Improvement In Flow-mediated Dilation Research Articles

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

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

The effect of exercise on flow-mediated dilation in people with type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials.

An increasing number of studies have investigated the effect of exercise on flow-mediated dilation (FMD) in people with type 2 diabetes mellitus (T2DM), while the findings were controversial. The primary aim of this systematic review and meta-analysis was to investigate the effect of exercise on FMD in T2DM patients, and the secondary aim was to investigate the optimal type, frequency, session duration, and weekly time of exercise for T2DM patients. Searches were conducted in PubMed, Cochrane Library, Scopus, Web of Science, Embase and EBSCO databases. The Cochrane risk of bias tool (RoB2) in randomized trial and Physiotherapy Evidence Database (PEDro) scale were used to assess the methodological quality of the included studies. From the 3636 search records initially retrieved, 13 studies met the inclusion criteria. Our meta-analysis revealed that exercise had a significant effect on improving FMD in T2DM patients [WMD, 2.18 (95% CI, 1.78-2.58), p < 0.00001, I2 = 38%], with high-intensity interval training (HIIT) being the most effective intervention type [HIIT, 2.62 (1.42-3.82); p < 0.0001; aerobic exercise, 2.20 (1.29-3.11), p < 0.00001; resistance exercise, 1.91 (0.01-3.82), p = 0.05; multicomponent training, 1.49 (0.15-2.83), p = 0.03]. In addition, a higher frequency [> 3 times, 3.06 (1.94-4.19), p < 0.00001; ≤ 3 times, 2.02 (1.59-2.45), p< 0.00001], a shorter session duration [< 60 min, 3.39 (2.07-4.71), p < 0.00001; ≥ 60 min, 1.86 (1.32-2.40), p < 0.00001], and a shorter weekly time [≤ 180 min, 2.40 (1.63-3.17), p < 0.00001; > 180 min, 2.11 (0.82-3.40), p = 0.001] were associated with larger improvements in FMD. This meta-analysis provides clinicians with evidence to recommended that T2DM patients participate in exercise, especially HIIT, more than 3 times per week for less than 60 min, with a target of 180 min per week being reached by increasing the frequency of exercise. https://www.crd.york.ac.uk/prospero, identifier CRD42023466575.

Statin Therapy and Flow-Mediated Dilation: A Systematic Review and Dose-Response Meta-Analysis Using the GRADE of Data from Randomized Controlled Trials.

A previous meta-analysis reported the positive effects of statin therapy on endothelial function. However, the obtained result had several limitations that necessitated updating the information in this field. Therefore, a systematic and meta-analysis review was conducted to determine whether statin therapy could improve endothelial function, as assessed by flow-- mediated dilation (FMD). MEDLINE, SciVerse Scopus, and Clarivate Analytics Web of Science were searched to identify randomized placebo-controlled trials assessing the impact of statin therapy on FMD. A random-effects model was used for meta-analysis to calculate the mean difference in weight. Meta- regression and subgroup analyses were used to identify sources of heterogeneity. In addition, nonlinear dose-response, quality of evidence, influence analysis, and publication bias evaluation were assessed using standard methods. Thirty-five trials (41 arms) involving 2178 participants were included in the meta-analysis study. Statin treatment significantly improved FMD [weighted mean difference (WMD): 1.7%, 95% CI: 1.3-2.2, p < 0.001). However, significant heterogeneity was observed (I2=97.9%, p < 0.001). The results of the subgroup analysis showed that health status can contribute to heterogeneity. Non-linear dose-response analysis revealed the most significant improvement in FMD with atorvastatin at a dose of 20 mg/day and simvastatin at 80 mg/day. Statin therapy significantly improved endothelial function, as assessed by FMD. These changes are clinically significant, but their use should be approached with caution.

Acute inspiratory resistance training enhances endothelium-dependent dilation and retrograde shear rate in healthy young adults.

