Flow-mediated Dilation Values Research Articles

The Influence of Resting Retrograde Shear Rate on Endothelial Function as Assessed by Flow Mediated Dilation

Shear stress profiles are an important determinant of endothelial function. Unidirectional blood flow enhances mean shear and protects endothelial function, whereas increased retrograde and oscillatory shear favors a proatherogenic environment. In this regard, acutely increasing retrograde shear has been shown to impair endothelial function. Also, previous studies have reported an elevation in retrograde shear in older adults that has been suggested to contribute to impaired endothelial function with age. However, the impact of having elevated retrograde shear at rest on endothelial function remains unclear. Therefore, we aimed to assess the associations between resting shear patterns and endothelial function, as measured by flow-mediated dilation (FMD) in a cohort of young and older adults. We hypothesized that higher retrograde shear rate and oscillatory shear index at rest would be related to a lower FMD value. Method: A total of 60 participants, 30 young adults (24 ± 5 years) and 30 older adults (62 ± 9 years), were studied. Resting brachial artery blood flow was measured using duplex Doppler ultrasound and retrograde shear rate and oscillatory shear index were calculated. Brachial artery FMD was used as a measure of endothelial function. Pearson correlations were used to investigate the associations between FMD, resting shear patterns, and age. Result: FMD was significantly lower in older compared to young adults (4.9 ± 2.7% vs. 7.6 ± 3.2%, p < 0.01). Both retrograde shear rate and oscillatory shear index tended to be greater in older adults (-20.7 ± 15.1 s−1 vs. -15.2 ± 17 s−1, p = 0.062, and 10.7 ± 8% vs. 7.9 ± 8.0%, p = 0.056, respectively). FMD was not correlated with retrograde shear rate (r = -0.18, p = 0.17), or oscillatory shear index (r = -0.21, p = 0.11) in the entire cohort or in the young and older group alone. However, FMD, retrograde shear rate, and oscillatory index were moderately correlated with age: FMD (r = -0.45, p < 0.01), retrograde shear rate (r = -0.32, p = 0.012), and oscillatory shear index (r = 0.33, p < 0.01). Conclusion: These preliminary results suggest that resting retrograde shear and oscillatory shear index are not associated with reduced endothelial function in a cohort of young and old adults. Nevertheless, age-associated reductions in endothelial function and elevated retrograde shear were observed. This project was supported by the College of Nursing and Health Innovation. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Association between triglyceride-glucose index and endothelial dysfunction.

Triglyceride-glucose (TyG) index, a simple surrogate marker for insulin resistance (IR), has been reported as an independent predictor of arterial structural damage and future cardiovascular events. The association between TyG index and endothelial dysfunction remains uncertain. The purpose of this study was to investigate the association between TyG index and endothelial dysfunction. Endothelial dysfunction was measured using flow-mediated dilation (FMD). A total of 840 subjects, who voluntarily accepted FMD measurement at the Health Management Department of Xuanwu Hospital from October 2016 to January 2020, were included in this study. TyG index was calculated as Ln [fasting triglyceride (TG)(mg/dL) × fasting plasma glucose (FPG) (mg/dL)/2]. The mean age was 59.92 ± 10.28 years and 559 (66.55%) participants were male. The TyG index was correlated with FMD values (P = 0.022). Each unit increment in TyG index was associated with lower FMD values (β = -0.330, 95%CI -0.609 to -0.052, P = 0.020) after adjusting for covariates. Age (β = -0.069, 95%CI -0.088 to -0.051, P < 0.001), female (β = 0.592, 95%CI 0.172 to1.012, P = 0.006), smoking (β = -0.430, 95%CI -0.859 to -0.002, P = 0.049) and hypertension (β = -0.741, 95%CI -1.117 to -0.365, P < 0.001) were also independent predictors for endothelial dysfunction. A significant association between the TyG index and endothelial dysfunction was found only in populations younger than 60 years (β = -0.843, 95%CI -1.371 to -0.316, P = 0.002), females (β = -0.612, 95%CI -1.147 to -0.077, P = 0.025), and populations without diabetes mellitus (DM) (β = -0.594, 95%CI -1.042 to -0.147, P = 0.009). Subjects with an elevated TyG index are more likely to have endothelial dysfunction, particularly in populations without DM.

Acute and short-term beetroot juice nitrate-rich ingestion enhances cardiovascular responses following aerobic exercise in postmenopausal women with arterial hypertension: A triple-blinded randomized controlled trial

