Antecubital venous endothelial ETB receptor protein expression is preserved with aging in men.

Changes in endothelial function precede the development of cardiovascular disease (CVD). We have previously shown that age-related declines in endothelial function in women are due in part to a reduction in endothelial cell endothelin-B receptor (ETBR) protein expression. However, it is not known if ETBR protein expression changes with aging in men. The purpose of this study was to test the hypothesis that ETBR protein expression is attenuated in older men (OM) compared with younger men (YM). Primary endothelial cells were harvested from the antecubital vein of 14 OM (60 ± 6 yr; 26 ± 3 kg/m2) and 17 YM (24 ± 5 yr; 24 ± 2 kg/m2). Cells were stained with 4',6-diamidino-2-phenylindole, vascular endothelial cadherin, and ETBR. Images were quantified using immunocytochemistry. Endothelial function was assessed using brachial artery flow-mediated dilation (FMD). Systolic BP was similar (OM, 123 ± 11 vs. YM, 122 ± 10 mmHg) whereas diastolic BP was higher in OM (OM, 77 ± 7 vs. YM, 70 ± 6 mmHg; P < 0.01). Total testosterone was lower in OM (OM, 6.28 ± 4.21 vs. YM, 9.10 ± 2.68 ng/mL; P = 0.03). As expected, FMD was lower in OM (OM, 3.85 ± 1.51 vs. YM, 6.40 ± 2.68%; P < 0.01). However, ETBR protein expression was similar between OM and YM (OM, 0.39 ± 0.17 vs. YM, 0.42 ± 0.17 AU; P = 0.66). These data suggest that ETBR protein expression is not altered with age in men. These findings contrast with our previous data in women and further support sex differences in the endothelin system.NEW & NOTEWORTHY Our laboratory has previously shown that age-related declines in endothelial function are associated with a reduction in endothelial cell ETBR protein expression in women. However, it is unclear if endothelial cell ETBR protein expression is reduced with aging in men. This study demonstrates that endothelial cell ETBR protein expression is preserved with aging in men, and provides additional evidence for sex differences in the endothelin system.

Vascular adaptation to exercise: a systematic review and audit of female representation.

Biological sex is a salient factor in exercise-induced vascular adaptation. Although a male bias is apparent in the literature, the methodological quality of available studies in females is not yet known. This systematic review with narrative synthesis aimed to assess available evidence of exercise interventions on endothelial function, measured using flow-mediated dilation, in otherwise healthy individuals and athletes. A standardized audit framework was applied to quantify the representation of female participants. Using a tiered grading system, studies that met best-practice recommendations for conducting physiological research in females were identified. A total of 210 studies in 5,997 participants were included, with 18% classified as athletes. The primary exercise mode and duration were aerobic (49%) and acute (61%), respectively. Despite 53% of studies (n = 111) including at least one female, female participants accounted for only 39% of the total study population but 49% of the athlete population. Majority (49%) of studies in females were conducted in premenopausal participants. No studies in naturally menstruating, hormonal contraceptive-users or in participants experiencing menstrual irregularities met all best-practice recommendations. Very few studies (∼5%) achieved best-practice methodological guidelines for studying females and those that did were limited to menopause and pregnant cohorts. In addition to the underrepresentation of female participants in exercise-induced vascular adaptation research, there remains insufficient high-quality evidence with acceptable methodological control of ovarian hormones. To improve the overall methodological quality of evidence, adequate detail regarding menstrual status should be prioritized when including females in vascular and exercise research contexts.

Remote and local effects of ischemic preconditioning on vascular function: a case for cumulative benefit.

Brief, repeated cycles of limb ischemia and reperfusion [ischemic preconditioning (IPC)] can protect against vascular insult. Few papers have considered the effect of IPC on resting vascular function, and no single study has simultaneously considered the local (trained arm) and remote (untrained arm) effects of a single session of IPC and following repeated sessions. We determined macrovascular [allometrically scaled flow-mediated dilation (FMD)] and microvascular [cutaneous vascular conductance (CVC)] function in healthy adults before, immediately post, 20 min post, and 24 h post a single session of IPC (4 × 5 min of single arm ischemia). These outcomes also were remeasured 24 h after six IPC sessions, performed over 2 wk. FMD and CVC increased in both arms 20 min post [FMD mean difference (MD) 1.1%, P < 0.001; CVC MD 0.08 arbitrary units (AU), P = 0.004] but not 24 h post (FMD MD -0.2%, P = 0.459; CVC MD -0.02 AU, P = 0.526] a single session of IPC, with no differences between trained and untrained arms. Although FMD did not increase 24 h after one IPC session, it was elevated in both arms 24 h after the sixth session (MD 1.2%, P = 0.009). CVC was not altered in either arm 24 h after the last IPC session. These data indicate that the local and remote effects of IPC on vascular health may be equivalent and that the benefits to FMD may be greater with sustained training compared with a single IPC exposure.