Inspiratory resistance training (IRT) yields significant reductions in resting blood pressure and improves vascular endothelial function. Our objective was to quantify the acute effects of IRT on brachial artery flow-mediated dilation (FMD) and shear rates (SRs) in healthy men and women. Twenty young adults (22.9 ± 3.4 years; 10 male, 10 female) completed a single bout of IRT or Rest condition in a randomized crossover design. Brachial artery FMD was performed before, 10 min after, and 40 min after the assigned condition. Brachial artery blood flow velocities were collected during IRT, separated by breathing cycle phase, and converted into SRs. FMD improved 10 min post-IRT (+1.86 ± 0.61%; p = 0.025) but returned to baseline by 40 min post-IRT (p = 0.002). Anterograde SR decreased by 10% and retrograde SR increased 102% during resisted inspiration, relative to baseline SR (p < 0.001). Anterograde SR increased by 7% in men and women (p < 0.001) and retrograde SR decreased by 12% in women but not men (p = 0.022) during unresisted expiration, relative to baseline SR. A single bout of IRT elicits a transient enhancement in FMD in both men and women. Acute IRT-related enhancements in SRs may contribute to sustained improvements in FMD that have been reported previously.

Vascular effects and benefits through Helical stent implantation vs. conventional stenting: Methodology and initial Results of The MIMICS FLOW investigator-initiated randomized controlled trial

Abstract Aims Endovascular treatment is the primary revascularization strategy for symptomatic peripheral artery disease (PAD), which not only restores tissue perfusion but also affects local lower limb arterial endothelial function. Endothelial dysfunction is the pathophysiologic principle involved in the progression of atherosclerosis and is a prognostically relevant cardiovascular biomarker. A helical stent with a unique 3D helical geometry promotes laminar swirling blood flow elevating wall sheer stress, providing superior hemodynamic advantages and excellent clinical performance as compared to conventional stenting. The potential impact on endothelial homeostasis and the detailed mechanisms following a biomimetic or conventional stent are unknown. To this aim we now determined the effect of the Biomimics or a conventional stent on endothelial and vascular function in symptomatic PAD. Methods The MIMICS-FLOW is an investigator-initiated single-blind, randomized controlled trial (NCT05447052). The influence of novel stent-platforms with improved hemodynamic capabilities with respect to vasomotion of the vessel wall, vascular function and vascular compliance was measured by flow-mediated dilation (FMD) and arterial stiffness indices. Vascular function was determined in 70 PAD patients, Rutherford 2, 3 and 4 randomized to a helical stent and the conventional straight nitinol stent before and after lower limb intervention with a one-month follow-up in the nonstenotic segment of the proximal SFA. Perfusion indices, TLR rate and primary patency were assessed. Results The methodology and initial results regarding endothelial function after 1 month will be presented at ESC. In brief, 70 Patients aged 67 years were 1:1 randomized to each group prior to stent implantation in the SFA. Rutherford and PACSS class and target lesion locations were balanced between groups. One patient in the helical and 2 patients in the Straight group required a reintervention. A higher improvement in SFA FMD was observed in the helical group as compared to conventional stenting (p&amp;lt;0.05). Importantly, this effect was mirrored also by a greater increase in brachial FMD in the helical vs. conventional group (p&amp;lt;0.05). No impact was observed between groups regarding arterial or aortic stiffness. Conclusions Our RCT data provide evidence for an improved vascular function through swirling flow with superior hemodynamics following a helical stent implantation. These findings support the concept for a better mechanistic understanding to enhance endovascular treatment strategies in PAD.

Cardiovascular evaluation and endothelial dysfunction in Cushing syndrome following remission: a prospective study.