BackgroundThe increase in blood pressure (BP) levels in the postmenopausal period can be partly explained by the decrease in nitric oxide synthases (NOS). ObjectiveTo investigate the acute and one-week effects of beetroot juice nitrate-rich (BRJ-NO3−rich) ingestion on cardiovascular and autonomic performance in response to submaximal aerobic exercise in postmenopausal women with systemic arterial hypertension (SAH) who are physically inactive. MethodsFourteen postmenopausal women with SAH [mean (SD) age: 59(4) y; BMI (kg/m2): 29.2(3.1)] completed submaximal aerobic exercise bouts after an acute and a one-week intervention with BRJ in a placebo-controlled, randomized, triple-blind, crossover design. Participants ingested either BRJ (800 mg of NO3−) or placebo acutely and drank either BRJ (400 mg of NO3−) or placebo every day for the next six days. After two and ½ hours, they performed a session of aerobic submaximal aerobic exercise, and their systolic BP (SBP) and diastolic BP (DBP), flow-mediated dilation (FMD), heart rate (HR) recovery, and HR variability were measured. ResultsIn the post-exercise recovery period, SBP dropped significantly in the BRJ-NO3−rich group (−9.28 mmHg [95%CI: −1.68 to −16.88] ES: −0.65, p = 0.019) compared to placebo after acute ingestion. The FMD values increased after acute BRJ-NO3−rich on post-exercise (3.18 % [0.36 to 5.99] ES: 0.87, p = 0.031). After the one-week intervention, FMD values were higher in the BRJ-NO3−rich group before (4.5 % [1.62 to 7.37] ES: 1.21, p = 0.005) and post-exercise measurements (4.2 % [1.52 to 6.87] ES: 1.22, p = 0.004) vs. placebo. HRV indices with remarkable parasympathetic modulation to heart recovered faster on the BRJ-NO3−rich group than placebo group. No between-group differences were identified in values of HR post-exercise recovery in the 30s, 60s, 120s, 180s, and 300s. ConclusionsAcute and short-term BRJ-NO3−rich ingestion may enhance cardiovascular and autonomic behavior in response to aerobic exercise in postmenopausal women diagnosed with SAH. Clinical trial registry numberhttps://clinicaltrials.gov/ct2/show/NCT05384340.

Enhanced external counterpulsation improves sleep quality in chronic insomnia: A pilot randomized controlled study

PurposeTo investigate the short-term efficacy of enhanced external counterpulsation (EECP) on chronic insomnia. MethodsThis is a pilot randomized, participant-blind, and sham-controlled study. Forty-six participants with chronic insomnia were randomly assigned in a 1:1 ratio to receive EECP or sham EECP intervention (total of 35 sessions with 45 min each). The primary outcome was Pittsburgh Sleep Quality Index (PSQI). The secondary outcomes included sleep diary, Hospital Anxiety and Depression Scale (HADS), Short-Form Health Survey (SF12), flow mediated dilation (FMD), serum biomarkers of melatonin, cortisol, interleukin-6, and high sensitivity C-reactive protein. Outcomes were assessed after treatment and at 3-month follow-up. ResultsThe PSQI was significantly decreased in both EECP and sham groups after 35-session intervention (13.74 to 6.96 in EECP and 13.04 to 9.48 in sham), and EECP decreased PSQI more than sham EECP (p = 0.009). PSQI in two groups kept improved at 3-month follow-up. After treatment, the total sleep time, sleep efficiency, FMD value and SF12 mental component of EECP group were significantly improved, and group differences were found for these outcomes. At follow-up, total sleep time, sleep efficiency and SF12 mental component of EECP group remained improved, and group difference for SF12 mental component was found. Post-treatment and follow-up HADS-A significantly decreased in both groups, with no differences between groups. Post-treatment serum biomarkers showed no differences within and between groups. LimitationLack of objective sleep measurement. ConclusionEECP could improve sleep quality and mental quality of life in chronic insomnia and the therapeutic effect maintained for 3 months.

Brachial artery FMD and carotid artery IMT in glaucoma

Aims/Purpose: The purpose of the study was to assess the ultrasound measurements of the brachial artery flow‐mediated dilation (FMD) and carotid artery intima‐media thickness (IMT) and their relationship in glaucoma patients.Methods: Thirty‐seven patients with glaucoma and thirty‐one healthy controls were included in the study. All glaucoma patients and controls underwent ultrasound measurement of FMD of the brachial artery and ultrasound measurement of IMT of the carotid artery.Results: The mean values of brachial FMD were significantly lower among the glaucoma compared with controls (15.3 ± 9.5% vs 19.8 ± 9.3%, p = 0.04). No significant difference was found in carotid IMT (1.2 ± 0.4 vs. 1.1 ± 0.3, p = 0.4), and brachial artery diameter at rest (4.7 ± 0.6 vs. 4.9 ± 0.3, p = 0.2) between the glaucoma patients and controls. The significant difference in brachial artery diameter in hyperemia between the glaucoma patients and controls (5.4 ± 0.6 vs. 5.9 ± 0.4, p = 0.002) was found. A negative correlation among brachial FMD and carotid IMT as well as among brachial FMD and brachial artery diameter at rest was found.Conclusions: Impaired brachial FMD indicates presence of systemic vascular endothelial dysfunction in glaucoma; glaucoma patients with lower values of the brachial FMD are at increased risk of having thickened carotid IMT.