Obesity does not alter vascular function and handgrip exercise hemodynamics in middle-aged patients with hypertension.

Lifestyle modification including exercise training is often the first line of defense in the treatment of obesity and hypertension (HTN), however, little is known regarding how these potentially compounding disease states impact vasodilatory and hemodynamic responses at baseline and exercise. Therefore, this study sought to compare the impact of obesity on vascular function and hemodynamics at baseline and during handgrip (HG) exercise among individuals with HTN. Non-obese (13M/7F, 56 ± 16 yr, 25 ± 4 kg/m2) and obese (17M/4F, 50 ± 7 yr, 35 ± 4 kg/m2) middle-aged individuals with HTN forwent antihypertensive medication use for ≥2 wk before assessment of vascular function by brachial artery flow-mediated dilation (FMD) and exercise hemodynamics during progressive HG exercise at 15-30-45% maximal voluntary contraction (MVC). FMD was not different between Non-Obese (4.1 ± 1.7%) and Obese (5.2 ± 1.9%, P = 0.11). Systolic blood pressure (SBP) was elevated by ∼15% during the supine baseline and during HG exercise in the obese group. The blood flow response to HG exercise at 30% and 45% MVC was ∼20% greater (P < 0.05) in the obese group but not different after normalizing for the higher, albeit, nonsignificant differences in workloads (MVC: obese: 24 ± 5 kg, non-obese: 21 ± 5 kg, P = 0.11). Vascular conductance and the brachial artery shear-induced vasodilatory response during HG were not different between groups (P > 0.05). Taken together, despite elevated SBP during HG exercise, obesity does not lead to additional impairments in vascular function and peripheral exercising hemodynamics in patients with HTN. Obesity may not be a contraindication when prescribing exercise for the treatment of HTN among middle-aged adults, however, the elevated SBP should be appropriately monitored.NEW & NOTEWORTHY This study examined vascular function and handgrip exercise hemodynamics in obese and nonobese individuals with hypertension. Obesity, when combined with hypertension, was neither associated with additional vascular function impairments at baseline nor peripheral hemodynamics and vasodilation during exercise compared with nonobese hypertension. Interestingly, systolic blood pressure and pulse pressure were greater in the obese group during supine baseline and exercise. These findings should not be ignored and may be particularly important for rehabilitation strategies.

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

BACKGROUND: In 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. METHODS: A 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. RESULTS: FMD 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. CONCLUSIONS: Higher 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 REGISTRATION: The 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.

The association of microvascular disease and endothelial dysfunction with vertebral trabecular bone mineral density : The MESA study.

Retinopathy and albuminuria are associated with hip fracture risk. We investigated whether these disorders and endothelial dysfunction (which underlies microvascular diseases) were associated with low trabecular bone density. No significant associations were found, suggesting that microvascular diseases are not related to fracture risk through low trabecular bone density. PURPOSE: Microvascular diseases of the eye, kidney, and brain are associated with endothelial dysfunction and increased hip fracture risk. To explore the basis for higher hip fracture risk, we comprehensively examined whether markers of microvascular disease and/or endothelial dysfunction are related to trabecular bone mineral density (BMD), a proximate risk factor for osteoporotic fractures. METHODS: Among 6814 participants in the Multi-Ethnic Study of Atherosclerosis study (MESA), we derived thoracic vertebral trabecular BMD from computed tomography of the chest and measured urine albumin to creatinine ratios (UACR), retinal arteriolar and venular widths, flow mediated dilation (FMD) of the brachial artery after 5 min of ischemia; and levels of five soluble endothelial adhesion markers (ICAM-1, VCAM-1, L-selectin, P-selectin, and E-selectin). Linear regression models were used to examine the association of trabecular BMD with markers of microvascular disease and with markers of endothelial dysfunction. RESULTS: We observed no significant associations of UACR, retinal arteriolar or venular widths, or FMD with BMD. We also observed no statistically significant association of spine trabecular BMD with levels of endothelial adhesion markers. Men and women had largely similar results. CONCLUSION: We conclude that there is little evidence to connect thoracic spine trabecular BMD to microvascular disorders or to endothelial dysfunction among multi-ethnic middle-aged and older adults. Other factors beyond trabecular BMD (e.g., bone quality or predisposition to falling) may be responsible for the associations of microvascular disease with osteoporotic fractures.