Cushing syndrome (CS) is a well-known risk factor for cardiovascular morbidities. We aimed to evaluate endothelial and cardiovascular functions, endothelial mediators and pro-inflammatory cytokines in patients with CS before and after remission. Adult patients with newly diagnosed endogenous CS were included. Metabolic [body mass index (BMI), glucose, and lipid values] and cardiovascular evaluation studies [24-h ambulatory blood pressure monitoring, carotid intima-media thickness (CIMT), flow-mediated dilation (FMD), and echocardiography] were performed, and endothelial mediators [asymmetric dimethyl arginine (ADMA) and endothelin-1 (ET-1)] and pro-inflammatory cytokines [interleukin-1β (IL-1β) and tumor necrosis factor-alpha (TNF-α)] were measured. Control group was matched in terms of age, gender, and BMIs. Twenty-five patients, mean age 40.60 ± 14.04years, completed the study. Compared to controls (n = 20) mean arterial pressure (MAP) and CIMT were higher (p < 0.005 and p = 0.012, respectively), and FMD (p < 0.001) and mitral E/A ratio (p = 0.007) lower in the patients during active disease. Baseline serum ADMA, ET-1, and IL-1β were similar between the groups, while TNF-α was lower in the patients (p = 0.030). All patients were in complete remission 1 year following surgery. BMI, LDL cholesterol, serum total cholesterol, fasting plasma glucose, MAPs, and CIMT significantly decreased (p < 0.005), while there was no improvement in FMD (p = 0.11) following remission. There was no significant change in ADMA, IL-1β, and TNF-α levels, but ET-1 increased (p = 0.011). Remission in CS improves some cardiovascular parameters. ADMA and ET-1 are not reliable markers for endothelial dysfunction in CS. Metabolic improvements may not directly reflect on serum concentrations of TNF-α and IL-1β following remission of CS.

Can yoga show better vascular outcomes than regular exercise among office workers: a scoping review

Background: Isolated systolic hypertension (ISH) in the elderly is mostly brought on by arterial stiffness with ageing, which results in a lack of vascular compliance. The main cardiovascular (CV) hazards for elderly persons are arterial ageing and high blood pressure (BP). The aim of this study was to investigate if endothelial function in young, middle-aged, and older, healthy persons would be improved by Bikram yoga, a heated form of hatha yoga. Methods: Randomised control trials on yoga, vascular function, exercise, and office employees were used in the study, which was done in four databases (Scopus, PubMed, Ovid, and Science Direct). Results: 3 of 103 articles were included. We identified improvement of vascular function, FMD and arterial stiffness using yoga intervention. While exercise does not significantly affect ventricular function, yoga significantly reduces heart rate (p = 0.031) and increases pulse pressure (PD). Yoga also results in a mean increase in left ventricular ejection time (LVET), which was observed in the yoga group. The improvement in myocardial function was more pronounced in the yoga group than in the exercise group, according to the between-group analysis, which revealed a significant difference in post-intervention rate-pressure product (RPP) between the yoga and exercise groups. With a P value of 0.004, the mean% Mean Arterial Pressure (MAP) was significantly lower, demonstrating that yoga was effective in lowering MAP. However, older adults, but not younger ones, experienced a significant increase in brachial artery FMD (Flow Mediated Dilation) following the intervention. Conclusions: Yoga interventions may improve vascular function, arterial stiffness, flow-mediated dilation, heart rate, RRP and MAP, with older adults experiencing a significant increase in brachial artery FMD, suggesting the effectiveness of yoga in improving myocardial function and lowering MAP, particularly in older adults.

Effect of endodontic treatment on endothelial dysfunction and subclinical atherosclerosis-a prospective intervention study.