Flow Mediated Dilation in Systemic Sclerosis: Association with clinical findings, capillaroscopic patterns and endothelial circulating markers

AimEndothelial dysfunction represents a key feature of the pathological process underlying micro and macro-vascular damage in Systemic Sclerosis (SSc). This study aims to improve knowledge of the physiopathology of vascular damage in SSc through the assessment of the endothelial dysfunction by Flow Mediated Dilation (FMD) and serum levels of circulating endothelial dysfunction markers and the correlation of macrovascular damage with clinical findings and microvascular capillaroscopic patterns. Methods57 SSc patients and 37 healthy subjects were recruited. All included subjects underwent radial artery FMD test and Nailfold Video-Capillaroscopy; serum levels of Vascular Endothelial Growth Factor (VEGF), Vascular Cell Adhesion Molecule-1 (VCAM-1) and angiopoietin-2 were evaluated. ResultsCompared to healthy subjects, in SSc patients lower FMD and higher time needed to obtain the maximal FMD responsewere observed, whereas serum levels of VEGF, VCAM-1, and angiopoietin-2 were significantly higher. The impairment of FMD values was associated with disease duration, pulmonary arterial hypertension, and digital ulcers and correlates with greater microvascular damage evaluated by Nailfold Video-Capillaroscopy… An inverse relationship between VEGF, angiopoietin-2, VCAM-1 levels and FMD was observed, but only VEGF and angiopoietin-2 were significantly higher in patients with digital ulcers and pulmonary arterial hypertension. ConclusionsFMD ultrasound test and circulating levels of endothelial dysfuncion markers could be useful as biomarkers of vasculopathy and could be a helpful tool in the overall assessment of vascular injury in Systemic Sclerosis patients.

Serum Fibroblast Growth Factor 23 Levels are Associated with Vascular Smooth Muscle Dysfunction in Type 2 Diabetes.

Increased level of serum fibroblast growth factor 23 (FGF23) is a hallmark of abnormal phosphate metabolism in patients with chronic kidney disease (CKD) and is recently shown to be associated with the risk of cardiovascular disease even in those without CKD. This study investigated the association between serum FGF23 levels and vascular function in patients with type 2 diabetes. This was a cross-sectional study involving 283 Japanese patients with type 2 diabetes. Flow-mediated dilatation (FMD) and nitroglycerin-mediated dilatation (NMD) of the brachial artery were measured via ultrasonography to evaluate vascular endothelial and smooth muscle functions, respectively. Serum intact FGF23 levels were determined via a sandwich enzyme-linked immunosorbent assay. The median values of FMD, NMD, and serum FGF23 were 6.0%, 14.0%, and 27.3 pg/mL, respectively. The serum FGF23 levels were inversely associated with NMD but not with FMD, and the association was independent of atherosclerotic risk factors, estimated glomerular filtration rate (eGFR), and serum phosphate levels. Furthermore, the relationship between serum FGF23 levels and NMD was modified by kidney function, which was pronounced in subjects with normal kidney function (eGFR ≥ 60 mL/min/1.73 m2). Serum FGF23 levels are independently and inversely associated with NMD in patients with type 2 diabetes, particularly in those with normal kidney function. Our results indicate that FGF23 is involved in vascular smooth muscle dysfunction and that increased serum levels of FGF23 may serve as a novel biomarker for vascular smooth muscle dysfunction in patients with type 2 diabetes.

Hypoglossal Nerve Stimulation and Cardiovascular Outcomes for Patients With Obstructive Sleep Apnea

Sham-controlled trials are needed to characterize the effect of hypoglossal nerve stimulation (HGNS) therapy on cardiovascular end points in patients with moderate-severe obstructive sleep apnea (OSA). To determine the effect of therapeutic levels of HGNS, compared to sham levels, on blood pressure, sympathetic activity, and vascular function. This double-blind, sham-controlled, randomized crossover therapy trial was conducted from 2018 to 2022 at 3 separate academic medical centers. Adult patients with OSA who already had an HGNS device implanted and were adherent and clinically optimized to HGNS therapy were included. Participants who had fallen asleep while driving within 1 year prior to HGNS implantation were excluded from the trial. Data analysis was performed from January to September 2022. Participants underwent a 4-week period of active HGNS therapy and a 4-week period of sham HGNS therapy in a randomized order. Each 4-week period concluded with collection of 24-hour ambulatory blood pressure monitoring (ABPM), pre-ejection period (PEP), and flow-mediated dilation (FMD) values. The change in mean 24-hour systolic blood pressure was the primary outcome, with other ABPM end points exploratory, and PEP and FMD were cosecondary end points. Participants (n = 60) were older (mean [SD] age, 67.3 [9.9] years), overweight (mean [SD] body mass index, calculated as weight in kilograms divided by height in meters squared, 28.7 [4.6]), predominantly male (38 [63%]), and had severe OSA at baseline (mean [SD] apnea-hypopnea index, 33.1 [14.9] events/h). There were no differences observed between active and sham therapy in 24-hour systolic blood pressure (mean change on active therapy, -0.18 [95% CI, -2.21 to 1.84] mm Hg), PEP (mean change on active therapy, 0.11 [95% CI, -5.43 to 5.66] milliseconds), or FMD (mean change on active therapy, -0.17% [95% CI, -1.88% to 1.54%]). Larger differences between active and sham therapy were observed in a per-protocol analysis set (n = 20) defined as experiencing at least a 50% reduction in apnea-hypopnea index between sham and active treatment. In this sham-controlled HGNS randomized clinical trial, mean 24-hour systolic blood pressure and other cardiovascular measures were not significantly different between sham and active HGNS therapy. Several methodologic lessons can be gleaned to inform future HGNS randomized clinical trials. ClinicalTrials.gov Identifier: NCT03359096.

