examines the potential cardiovascular benefits of nutrients found in different food waste categories (such as fruits and vegetables, cereal, dairy, meat and poultry, and seafood), focusing on animal and clinical evidence, and giving examples of functional food products in each category. Current evidence suggests that consuming fruit and vegetable pomace, cereal bran, and whey protein may lower the risk of cardiovascular disease, particularly in individuals who are at risk. This is due to improved lipid profile, reduced blood pressure and increased flow-mediated dilation, enhanced glucose and insulin regulation, decreased inflammation, as well as reduced platelet aggregation and improved endothelial function. However, the intervention studies are limited, including a low number of participants and of short duration. Food waste has great potential to be utilized as cardioprotective products. Longer-term intervention studies are necessary to substantiate the health claims of food by-products. Technological advances are needed to improve the stability and bioavailability of bioactive compounds. Implementing safety assessments and regulatory frameworks for functional food derived from food waste is crucial. This is essential for maximizing the potential of food waste, reducing carbon footprint, and improving human health.

Impaired arterial dilation and increased NOX2 generated oxidative stress in subjects with ataxia-telangiectasia mutated (ATM) kinase

BackgroundSubjects with mutations in the Ataxia-Telangiectasia mutated (ATM) gene encoding for ATM kinase have a greater predisposition to develop atherosclerosis, but the mechanism behind this phenomenon is not yet understood. NADPH oxidase type 2 may play a role in this process, leading to endothelial dysfunction and an increased susceptibility to thrombosis. The purpose of this study was to assess the redox state in individuals with ATM mutations and determine its impact on endothelial function. MethodsIn this cross-sectional study, twenty-seven children with ataxia telangiectasia (AT) (13 males and 14 females, mean age 15.1 ± 7.6 years) were compared with 27 controls (13 males and 14 females, mean age 14.6 ± 8.4 years) matched for age and gender. Additionally, 29 AT parents with heterozygous mutation of ATM (h-ATM) gene, and 29 age- and gender-matched controls were included. Endothelial function was evaluated through brachial flow-mediated dilation (FMD) and the assessment of nitric oxide (NO) bioavailability. Oxidative stress was evaluated by measuring serum activity of soluble NOX2-dp (sNOX2-dp), hydrogen peroxide (H2O2) production, and hydrogen breakdown activity (HBA). Thrombus formation was assessed through the Total Thrombus Formation Analysis System (T-TAS). ResultsAT children and parents with heterozygous ATM mutations exhibited significantly lower FMD, HBA, and NO bioavailability as compared to age and gender matched controls. AT children and ATM carrier of heterozygous ATM mutations had significantly higher concentrations of sNOX2-dp and H2O2 as compared to controls. Compared to the respective controls, AT children and their parents, who carried heterozygous ATM mutation, showed an accelerated thrombus growth as revealed by reduced occlusion time. Multivariable linear regression analysis revealed that sNOX2 (standardized coefficient β: −0.296; SE: 0.044; p = 0.002) and NO bioavailability (standardized coefficient β: 0.224; SE: 0.065; p = 0.02) emerged as the only independent predictive variables associated with FMD (R2: 0.44). ConclusionsThis study demonstrates that individuals with ATM mutations experience endothelial dysfunction, increased oxidative stress, and elevated thrombus formation. These factors collectively contribute to the heightened susceptibility of these individuals to develop atherosclerosis.

Comparative effects of sacubitril/valsartan and ACEI/ARB on endothelial function and arterial stiffness in patients with heart failure: a protocol for systematic review and meta-analysis

IntroductionHeart failure (HF) is a complex syndrome that affects millions of people worldwide and leads to significant morbidity and mortality. Sacubitril/valsartan, a combination drug consisting of a neprilysin inhibitor and...

Identifying the Role of Flow-Mediated Dilatation Assessment in Acute Coronary Syndromes: A Systematic Review.

In the context of the global burden of cardiovascular disease, the development of novel, patient-targeted diagnostic and therapeutic strategies is of paramount importance. Acute coronary syndromes (ACS) comprise a subset of cardiovascular disease, with constantly increasing prevalence requiring urgent attention. Flow-mediated dilatation (FMD), a noninvasive method for the evaluation of endothelial function, has been previously implemented in patients with ACS. A systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was conducted in order to identify all relevant studies assessing the implementation of FMD among patients with ACS. Our review reflects an effort to present all available data regarding the role of FMD to date, a valuable noninvasive and easy accessible diagnostic tool, in the prognosis of patients with ACS. FMD evaluation in patients with ACS reveals a decline in values, indicative of the presence of endothelial function among this distinct patient group. FMD has also been used to assess the response to various treatments, as well as to predict major adverse cardiovascular events. Dynamic responses to interventions highlights its potential in the evolving field of interventional cardiology.