The objective of this study is to investigate the effect of endodontic treatment on flow-mediated dilatation (FMD) and carotid intima-media thickness (c-IMT) in patients with apical periodontitis (AP). The study includes 32 young men having AP with a mean age of 25.78 years free from cardiovascular disease (CVD) and its risk factors, including periodontitis. All subjects underwent complete physical and dental examination, echocardiography, and ultrasound assessment of FMD on the brachial artery and c-IMT on the carotid artery at baseline and 12 months after the endodontic treatment. Data were analyzed using paired Student's t-test and Pearson's correlation coefficient (r) test using SPSS 26 version. Endodontic treatment leads to the improvement of FMD significantly from a pooled baseline value of 4.84 ± 1.55% to 7.68 ± 2.08% (p < 0.05). The study also depicts a statistically significant difference between c-IMT (mean = 0.62 ± 0.11 mm) before treatment as compared to 12 months after treatment (mean = 0.59 ± 0.11 mm) (p < 0.05). Endodontic treatment leads to improved FMD and decreased c-IMT suggesting that treating AP can be help revert the early stages of CVD. AP could be a potential etiological factor of future CVD and should be treated as soon as diagnosed.

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

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

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

Impact of Blood-Flow-Restricted Training on Arterial Functions and Angiogenesis-A Systematic Review with Meta-Analysis.

Despite growing evidence of the significant influence of blood-flow-restricted (BFR) training on different body functions, its impact on the vascular system, especially the arteries, is controversial. Therefore, the objective of our study was to analyze how BFR exercise, compared to other types of exercise without the restriction of blood flow, influences arterial functions and angiogenesis in adults. Studies comparing the effect of BFR versus non-BFR training on arterial parameters were divided into three categories: endothelial function, angiogenesis, and other vasculature functions. The search was based on Cochrane Library, PubMed®, and Embase, and 38 studies were included. The meta-analysis revealed a more significant improvement in flow-mediated dilatation (FMD) (p = 0.002) and the production of the primary angiogenesis biomarker vascular endothelial growth factor (VEGF) (p = 0.009) after BFR compared to non-BFR training (p = 0.002). The analysis of the pulse wave velocity, ankle-brachial index, systolic blood pressure, and heart rate did not show significant differences in changes between BFR and non-BFR training. The other parameters examined did not have sufficient data to be included in the meta-analysis. The results obtained present trends that suggest significant impacts of BFR training on endothelial functions and angiogenesis. There is still a lack of multicenter randomized clinical trials including many participants, and such studies are necessary to confirm the advantage of BFR over non-BFR activity.

Moderate continuous- and high-intensity interval training elicit comparable cardiovascular effect among middle-aged men regardless of recovery mode

ABSTRACT To assess the effect of active and passive intra-interval recovery modes in time-efficient high-intensity interval training (HIT) on cardiorespiratory fitness, autonomic function, and endothelial function in sedentary middle-aged men. Participants (n = 62; age: 49.5 ± 5.8 y; BMI: 29.7 ± 3.7 kg·m−2) completed the assessments of cardiorespiratory fitness, flow-mediated dilation (FMD) and heart rate variability before being randomly allocated to control (CON; n = 14), moderate intensity continuous training (MICT; n = 15), HIT with passive (P-HIT; n-15), or active recovery (A-HIT; n = 15). Participants performed thrice weekly exercise sessions for 12 weeks. MICT completed 50–60 min of continuous cycling at 60–70% heart rate (HR) maximum. HIT completed 30-s work intervals (∼85% HR) interspaced with 2.5 min of active or passive recovery. All exercise modalities increased oxygen uptake (V̇O2) (MD: ≥ 3.1 ml·kg−1·min−1, 95%CI: 1.5–4.7 ml·kg−1·min−1; P < 0.001), power output (MD: ≥ 26 W, 95%CI: 15–37 W; P < 0.001) and cycle duration (MD: ≥ 62 s, 95%CI: 36–88 s; P < 0.001) at 85% HRM. Significant pre-to-post differences were observed among all exercise groups for FMD (MD: ≥ 3.4%, 95%CI: 0.3–6.5%; P < 0.05), while MICT and P-HIT significantly increased the standard deviation of all NN intervals (SDNN) pre-to-post intervention (MD: ≥ 7 ms, 2–13 ms; P ≤ 0.05). Time-efficient HIT elicits significant improvements in cardiorespiratory fitness, FMD and autonomic modulation following a thrice weekly 12-week exercise intervention among sedentary middle-aged men. Active recovery between successive high-intensity intervals provided no additional benefit among this deconditioned cohort.