Sexual function scores are associated with arterial stiffness in postmenopausal women.

BACKGROUND: Female sexual dysfunction (FSD) has been suggested to be correlated with the burden of cardiovascular risk factors. AIM: We aimed to evaluate the possible association between functional indices of vascular function and FSD scores in apparently healthy postmenopausal women. METHODS: This cross-sectional study included 116 postmenopausal women who underwent assessment of endothelial function with measurement of flow-mediated dilation (FMD) of the branchial artery and arterial stiffness estimation with measurement of the carotid-femoral pulse wave velocity (PWV). We used the Greene Climacteric Scale to evaluate vasomotor symptomatology, the Female Sexual Function Index (FSFI) to evaluate FSD and the Beck Depression Inventory to evaluate mood disorder. Low sexual function was defined as an FSFI score <26.55. OUTCOMES: These included FSFI and low sexual function scores as well as measures of PWV and FMD. RESULTS: Sexual function scores were associated with measures of blood pressure (normal vs low sexual function; systolic blood pressure: 120.2 ± 15.0 mm Hg vs 113.4 ± 14.6 mm Hg; analysis of covariance P = .026; diastolic blood pressure: 75.9 ± 10.5 mm Hg vs 70.3 ± 9.9 mm Hg; analysis of covariance P = .012; both adjusted for age, body mass index, current smoking, and PWV). Systolic blood pressure, but not diastolic blood pressure, was associated with FSFI (B = 0.249, P = .041) and PWV (B = 0.392, P < .001). PWV measures were associated with FSFI (B = -0.291, P = .047) and pulse pressure (B = 0.355, P = .017). FMD measures were also associated with FSFI (B = 0.427, P = .033). All models were adjusted for age, body mass index, current smoking, insulin resistance, vasomotor symptomatology, and Beck Depression Inventory. CLINICAL IMPLICATIONS: Our findings demonstrate that lower scores of sexual function are associated with deteriorated vascular function mainly manifested as arterial stiffening, further contributing to systolic blood pressure changes. STRENGTHS AND LIMITATIONS: The strength of this study is the carefully selected healthy sample of postmenopausal women, with simultaneous assessment of climacteric symptomatology and mood disorders. The limitations include the small sample size, the cross-sectional design, and the recruitment of consecutive outpatients of a university menopause clinic. CONCLUSION: Longitudinal studies and interventions to improve FSD should further assess the clinical relevance of these findings.

Effect of 60-Min Single Bout of Resistance Exercise, Reformer Pilates, on Vascular Function Parameters in Older Adults: A Randomized Crossover Study.

INTRODUCTION: Aging leads to vascular endothelial dysfunction and muscle impairment. While resistance exercise improves muscular function, its acute effects on vascular function vary in the literature, with some studies reporting detrimental effects. These findings indicate the need for exercises that optimize muscle function without compromising vascular function. Reformer Pilates (RP) is a low-impact exercise involving an adjustable sliding platform. However, the acute effects of RP on vascular function among older adults remain unknown. Therefore, this study aimed to investigate the acute effects of RP on vascular function in older adults. METHODS: Overall, 17 participants (age: 65 ± 2.76 years, body mass index: 23.42 ± 3.68 kg/m2) were examined and assigned to control and RP conditions under a randomized crossover design. The RP condition involved a 3.5-5 omnibus perceived exertion scale with 19 exercise postures for 60 min. Brachial artery flow-mediated dilation (FMD), brachial-ankle pulse wave velocity (baPWV), and blood pressure were measured at baseline and 0, 10, 30, and 60 min after exercise. RESULTS: RP significantly improved FMD at all time points compared with that at baseline (p < 0.05). baPWV increased at 0 min post-RP but returned to baseline levels at other time points. Additionally, RP showed improved FMD at 0, 10, and 30 min compared with that in the control condition (p < 0.05). However, no significant differences were observed in blood pressure or mean arterial pressure in either condition. CONCLUSION: RP enhanced FMD and regulated blood pressure for approximately 60 min post-exercise, suggesting its suitability for older adults to enhance vascular function and control blood pressure during exercise. Nonetheless, longitudinal resistance training intervention studies are needed to validate these findings.