A novel method that can be used in both the diagnosis and treatment of peripheral arterial disease in diabetics: vibration-mediated dilation.

The growing incidence of diabetes and the increasing life expectancy of the diabetic population worldwide has increased the number of diabetic vascular complications occurring in cardiology practice. As current treatment and prevention methods are less effective in this patient group, there is a need for new treatment methods in this area. Exercise, which reduces metabolic and vascular problems associated with diabetes, often becomes impossible, especially in advanced-stage patients who need exercise the most. Since exercise and flow-mediated dilation (FMD) are effective by stimulating mechanotransduction mechanisms on the endothelium, it can be expected that the same mechanisms could also be stimulated by direct vibration. In order to test this hypothesis, in this study, a group of 20 type 2 diabetes patients (11 males, age 56.80 ± 11.05 years and diagnosed for 15.35 ± 8.61 years) were examined via the application of FMD and vibration-mediated dilation (VMD). We performed vibration for five minutes with 20-Hz frequency and 3-mm vertical amplitude, to the same side forearm, with a 30-minute interval. Using a 10-MHz linear echo probe, brachial artery diameter and flow velocities were recorded for 10 minutes before and at two-minute intervals after the FMD and VMD applications. Then brachial artery flow and resistance were calculated at each stage. In the first minute after FMD and VMD applications, brachial artery diameter and flow velocities increased significantly, and vascular resistance decreased significantly. None of the corresponding FMD or VMD parameters in the first minute was different. The artery diameters in the first minute after FMD and VMD were increased by 6.04 ± 5.29 and 5.49 ± 5.21%, respectively. At the tenth minute, these values decreased to 1.73 ± 3.21 and 2.05 ± 3.31%. In the FMD series, all parameters except brachial artery diameter returned to their baseline values after the fourth minute. After VMD, all parameters also decreased after the first minute, but the recovery was much slower. At each stage after the first minute, the VMD averages were higher than the baseline value and their corresponding FMD values. The results of this study indicated that vibration may be a powerful, long-lasting and feasible treatment option in patients with peripheral perfusion failure, developed due to diabetic macro- and microvascular complications.

Inferior vena cava wall thickness is associated with the presence and severity of cardiovascular disease

Abstract Background Venous hypertrophy is a pathological condition that is commonly observed as individuals age. However, the clinical index and significance of venous hypertrophy are not yet fully understood. Purpose The purpose of this study was to clarify the relationship between clinical venous hypertrophy and cardiovascular disease (CVD). Methods A total of 407 patients who underwent echocardiography and evaluation of their endothelial function during a medical checkup were included in the study. Clinical venous hypertrophy was evaluated by measuring the thickness of the inferior vena cava wall (IVCWT) using echocardiography. Endothelial function was evaluated using flow-mediated dilation (FMD). CVD included ischemic heart disease, heart failure, and atrial fibrillation. The patients were divided into two groups based on the median value of IVCWT and their clinical characteristics were compared. Results The IVCWT was found to be normally distributed with a median value of 1.25 mm (p &amp;lt; 0.001). The high-IVCWT group was found to be older (62.1 ± 13.1 years versus 58.1 ± 12.0 years, p = 0.001), had a higher ratio of males (72.4% versus 60.3%, p = 0.010), a higher ratio of CVD (7.4% versus 2.7%, p = 0.002), a lower left ventricular ejection fraction (62.1 ± 10.9% versus 64.6 ± 7.6%, p = 0.009), higher levels of B-type natriuretic peptide (21.0 [12.1-48.4] pg/mL versus 14.0 [8.9-33.5] pg/mL, p = 0.039), and lower FMD values (5.36 ± 2.33% versus 5.99 ± 2.73%, p = 0.012) compared to the low-IVCWT group. Multivariate analysis revealed that IVCWT and age were independent factors for the prevalence of CVD (IVCWT: Odds ratio 2.563, 95% confidence interval 1.258-5.563, p = 0.009; age: Odds ratio 1.049, 95% confidence interval 1.021-1.078, p &amp;lt; 0.001). The receiver-operating characteristic analysis found that the best cut-off values for IVCWT and FMD to identify CVD were 1.60 mm and 0.49, respectively (IVCWT: area under the curve 0.731, p &amp;lt; 0.001, sensitivity 51%, specificity 90%; FMD: area under the curve 0.739, p &amp;lt; 0.001, sensitivity 80%, specificity 61%). Conclusion The results of this study suggest that IVCWT is associated not only with age, but also with the presence and severity of CVD.Figure 1Figure 2

People with Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Exhibit Similarly Impaired Vascular Function