Association between endothelial function and skin advanced glycation end-products (AGEs) accumulation in a sample of predominantly young and healthy adults

BackgroundIn populations with chronic disease, skin autofluorescence (SAF), a measure of long-term fluorescent advanced glycation end-products (AGEs) accumulation in body tissues, has been associated with vascular endothelial function, measured using flow-mediated dilation (FMD). The primary aim of this study was to quantify the relationship between endothelial function and tissue accumulation of AGEs in adults from the general population to determine whether SAF could be used as a marker to predict early impairment of the endothelium.MethodsA cross-sectional study was conducted with 125 participants (median age: 28.5 y, IQR: 24.4–36.0; 54% women). Endothelial function was measured by fasting FMD. Skin AGEs were measured as SAF using an AGE Reader. Participant anthropometry, blood pressure, and blood biomarkers were also measured. Associations were evaluated using multivariable regression analysis and were adjusted for significant covariates.ResultsFMD was inversely correlated with SAF (ρ = -0.50, P < 0.001) and chronological age (ρ = -0.51, P < 0.001). In the multivariable analysis, SAF, chronological age, and male sex were independently associated with reduced FMD (B [95% CI]; -2.60 [-4.40, -0.80]; -0.10 [-0.16, -0.03]; 1.40 [0.14, 2.67], respectively), with the multivariable model adjusted R2 = 0.31, P < 0.001.ConclusionsHigher skin AGE levels, as measured by SAF, were associated with lower FMD values, in a predominantly young, healthy population. Additionally, older age and male participants exhibited significantly lower FMD values, corresponding with compromised endothelial function. These results suggest that SAF, a simple and inexpensive marker, could be used to predict endothelial impairment before the emergence of any structural artery pathophysiology or classic cardiovascular disease risk markers.Trial registrationThe study was prospectively registered with the Australian New Zealand Clinical Trials Registry (ACTRN12621000821897) and concurrently entered into the WHO International Clinical Trials Registry Platform under the same ID number.

E-Selectin and Asymmetric Dimethylarginine Levels in Adult Cyanotic Congenital Heart Disease: Their Relation to Biochemical Parameters, Vascular Function, and Clinical Status.

Background and Aim: Patients with cyanosis secondary to congenital heart disease (CHD) are characterized by erythrocytosis and increased blood viscosity, which contribute to endothelial dysfunction, increased arterial stiffness, and impaired vascular function, which may affect the final clinical presentation. Asymmetric dimethylarginine (ADMA) and e-selectin (e-sel) are valuable biomarkers for endothelial and vascular dysfunction. Their concentration levels in blood serum have the potential to be an accessible tool that reflects the severity of the disease. We aimed to assess e-sel and ADMA levels and their relationship with the clinical status and endothelial and vascular function. Methods: A cross-sectional study, including 36 adult CHD cyanotic patients [(17 males) (42.3 ± 16.3 years)] with an arterial blood oxygen saturation less than 92% and 20 healthy controls [(10 males) (38.2 ± 8.5 years)], was performed. All the patients underwent a clinical examination, blood testing, and cardiopulmonary tests. Their endothelial function was assessed using the intima media thickness and flow-mediated dilatation. Vascular function, using applanation tonometry methods, was determined using the aortic systolic pressure, aortic pulse pressure, augmentation pressure, augmentation index, pulse pressure amplification, and pulse wave velocity. Results: The concentrations of e-sel and ADMA were significantly higher in the patients with CHD. The E-sel levels correlated positively with red blood cells, hemoglobin concentration, hematocrit, and augmentation pressure; they correlated negatively with blood oxygen saturation, the forced expiratory one-second volume, forced vital capacity, and oxygen uptake. The ADMA levels were found to correlate only with age. Conclusions: The E-sel level, unlike ADMA concentration, reflects the severity of erythrocytosis and hypoxia and, thus, the physical status of patients with cyanotic CHD.

Differences in cardiovascular risk factors associated with sex and gender identity, but not gender expression, in young, healthy cisgender adults.