Effects of Metformin on CIMT and FMD in PCOS patients: a systematic review and meta-analysis.

BACKGROUND: This study aims to analyze the efficacy of metformin on carotid intima media thickness (CIMT) and flow-mediated dilation (FMD) for patients with polycystic ovary syndrome (PCOS). METHODS: A literature search of PubMed, Embase, and the Cochrane Library from inception to December 2023 was conducted. Then, after studies selection and data extraction, the mean difference (MD) with a 95% confidence interval (CI) was used to evaluate metformin efficacy in CIMT and FMD for PCOS patients. Heterogeneity was investigated through subgroup and sensitivity analysis. The protocol of our study has been registered in PROSPERO (CRD42024497239). RESULTS: A total of 12 studies with 248 patients were included. CIMT was lower in the endpoint group (after metformin) compared with the baseline group (before metformin) (MD = -0.11, 95% CI = -0.21 to -0.01, p = 0.04). FMD was higher in the endpoint group compared with the baseline group (MD = 3.25, 95% CI = 1.85 to 4.66, p < 0.01). No statistically significant difference was observed in nitroglycerin-mediated dilation (NMD) between the two groups (MD = 0.65, p = 0.51). Subgroup analysis showed that a relatively lower MD of CIMT in PCOS patients from Europe in the endpoint group compared with the baseline group (MD = -0.09, 95% CI = -0.14 to -0.04, p < 0.001). However, the MD in CIMT was not significantly different between the endpoint group and baseline group in PCOS patients from Asia (p = 0.270). CONCLUSION: Metformin may have a beneficial effect on CIMT and FMD, but not on NMD, suggesting that metformin may help reduce cardiovascular events in PCOS patients. Notably, the clinical efficacy of metformin can be influenced by regional differences and study types.

Effects of smoking cessation on endothelial function as assessed by flow-mediated total dilation.

BACKGROUND: In assessing the effects of smoking cessation on endothelial function, low-flow-mediated constriction (L-FMC) may provide complementary information to flow-mediated dilation (FMD). However, the value of flow-mediated total dilation (FMTD), an index that incorporates L-FMC into FMD, remains underreported. We aimed to evaluate the effect of smoking cessation on endothelial function, as assessed by FMD and FMTD, and clarify its associated clinical factors. METHODS: We enrolled 118 consecutive current smokers without previous coronary artery disease (72.9% were men; age: 59 ± 11 years) who underwent smoking cessation treatment. The clinical variables %FMD, %L-FMC, and %FMTD were examined before and 20 weeks after treatment initiation. A multivariate linear regression model was used to investigate the effects of smoking cessation on %FMD and %FMTD and the interaction between smoking cessation and baseline clinical variables. RESULTS: After 20 weeks, 85 smokers (69.4% were men; age: 59 ± 12 years) ceased smoking (abstainers), whereas 33 smokers (81.8% were men; age: 58 ± 11 years) did not (continued smokers). The estimated group differences (abstainers - continued smokers) in changes in the %FMD and %FMTD were 0.77% (95% confidence interval [CI], -0.22-1.77%; p = 0.129) and 1.17% (95% CI, 0.16-2.18%; p = 0.024), respectively. Smoking cessation-associated improvement in %FMTD was greater in women than in men (5.41% [95% CI, 3.15-7.67%] versus 0.24% [95% CI, -0.81-1.28%]; p-value for interaction, < 0.001). Additionally, a greater %FMTD improvement was observed in patients who smoked fewer cigarettes per day (p-value for interaction, 0.042) and those who had a smaller resting baseline lumen diameter (Dbase) (p-value for interaction, 0.023). CONCLUSIONS: Smoking cessation was associated with an improvement in %FMTD. Sex, cigarettes smoked per day, and Dbase significantly affected this improvement. The FMTD may help in risk stratification after smoking cessation.

Effect of Hemodialysis with Medium Cut-Off versus High-Flux Membranes on Endothelial Function of Patients with Chronic Kidney Disease.