BackgroundThis study aimed to compare flow-mediated dilation values between individuals with long COVID, individuals with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and healthy age-matched controls to assess the potential implications for clinical management and long-term health outcomes. MethodsA case-case-control approach was employed, and flow-mediated dilation measurements were obtained from 51 participants (17 long COVID patients, 17 ME/CFS patients, and 17 healthy age-matched controls). Flow-mediated dilation values were analyzed using 1-way analysis of variance for between-group comparisons. ResultsResults revealed significantly impaired endothelial function in both long COVID and ME/CFS groups compared with healthy age-matched controls as determined by maximum % brachial artery diameter post-occlusion compared with pre-occlusion resting diameter (6.99 ± 4.33% and 6.60 ± 3.48% vs 11.30 ± 4.44%, respectively, both P < .05). Notably, there was no difference in flow-mediated dilation between long COVID and ME/CFS groups (P = .949), despite significantly longer illness duration in the ME/CFS group (ME/CFS: 16 ± 11.15 years vs long COVID: 1.36 ± 0.51 years, P < .0001). ConclusionThe study demonstrates that both long COVID and ME/CFS patients exhibit similarly impaired endothelial function, indicating potential vascular involvement in the pathogenesis of these post-viral illnesses. The significant reduction in flow-mediated dilation values suggests an increased cardiovascular risk in these populations, warranting careful monitoring and the development of targeted interventions to improve endothelial function and mitigate long-term health implications.

Kolekalsiferol sonrası endotel disfonksiyonu ve damar sertliğinin diyaliz modalitesine göre değerlendirilmesi

ABSTRACT&#x0D; Objective: The risk of developing cardiovascular disease (CVD) increases significantly in children with chronic kidney disease (CKD) especially with low serum 25- hydroxyvitamin D (25OHD) levels. Herein; we aimed to compare the effects of vitamin D deficiency and the impact of cholecalciferol treatment on endothelial functions and vascular stiffness in children with CKD receiving hemodialysis (HD), peritoneal dialysis (PD) and non- dialysis(ND).&#x0D; Methods: 7 HD, 7 PD and 27 ND patient groups consisting of 41 children totally with low 25OHD levels were compared among each other in regards of biochemical parameters, flow-mediated dilatation(FMD) and local arterial stiffness before and after a single dose of 300.000 units of cholecalciferol treatment.&#x0D; Results: There was no difference in FMD and local arterial stiffness values between HD, PD and ND patient groups before vitamin D supplementation. Significant increase in endothelium-dependent FMD was observed in all patient groups after intervention with cholecalciferol; however the improvement in endothelium-independent FMD and local arterial stiffness measurements was demonstrated in patients with PD and ND. Baseline parathormon level was higher in patients on dialysis; at the end of the study, significant decrease was detected only in patient group not receiving diaysis.&#x0D; Conclusions: Endothelial dysfunction and impaired vascular stiffness were determined in children with CKD with low 25OHD levels regardless of the disease severity.. Recovery with cholecalciferol therapy revealed that vitamin D deficiency should be corrected even in early stages of CKD to prevent the development of CVD

P-336 Presence of stage III/IV endometriosis associated with systemic inflammation poses as individual risk factor for coronary heart disease in Indian women: Inklings for the search

Abstract Study question Can investigating endometriosis—cardiovascular interaction identify women with stage III/IV endometriosis and elucidate pathophysiology of the female heart at a broader level? Summary answer Endothelial dysfunction can occur in absence of structural atherosclerotic changes in young Indian women with endometriosis urging lifelong multidisciplinary care to manage long-term health impact. What is known already Chronic inflammation, enhanced oxidative stress, endothelial dysfunction, and cellular proliferation are hallmarks of both atherosclerosis and endometriosis with unveiled cellular and molecular overlaps between the duos. Further, treatment/s of endometriosis, like, hysterectomy or oophorectomy and/or analgesics confer increased risk of coronary heart disease (CHD) to women with endometriosis. However, CHD in women with endometriosis remains understudied, under-recognized, and underdiagnosed. Incidentally, early atherosclerosis cannot be explained exclusively by traditional cardiovascular risk factors. Aim of the present study was to correlate subclinical atherosclerosis with metabolic parameters and markers of endothelial inflammation in Indian women with stage III/IV endometriosis. Study design, size, duration This observational prospective cohort study constituted 1407 consented women diagnosed with laparoscopically confirmed endometriosis (Group A; n = 718) with age matched control (Group B; n = 689) (counterpart/s of male infertility) from October 2021 to September 2022. Sub-clinical atherosclerosis was investigated before laparoscopy by ultrasound evaluation of carotid intima-media thickness (cIMT) and flow-mediated dilation (FMD). Serum samples were stored at -80 °C for evaluation of biochemical and inflammatory parameters. European Society of Cardiology guidelines were followed for standard definition/s. Participants/materials, setting, methods Traditional (obesity, hypertension) and metabolic (dyslipidaemia, diabetes, hyperhomocysteinemia) cardiovascular risk factor/s were assessed during evaluation and chemiluminescence respectively. Serum levels of interleukin (IL)-6, IL-8, IL-10, TNF-a, VEGF, and VCAM-1 were determined by enzyme-linked-immunosorbent assay/s. Univariate comparisons and bivariate correlations were conducted by Student’s t-test, and Spearman correlation respectively. Adjusted relative risks (aRR) with 95% confidence intervals (CI) were calculated by Cox-proportional hazard/s model among Group A vs Group B. Statistical significance was set at p &amp;lt; 0.05. Main results and the role of chance 62.95% and 37.04% women had stage III and stage IV endometriosis respectively as defined according to European Society for Human Reproduction and Embryology 2014 guideline. aRR (adjusted for demographic, obesity, diabetes mellitus, reproductive history, and migraine), documented a higher risk of hypertension (aRR 1.43; 95%CI 1.33–1.54) in women with endometriosis. On stratification of group A in less than and more than 40 years, laboratory parameters were similar except for significantly higher (p &amp;lt; 0.01) serum values of homocysteine, low density lipoprotein and cholesterol, in both age range of group A. FMD, indirect marker of endothelial dysfunction, was found to be lower in group A compared to controls (mean difference: −7.54, 95% CI: -10.32− -4.73; p&amp;lt; 0.001, however, cIMT was similar between both cohort/s. aRR of endometriosis in relation with hypercholesterolemia (1.07; 95%CI 1.01–1.25; p &amp;lt; 0.001), hypertension (1.22; 95%CI 1.14–1.30; p &amp;lt; 0.001), and hyperhomocysteinemia (1.04; 95%CI 0.96–1.12; p &amp;lt; 0.08) decreased with increasing age (&amp;gt;40 years). Systemic inflammation markers, showed an inverse relationship (p &amp;lt; 0.001) between values of FMD and serum levels of IL-6 (r = –0.34), TNF-a (r = –0.85), and VCAM-1 (r = –0.28) in group A. Other correlations were not statistically significant. Limitations, reasons for caution This observational study is not supported by patients with typical cardiovascular risk factors and hence limits generalizability of evidence to other ethnicities. Further, no information on hormonal treatments, such as dianogest (a synthetic progesterone) and/or leuprolide (gonadotropin-releasing hormone analog) are available to assess extent of association between endometriosis and CHD. Wider implications of the findings Higher propensity of subclinical atherosclerosis in younger women with laparoscopically-confirmed endometriosis represent higher systemic inflammation cueing to increased risk for CHD. This suggests the need for risk awareness and subsequent screening for CHD and healthy lifestyle promotion among gynaecologist/s and public health specialists. Trial registration number Not applicable