Sex differences exist in cardiovascular disease risk factors including elevated blood pressure and arterial stiffness, and decreased endothelial function in males compared to females. Feminine gender expression may be associated with elevated risk of acute coronary syndrome. However, no study has investigated the associations between sex, gender identity, and gender expression and cardiovascular disease risk factors in young adults. One hundred and thirty participants (22 ± 3 years) underwent assessments of hemodynamics, arterial stiffness [pulse wave velocity (PWV)], and brachial artery endothelial function (flow-mediated dilation; %FMD). Participants completed a questionnaire capturing sex category (50 male/80 female), gender identity category (49 men/79 women/2 non-binary), and aspects of gender expression assessed by the Bem Sex Role Inventory-30 (39 androgynous/33 feminine/29 masculine/29 undifferentiated). Sex/gender identity category groups were compared using unpaired t-tests and gender expression groups compared using one-way ANOVAs. Resting systolic and mean arterial pressure (p < 0.01) were elevated in males vs. females. Central PWV was elevated in males [median (interquartile range): 6.4 (1.8) vs. 5.8 (2.2) m/s, p = 0.02]; however, leg and arm PWV were not different between sexes. %FMD was elevated in males vs. females, after accounting for a larger baseline artery diameter in males (8.8 ± 3.3% vs. 7.2 ± 3.1%, p = 0.02); since the majority of participants were cisgender, the same results were found examining gender identity (men vs. women). There were no differences across gender expression groups (p > 0.05). Sex/gender identity category, but not gender expression, influence cardiovascular risk factors (blood pressure, arterial stiffness, endothelial function) in cisgender adults; further research is needed in gender-diverse populations.

Vascular endothelial function and its response to moderate-intensity aerobic exercise in trained and untrained healthy young men

30 min of moderate-intensity aerobic exercise per day is recommended, but the response and adaptation of endothelial function (EF) to this exercise remains controversial. The purpose of this study was to determine the changes in EF in endurance trained and untrained individuals before and after this exercise and to compare the differences between trained and untrained individuals. Twelve endurance-trained male college athletes (trained group) and 12 untrained male college students (untrained group) performed a 30-min run at an intensity of 60% VO2max. Brachial artery flow-mediated dilation (FMD) was measured before exercise, 30 min and 60 min after exercise, and the following morning. Resting diameter and maximum diameter showed large time effects (p < 0.001, η2 = 0.533; p < 0.001, η2 = 0.502). Resting diameters at 30 and 60 min after exercise were higher than before exercise in both the untrained and trained groups (p < 0.05), and maximum diameters at 30 min after exercise were higher than before exercise in both the untrained and trained groups (p < 0.01). Resting diameter and maximum diameter also exhibited some group effects (p = 0.055, η2 = 0.157; p = 0.041, η2 = 0.176). Resting diameters and maximum diameters were higher in the trained group than in the untrained group before exercise (p < 0.05). FMD (%) showed no time, group, or time-group interaction effects. 30 min of moderate-intensity aerobic exercise can increase resting and maximal arterial diameters in both trained and untrained young men, but has no effect on FMD. Long-term endurance training has the potential to increase resting and maximal arterial diameters in young men, but not necessarily FMD.

T-cell senescence was correlated with early atherosclerosis inpatients with systemic lupus erythematosus.

To investigate the correlation between T-cell senescence with the atherosclerosis markers in patients with systemic lupus erythematosus (SLE). The study participants were 40 female SLE patients aged 18-45 years who met the 2019 EULAR/ACR criteria and 40 healthy individuals. The atherosclerosis markers were investigated using the Doppler ultrasonography examinations to measure the cIMT (carotid intima-media thickness) and flow-mediated dilation (FMD) and serological markers using soluble ICAM-1 and VCAM-1. Flow cytometry of CD4+CD57+, CD8+CD57+, CD4+CD28null, and CD8+CD28null T cells were used to assess the immunosenescence markers. The cIMT (p < .001), sICAM-1 (p < .001), and sVCAM-1 (p < .001) were significantly higher in SLE patients compared with control, while FMD was significantly lower in SLE patients (p < .001). The percentages of all T-cell senescence markers are also significantly higher in SLE patients than in healthy individuals. Positive correlations were shown between cIMT with the CD4+CD57+ (R = .301, p = .005), CD4+CD28null (R = .448, p < .001), and CD8+CD28null (R = .422, p < .001). Conversely, negative correlations were demonstrated between the FMD with CD4+CD57+ (R = -.236, p = .023), CD8+CD57+ (R = -.409, p < .001), CD4+CD28null (R = -.422, p < .001), and CD8+CD28null (R = -.318, p = .003). The soluble markers of sICAM-1 and sVCAM-1 were also positively correlated with the T-cell senescence markers. Early sign of atherosclerosis was demonstrated in patients with SLE in this study. T-cell senescence markers had significant correlations with the atherosclerosis markers, including the cIMT, FMD, and soluble adhesion molecules levels. Understanding the link between immunosenescence and atherosclerosis might help to identify a new method for early detection and treatment of atherosclerosis in SLE.