INTRODUCTION: Endothelial dysfunction (ED) is considered a marker of vascular complications, especially in patients with end-stage kidney disease (ESKD). Inflammation and the uremic state contribute to ED in patients undergoing hemodialysis (HD). Recently, the medium cut-off (MCO) dialysis membrane has been proposed to efficiently remove inflammatory cytokines and large, middle-sized uremic toxins, with the potential effect to improve endothelial function. This study aimed to compare the effect of dialysis with MCO or high-flux membranes on the endothelial function of patients on chronic HD. METHODS: A prospective, randomized, crossover study in which 32 patients with ESKD were dialyzed for 12 weeks with each membrane, including a 4-week washout period between treatments. Endothelial function was assessed by flow-mediated dilation (FMD) using brachial artery ultrasound at weeks 1, 12, 16, and 28. RESULTS: The population consisted of 59% men, 52.7 ± 13.4 years, 16% non-black, on HD for 8.8 (4.1-15.1) years, and 72% with arteriovenous fistula. Hypertension was the most common etiology of chronic kidney disease, and 34% of patients had previous cardiovascular disease. Patients were grouped, regardless of treatment sequence, into MCO or high-flux groups, since no carryover (p = 0.634) or sequence (p = 0.998) effects were observed in the FMD assessment. The ANOVA model with repeated measures showed no effects of treatment (p = 0.426), time (p = 0.972), or interaction (p = 0.413) in the comparison of FMD between the MCO and high-flux groups. CONCLUSION: Dialysis performed with MCO, or high-flux membranes, had no influence on endothelial function in patients undergoing HD. However, a trend towards increased FMD was observed with the use of the MCO membrane.

Variability of flow-mediated dilation across lower and upper limb conduit arteries.

Endothelial dysfunction is an early predictor of atherosclerosis and cardiovascular disease. Flow-mediated dilation (FMD) is the gold standard to assess endothelial function in humans. FMD reproducibility has been mainly assessed in the brachial artery (BA) with limited research in lower limb arteries. The purpose of this study was to compare FMD reproducibility in the upper limb BA and lower limb superficial femoral artery (SFA) in young healthy adults.Fifteen young healthy adults (nine males; six females) underwent FMD, resting diameter, velocity, and shear rate measurements on three occasions to determine intra-and inter-day reproducibility in both BA and SFA, assessed by coefficient of variation (CV), intraclass correlation coefficient (ICC), and Bland-Altman plots.BA FMD CVs (intra-day: 4.2%; inter-day: 8.7%) and ICCs (intra-day: 0.967; inter-day: 0.903) indicated excellent reproducibility and reliability, while for SFA FMD, both CVs (intra-day: 11.6%; inter-day: 26.7%) and ICCs (intra-day: 0.898; inter-day: 0.651) showed good/moderate reproducibility and reliability. BA FMD was significantly more reproducible than SFA FMD (p < 0.05). Diameter reproducibility was excellent and similar between arteries, while resting velocity and shear rate have lower reproducibility in the BA compared to SFA. Bland-Altman plots displayed no proportional and fixed bias between measurements.In summary, SFA FMD is less reproducible than BA FMD, with identical volume of ultrasound training. Given the increasing interest in using SFA FMD to test the efficacy of interventions targeting lower limb's vascular health and as a potential biomarker for peripheral arterial disease risk, future studies should ensure higher levels of training for adequate reproducibility.

Effect of low-volume combined aerobic and resistance high-intensity interval training on vascular health in people with type 2 diabetes: a randomised controlled trial.