Impaired endothelial glycocalyx, vascular dysfunction and myocardial deformation four months after Covid-19 infection are partially improved at twelve months

Abstract Funding Acknowledgements Type of funding sources: None. Introduction COVID-19 patients present impaired subclinical markers of cardiovascular and endothelial function. Subclinical myocardial and vascular dysfunction during COVID-19 disease have been associated with worse outcomes and higher mortality risk. Purpose We investigated the effect of COVID-19 infection on markers of endothelial, vascular and myocardial function at four and twelve months after the infection Methods We recruited 70 patients who were examined in a dedicated post-COVID-19 outpatient clinic during a scheduled follow-up visit at four and twelve months after a confirmed COVID-19 infection and 70 healthy individuals with similar clinical characteristics. At four and twelve months we measured (i) perfused boundary region (PBR) of the sublingual arterial microvessels (increased PBR indicates reduced endothelial glycocalyx thickness), (ii) flow-mediated dilatation (FMD), (iii) coronary flow reserve (CFR) by Doppler echocardiography, (iv) pulse wave velocity (PWV) and central systolic blood pressure (cSBP), (v) global left and right ventricular longitudinal strain (GLS), (vi) myocardial global work index (GWI) global constructive work (GCW), global wasted work (GWW) and the myocardial global work efficiency (GWE) and v) malondialdehyde (MDA), an oxidative stress marker. Results At four months, COVID-19 patients displayed higher values of PBR5–25 compared to control group (p&amp;lt;0.001) which increased at twelve months (p&amp;lt;0.001). FMD, PWV and cSBP values were similar between 4 and 12 months (p&amp;gt;0.05 for all the comparisons) and higher than those in controls (p&amp;lt;0.001, p = 0.057, p = 0.003 respectively). At four months, COVID-19 patients presented impaired CFR and LVGLS values which were improved at twelve months (p = 0.002, p = 0.069 respectively), though remained impaired compared to controls (p = 0.003 for all the comparisons). At four months, COVID-19 patients had impaired RVGLS values which were significantly improved at twelve months (p = 0.001) and showed no statistically significant difference compared to controls (p&amp;gt;0.05). COVID-19 patients at four months display higher myocardial wasted work and decreased myocardial efficiency compared to controls (p = 0.01, p = 0.006, respectively). There was a modest improvement in GWW and GWE at twelve months, (p = 0.043, p = 0.001, respectively); however, these markers remained impaired compared to controls (p&amp;gt;0.05). At four months, MDA was higher in COVID-19 patients compared to control group and significantly decreased at twelve months (p&amp;lt;0.001); however, these values remain higher than in controls (p = 0.002). Conclusions SARS-CoV-2 causes endothelial and cardiovascular dysfunction which are partially restored at twelve months after the infection.

ASSESSMENT OF ENDOTHELIAL FUNCTION BY FLOW-MEDIATED DILATION IN WELL-CONTROLLED PATIENTS WITH RHEUMATOID ARTHRITIS

Objective: Endothelial dysfunction is considered as the primary pathophysiological process towards the development of cardiovascular disease (CVD). Patients with rheumatoid arthritis (RA) are at increased CVD risk attributed to the synergistic effect of chronic inflammation and traditional cardiovascular risk factors. However, it is uncertain whether endothelial function in RA is impaired even in the absence of cardiovascular comorbidities and pronounced inflammatory load. Design and method: Patients with RA who presented low levels of systemic inflammation and were free from cardiovascular comorbidities including hypertension, diabetes mellitus and established CVD, were studied. Non-RA individuals matched for age, sex and office systolic/diastolic blood pressure comprised the control group. Endothelial function was evaluated with the gold-standard flow-mediated dilation (FMD) in the brachial artery (Aloka ProSound A7 Ultrasound System). Results: A total of 22 female individuals were included in the study, of whom 10 were RA patients aged 57±13 years and 12 healthy volunteers aged 56±9 years. All patients with RA were at remission or low disease activity. Traditional CVD risk factors (age, systolic and diastolic blood pressure, smoking, body mass index and lipids) did not significantly differ between RA patients and controls. By contrast, significantly lower FMD values were observed in the RA group compared to controls [6.4 (5.0) vs 11.8 (5.2) %, p = 0.003]. The association between RA and FMD levels remained significant even after adjustment for age and systolic blood pressure (beta = 0.562, p = 0.009). Conclusions: Endothelial dysfunction is present in RA, even in a population characterized by the absence of hypertension and cardiovascular comorbidities and with relatively low systemic inflammatory burden. Further studies are warranted to verify the findings of this pilot study and delineate the role of endothelial dysfunction as a potential prognostic marker or therapeutic target.

Brachial artery flow-mediated dilation in patients with systemic sclerosis: an experience from tertiary care center from North India.

Role of flow-mediated dilatation (FMD) testing in the assessment of the macrovascular dysfunction in systemic sclerosis (SS) and correlation of FMD values with disease severity. Twenty-five patients of SS and 25 healthy age-matched controls were recruited. Modified Rodnan skin thickness score (MRSS) was used for skin thickness assessment. FMD values were measured in the brachial artery. FMD values done at baseline before the initiation of treatment were lower in SSc patients (4.044 ± 2.742) compared to the healthy controls (11.076 ± 5.896) (P < 0.05). Comparison of FMD values between patients with limited cutaneous systemic sclerosis (LSSc) and diffuse cutaneous systemic sclerosis (DSSc) showed a trend toward lower in LSSc (3.182 ± 2.482) as compared to DSSc patients (5.111 ± 2.711); however, the difference was not statistically significant. Patients with lung manifestations on high-resolution CT chest showed lower FMD values (2.66 ± 2.23) compared to those without HRCT changes (6.45 ± 2.56) (P < 0.05). We demonstrate that FMD values in SSc patients were lower when compared to healthy controls. Patients with SS having pulmonary manifestations showed a lower value of FMD. Key Points • FMD is a simple non-invasive tool to assess the endothelial function in patients with systemic sclerosis. • Lower values of FMD in systemic sclerosis suggest that the endothelial dysfunction and values can also be correlated with other organ involvement such as lung and skin involvement. So, lower FMD values might be a useful marker for disease severity.

The impact of statin therapy on in-hospital prognosis and endothelial function of patients at high-to-very high cardiovascular risk admitted for COVID-19.

Statins may protect against adverse outcomes from Coronavirus disease 2019 (COVID-19) through their pleiotropic effects. Endothelial dysfunction seems to be implicated in the pathophysiology of COVID-19, and can be attenuated by statins. This study assessed the role of preadmission statin therapy and its interaction with endothelial function, measured using flow-mediated dilation (FMD) at hospital admission, in predicting in-hospital outcomes among patients with COVID-19 having high-to-very high cardiovascular (CV) risk. We conducted a retrospective cohort study of hospitalized patients with COVID-19 having high-to-very high CV risk, including a subgroup of patients who underwent FMD assessment. Among 342 patients, 119 (35%) were treated with statins at study baseline. Preadmission statin therapy was independently associated with a 75% risk reduction of intensive care unit admission/in-hospital death (adjusted hazard ratio 0.252, 95% confidence interval 0.122-0.521, p < 0.001). In the subgroup of patients with an FMD assessment (245 patients, 40% statin-treated), preadmission statin therapy was independently associated with higher FMD values (β = 0.159, p = 0.013). However, preadmission statin therapy × FMD interaction was not associated with in-hospital outcomes (F = 0.002, pinteraction = 0.960). Preadmission statin therapy is associated with better in-hospital outcomes among patients with COVID-19 having high-to-very high CV risk, independent of the endothelium-protective effects of these drugs.