PURPOSE: We compared the effects of low-volume combined aerobic and resistance high-intensity interval training (C-HIIT), combined moderate-intensity continuous training (C-MICT) and waitlist control (CON) on vascular health after 8-weeks of supervised training, and an additional 10-months of self-directed training, in adults with type 2 diabetes (T2D). METHODS: Sixty-nine low active adults with T2D were randomised to 8-weeks of supervised C-HIIT (3 times/week, 78-min/week), C-MICT (current exercise guidelines, 4 times/week, 210-min/week) or CON. CON underwent usual care for 8-weeks before being re-randomised to C-HIIT or C-MICT. This was followed by 10-months of self-directed training for participants in C-HIIT and C-MICT. Vascular outcomes were evaluated at baseline, 8-weeks, and 12-months. RESULTS: After 8-weeks, supervised C-HIIT significantly improved relative flow-mediated dilation (FMD) compared with CON (mean difference [MD] 0.8% [0.1, 1.4], p = 0.025). Although not significantly different from CON, the magnitude of change in relative FMD following 8-weeks of supervised C-MICT was similar (MD 0.8% [-0.1, 1.7], p = 0.080). There were no differences in haemodynamic indices, carotid-femoral pulse wave velocity (cfPWV), or aortic reservoir pressure between groups at 8-weeks. After 12-months, there was a significant reduction in haemodynamic indices (time effect, p < 0.05) for both C-HIIT and C-MICT, with no between-group difference. The reduction in cfPWV over 12-months was significantly greater in C-MICT than C-HIIT (group × time effect, p = 0.018). There was no difference in FMD over time or between groups at 12-months. CONCLUSIONS: Short-term supervised C-HIIT and C-MICT both increased brachial artery FMD compared with CON. Long-term C-HIIT and C-MICT were beneficial for improving haemodynamic indices, but not brachial artery FMD. C-MICT was superior to C-HIIT for improving cfPWV at 12-months. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry Identifier ACTRN12615000475549.

Combined peripheral and central ultrasound for the diagnosis of PAH-SSc patients.

BACKGROUND: Systemic Sclerosis (SSc), an intricate autoimmune disease causing tissue fibrosis, introduces cardiovascular complexities, notably pulmonary hypertension (PH), affecting both survival and quality of life. This study centers on evaluating echocardiographic parameters and endothelial function using flow-mediated dilatation (FMD) in SSc patients, aiming to differentiate those with and without pulmonary arterial hypertension (PAH). The emphasis lies in early detection, given the heightened vulnerability of the right ventricle (RV) in the presence of PH. METHODS: Fifty-nine SSc patients and 48 healthy subjects participated, undergoing clinical examinations, echocardiography, FMD assessments, blood analyses, and right heart catheterization (RHC) according to the ESC/ERS guidelines for diagnosis and treatment of PH. RESULTS: SSc-PAH patients displayed lower FMD, higher frequency of TAPSE < 18 mm, RA area > 18 cm2, act RVOT < 105 ms and TRV > 280 cm/s compared to those without PAH and healthy controls. Resting resistivity index (RI) was higher in SSc patients, with no significant difference between those with and without PAH. Lower FMD% serves as a predictive marker for adverse cardiovascular outcomes in both SSc and SSc-PAH patients. Stratification by TRV levels and PAH presence reveals notable FMD% variations, emphasizing its potential utility. CONCLUSIONS: Early identification of endothelial dysfunction and impaired RV echocardiographic parameters, such as TAPSE and TRV, could aid in predicting right ventricular dysfunction and PAH in SSc patients.

Effect of walnut consumption on markers of endothelial function in adults: A systematic review and meta-analysis of randomized controlled trials.

Findings on the effect of walnut consumption on endothelial function are conflicting. Therefore, the present systematic review and meta-analysis summarized available trials in this regard. A systematic search was performed in online databases including PubMed-Medline, Scopus, and ISI Web of Science up to October 2023. Articles that reported the effect of walnut intake on flow-mediated dilation (FMD), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and stimulus-adjusted response measure (SARM) were included. Random effects models for a weighted mean difference (WMD) or standardized mean difference (SMD) were used to test for the overall effect. Six eligible trials were analyzed (250 participants). Walnut intake significantly increased FMD (WMD: 0.94%, 95% CI: 0.12 to 1.75; p = 0.02). However, meta-analysis could not show any beneficial effect of walnut intake on ICAM-1 (SMD: -0.23, 95% CI: -0.68 to 0.22; p = 0.31), VCAM-1 (SMD: -0.02, 95% CI: -1.38 to 1.34; p = 0.97), and SARM (WMD: 0.01%, 95% CI: -0.01 to 0.04; p = 0.28). In conclusion, the present meta-analysis suggests that walnuts may reduce cardiovascular disease risk by improving FMD. However, further studies should be performed on adults to determine the effect of walnut intake on endothelial function.

Temporal Convolutional Neural Network-Based Prediction of Vascular Health in Elderly Women Using Photoplethysmography-Derived Pulse Wave during Exercise.

(1) Background: The objective of this study was to predict the vascular health status of elderly women during exercise using pulse wave data and Temporal Convolutional Neural Networks (TCN); (2) Methods: A total of 492 healthy elderly women aged 60-75 years were recruited for the study. The study utilized a cross-sectional design. Vascular endothelial function was assessed non-invasively using Flow-Mediated Dilation (FMD). Pulse wave characteristics were quantified using photoplethysmography (PPG) sensors, and motion-induced noise in the PPG signals was mitigated through the application of a recursive least squares (RLS) adaptive filtering algorithm. A fixed-load cycling exercise protocol was employed. A TCN was constructed to classify flow-mediated dilation (FMD) into "optimal", "impaired", and "at risk" levels; (3) Results: TCN achieved an average accuracy of 79.3%, 84.8%, and 83.2% in predicting FMD at the "optimal", "impaired", and "at risk" levels, respectively. The results of the analysis of variance (ANOVA) comparison demonstrated that the accuracy of the TCN in predicting FMD at the impaired and at-risk levels was significantly higher than that of Long Short-Term Memory (LSTM) networks and Random Forest algorithms; (4) Conclusions: The use of pulse wave data during exercise combined with the TCN for predicting the vascular health status of elderly women demonstrated high accuracy, particularly in predicting impaired and at-risk FMD levels. This indicates that the integration of exercise pulse wave data with TCN can serve as an effective tool for the assessment and monitoring of the vascular health of elderly women.

Flow-mediated Dilation of the Brachial Artery in Women with Hypertensive Disorders of Pregnancy.

Background: Hypertensive disorder of pregnancy (HDP) comprise chronic hypertension, gestational hypertension, preeclampsia/eclampsia, and preeclampsia superimposed on chronic hypertension. HDP complicate up to 10% of pregnancies worldwide and carry significant risks of maternal and perinatal morbidity and mortality. The aim of this study was to evaluate the derangement and characteristics of brachial artery flow-mediated dilation (BAFMD) in women with HDP. Methods: The BAFMD of the right brachial artery of 80 women with HDP (pregnant HDP), 80 normotensive pregnant women (pregnant non-HDP), and 80 healthy nonpregnant women (nonpregnant controls) was evaluated with B-mode ultrasound. The age, blood pressure, body mass index (BMI), brachial artery diameter, and BAFMD of the participants were compared. P ≤ 0.05 was statistically significant. Results: The pregnant HDP group had significantly lower mean BAFMD compared to pregnant non-HDP and nonpregnant controls (6.9% ± 2.53% vs. 8.32% ± 3.4% vs. 9.4% ± 2.68%; P < 0.001). There was no significant difference between the mean BAFMD of the pregnant HDP subgroups: preeclampsia (5.81% ± 1.7%) versus gestational hypertension (6.43% ± 3.02%); P = 0.57. BAFMD diminished with advancing gestational age in both the pregnant HDP and pregnant non-HDP groups. On regression analysis, BAFMD was a poor marker for HDP, while BMI was an independent predictor for HDP. Conclusion: Even though HDP were associated with significantly diminished BAFMD, it was not a good marker for HDP.

Neuraminidase inhibition improves endothelial function in diabetic mice.

Neuraminidases cleave sialic acids from glycocalyx structures and plasma neuraminidase activity is elevated in type 2 diabetes (T2D). Therefore, we hypothesize circulating neuraminidase degrades the endothelial glycocalyx and diminishes flow-mediated dilation (FMD), whereas its inhibition restores shear mechanosensation and endothelial function in T2D settings. We found that compared with controls, subjects with T2D have higher plasma neuraminidase activity, reduced plasma nitrite concentrations, and diminished FMD. Ex vivo and in vivo neuraminidase exposure diminished FMD and reduced endothelial glycocalyx presence in mouse arteries. In cultured endothelial cells, neuraminidase reduced glycocalyx coverage. Inhalation of the neuraminidase inhibitor, zanamivir, reduced plasma neuraminidase activity, enhanced endothelial glycocalyx length, and improved FMD in diabetic mice. In humans, a single-arm trial (NCT04867707) of zanamivir inhalation did not reduce plasma neuraminidase activity, improved glycocalyx length, or enhanced FMD. Although zanamivir plasma concentrations in mice reached 225.8 ± 22.0 ng/mL, in humans were only 40.0 ± 7.2 ng/mL. These results highlight the potential of neuraminidase inhibition for ameliorating endothelial dysfunction in T2D and suggest the current Food and Drug Administration-approved inhaled dosage of zanamivir is insufficient to achieve desired outcomes in humans.NEW & NOTEWORTHY This work identifies neuraminidase as a key mediator of endothelial dysfunction in type 2 diabetes that may serve as a biomarker for impaired endothelial function and predictive of development and progression of cardiovascular pathologies associated with type 2 diabetes (T2D). Data show that intervention with the neuraminidase inhibitor zanamivir at effective plasma concentrations may represent a novel pharmacological strategy for restoring the glycocalyx and ameliorating endothelial dysfunction.