Abstract P407: Sex Differences in Microvascular Response to Mental Stress and Adverse Cardiovascular Events Among Patients With Ischemic Heart Disease

Introduction: Microvascular dysfunction during acute mental stress may be an important determinant of major adverse cardiovascular outcomes (MACE) especially among middle-aged women survivors of an acute myocardial infarction (MI). Hypothesis: There are sex differences in the association between microvascular dysfunction and MACE. Methods: The Myocardial Infarction and Mental Stress Study 2 enrolled individuals who had been hospitalized for an MI in the past 8 months at the age of 60 years or younger, with an oversampling of women. Reactive hyperemia index (RHI) was used to measure digital microvascular function before and 30 minutes after a public-speaking mental stress task. This assessment was contrasted with macrovascular endothelial function at the brachial artery through flow-mediated dilation (FMD). Participants were followed for 5-years, and MACE was defined as a composite of cardiovascular death, first/recurring events for nonfatal MI, and hospitalizations for heart failure. Cox proportional hazards models were used to examine vascular response to stress (difference between post-stress and resting values) and MACE adjusting for demographics, clinical risk factors, medications, psychological factors, and mental stress ischemia. Lower RHI and FMD values are indicative of greater microvascular and endothelial dysfunction, respectively. Results: Of 263 participants, the mean age was 51 years and 48% were women. There were 64 patients with 141 adverse cardiovascular events (first and repeated). In the overall sample, there was no significant association between microvascular response to stress and MACE, but there was a significant interaction with sex (p = 0.03). Each standard deviation decrease in RHI response to stress was associated with 50% greater risk of MACE (HR: 1.50, 95% CI: 1.05, 2.13) among women only, while no association was observed in men (HR 0.93, 95% CI: 0.69, 1.26). Transient endothelial dysfunction in response to stress (for each standard deviation decrease in FMD) was associated with 35% greater risk of MACE (HR: 1.35; 95% CI: 1.07, 1.71), and was similar in women and men. Conclusions: Peripheral microvascular dysfunction with mental stress is associated with MACE among women but not among men. In contrast, brachial artery endothelial dysfunction is similarly related to MACE among both men and women. These results suggest that microvascular dysfunction is a female-specific mechanism linking psychological stress to adverse outcomes.

PS-BPC02-3: EVALUATION OF VASCULAR FUNCTION FOR PREDICTION OF RENAL PROGNOSIS IN JAPANESE PATIENTS WITH LIFESTYLE-RELATED DISEASES.

Background: Since chronic kidney disease (CKD) is associated with the development of serious cardiovascular diseases such as stroke, coronary artery disease and heart failure, prevention and early diagnosis of CKD are important clinical issues. Many risk factors including diabetes, hypertension, dyslipidemia, obesity, and cigarette smoking are known to be involved in the development of CKD; however, there is no available biomarker that can predict the progression of CKD at an early stage. Although it has been reported that glomerular endothelial injury causes development of CKD, it remains unclear whether evaluation of vascular endothelial function can predict renal prognosis. Therefore, in the present study, we examined the association between vascular endothelial function and longitudinal eGFR change in patients with lifestyle-related diseases. Methods: We retrospectively evaluated 341 Japanese patients (176 males and 165 females; mean age, 63.87 ± 12.02 years) with lifestyle-related diseases in whom baseline vascular function was evaluated by flow-mediated dilation (FMD) and brachial-ankle pulse wave velocity (baPWV) and in whom 24-month longitudinal eGFR values were recorded after vascular testing at Tokushima University Hospital and Anan Medical Center, Tokushima Japan. The association between values of FMD and eGFR slope and the association between values of baPWV and eGFR slope were statistically analyzed. Statistical significance was set at p &lt; 0.05. Results: Single regression analysis showed that value of FMD was positively associated with eGFR slope in females (p &lt; 0.001) and non-smoking males (p = 0.033) but not in smoking males (p = 0.133). Multiple regression analysis including confounding factors demonstrated that the value of FMD remained a contributor against annual eGFR decline in females (p = 0.002) and non-smoking males (p = 0.046) but not in smoking males (p = 0.266). On the other hand, the value of baPWV had no significant association with eGFR slope regardless of sex and smoking. Conclusions: In patients with lifestyle-related diseases, FMD value can be used for prediction of renal prognosis represented by the eGFR slope in females and non-smoking males. Thus, early comprehensive intervention for improving vascular endothelial function might lead to a better renal prognosis in female and non-smoking male patients with lifestyle-related diseases.

Improvement in endothelial function in hypertensive patients after Ramadan fasting: effects of cortisol.

There are studies on the effects of Ramadan fasting (RF), which is one of the intermittent fasting diets, on both hypertension and endothelial function. However, the relationship between possible improvements in endothelial function and blood pressure after RF is not clear. In this study, we aimed to evaluate the effects of RF on blood pressure and endothelial dysfunction in patients with arterial hypertension (HT). : Sixty-four HT patients, aged 45-65, who were followed up in the Cardiology Department of Kayseri City Hospital and fasted during Ramadan between 13 April and 13 May 2021 with their self-consents were enrolled to study. Body mass index (BMI), blood pressure, and flow-mediated dilatation (FMD) were assessed before and after Ramadan. Also, 5 mL venous blood samples were taken between 8:00 and 8:30 a.m. from all participants to assess cortisol, C-reactive protein (CRP), and other laboratory data. : In patients, FMD values were found to be higher after Ramadan compared to values before the fasting period (p < 0.001). CRPand cortisol levels decreased after fasting, and the decrease in CRP (95% CI for B = -1.685 - -0.334, p = 0.009) and cortisol levels (95% CI for B = -0.392 - 0.092, p = 0.039) were determined as the predictive factors for FMD after RF. Endothelial functions as determined by FMD improved after 30 days of intermittent fasting. The decreased CRP and cortisol levels may contribute to the improvement in FMD after RF.