Cardiovascular and cerebral vascular health in females with postacute sequelae of COVID-19.

Many individuals who had coronavirus disease 2019 (COVID-19) develop detrimental persistent symptoms, a condition known as postacute sequelae of COVID-19 (PASC). Despite the elevated risk of cardiovascular disease following COVID-19, limited studies have examined vascular function in PASC with equivocal results reported. Moreover, the role of PASC symptom burden on vascular health has not been examined. We tested the hypothesis that peripheral and cerebral vascular function would be blunted and central arterial stiffness would be elevated in patients with PASC compared with age-matched controls. Furthermore, we hypothesized that impairments in vascular health would be greater in those with higher PASC symptom burden. Resting blood pressure (BP; brachial and central), brachial artery flow-mediated dilation (FMD), forearm reactive hyperemia, carotid-femoral pulse wave velocity (PWV), and cerebral vasodilator function were measured in 12 females with PASC and 11 age-matched female controls without PASC. The severity of persistent symptoms in those with PASC was reported on a scale of 1-10 (higher score: greater severity). Brachial BP (e.g., systolic BP, 126 ± 19 vs.109 ± 8 mmHg; P = 0.010), central BP (P < 0.050), and PWV (7.1 ± 1.2 vs. 6.0 ± 0.8 m/s; P = 0.015) were higher in PASC group compared with controls. However, FMD, reactive hyperemia, and cerebral vasodilator function were not different between groups (P > 0.050 for all). Total symptom burden was not correlated with any measure of cardiovascular health (P > 0.050 for all). Collectively, these findings indicate that BP and central arterial stiffness are elevated in females with PASC, whereas peripheral and cerebral vascular function appear to be unaffected, effects that appear independent of symptom burden.NEW & NOTEWORTHY We demonstrate for the first time that resting blood pressure (BP) and central arterial stiffness are higher in females with PASC compared with controls. In contrast, peripheral and cerebral vascular functions appear unaffected. Moreover, there was no relationship between total PASC symptom burden and measures of BP, arterial stiffness, or vascular function. Collectively, these findings suggest that females with PASC could be at greater risk of developing hypertension, which appears independent of symptom burden.

Exploring heated exercise as a means of preventing the deleterious effects of high-sodium intake in Black women.

The purpose of this study was to examine whether hot yoga could attenuate sodium-induced pressor responses and endothelial dysfunction in Black females. Fourteen participants (ages 20-60 yr old) completed 3 days of low-sodium intake (≤31 mmol/day) followed by 3 days of high-sodium intake (201 mmol/day). Ambulatory blood pressure (BP), 24-h urinary sodium excretion, flow-mediated dilation (FMD), urine-specific gravity, and hematocrit were measured during/after each dietary phase. Participants were randomly assigned to 4 wk of hot yoga or a wait-list control condition. Wait-listed participants were rerandomized to the yoga group after week 4. Blood pressure and FMD in response to low- and high-sodium diet conditions were assessed again at week 4. Sodium loading significantly increased body mass, laboratory systolic and mean arterial BP and urinary sodium excretion in the group overall (P < 0.05 for all). A significant time-by-group interaction was observed for sodium-induced changes in FMD (P < 0.05). In the yoga group, sodium loading tended to decrease FMD at baseline (P = 0.054), whereas sodium loading significantly increased FMD after 4 wk of hot yoga (P < 0.05). In conclusion, results suggest that a brief heated exercise intervention can alter sodium's effects on endothelial function in Black female adults.NEW & NOTEWORTHY Hot yoga significantly altered endothelial function responses to high-sodium intake in Black female adults. Blood pressure responses were unaltered by the yoga intervention in this population.