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.

Combined Effects Of Acute Aerobic Exercise Before And After Stretching On Brachial Artery Flow-mediated Dilation

PURPOSE: Decreased flow-mediated dilation (FMD) increases cardiovascular disease risks. Aerobic exercise or stretching generally increases brachial artery FMD, but resistance exercise does not. FMD responses would also alter by the order of exercise in combined exercise, and did not improve by resistance exercise after aerobic exercise. However, the combined effects of aerobic exercise and stretching order on FMD remain unclear. Thus, this study aimed to investigate the effect of aerobic exercise before and after stretching on FMD. METHODS:Fifteen healthy young males (21 &#177; 1 years) participated in three trials in random order on different days; 1) seated resting trial (REST); 2) aerobic exercise-stretching trial (AERO-ST); and 3) stretching-aerobic exercise trial (ST-AERO). A cycling ergometer exercise of 20 min at the intensity of 120 beats/min of heart rate levels was performed as an aerobic exercise, and four types of stretches of 20 min focusing on the lower limbs were performed. Before (Pre) and immediately (Post1) and 30 min (Post2) after trials, brachial artery FMD was measured by using ultrasound imaging system. RESULTS:No significant changes in all the parameters were observed in REST. In contrast, after AERO-ST and ST-AERO, FMD significantly increased at Post1 and Post2 compared to Pre, but the changes did not differ significantly between AERO-ST and ST-AERO (AERO-ST, Pre, 5.2 &#177; 0.2; Post1, 7.3 &#177; 0.6; Post2, 6.9 &#177; 0.5%, ST-AERO, Pre, 5.3 &#177; 0.3; Post1, 7.5 &#177; 0.5; Post2, 6.1 &#177; 0.5%, both P < 0.01). FMD in ST-AERO significantly differ between Post1 and Post2 (P < 0.01), and that at Post2 tended to return to Pre value. CONCLUSIONS:Therefore, these findings indicate that combined aerobic exercise and stretching would increase FMD, as an index of endothelial function, regardless of the aerobic exercise and stretching order. However, our results suggest that stretching after aerobic exercise may have prolonged effects on FMD improvement.

Exercise training and vascular function in postmenopausal individuals: a systematic review and meta-analysis.

Cardiovascular disease (CVD) is a leading cause of morbidity and mortality for menopausal individuals. Flow-mediated dilation (FMD), a surrogate marker of CVD, improves with aerobic exercise training in healthy and nonhealthy cohorts. However, systematic evaluation and precise estimate of this effect for menopausal individuals are unknown. We conducted a systematic review with meta-analysis to evaluate the influence of exercise training on FMD in postmenopausal individuals. Studies were identified from systematic search of major electronic databases (PubMed, ScienceDirect, and Cochrane Library) from inception to February 2021. Healthy, postmenopausal individuals were included, following an aerobic exercise intervention assessing FMD. A random-effects meta-analysis was used to calculate a pooled effect size (mean difference [MD]) with 95% confidence interval. Heterogeneity was assessed using I2 statistics. Metaregression was used to assess the association between changes in FMD and physical characteristics (eg, blood pressure, age, baseline FMD) and intervention details (metabolic equivalents and change in maximal oxygen uptake [∆V˙ o2max ]). For variables that significantly correlated, a multiple metaregression model was used to assess the accounted variance in between-study ∆FMD%. Study quality was assessed using the National Heart, Lung, and Blood Institute assessment tool. Nine studies, including 11 interventions (6 controlled interventions and 5 pre-post interventions; N = 182), with age range of 52 ± 4 to 64 ± 7 years underwent quantitative pooling of data. Exercise training significantly improved ∆FMD% (MD, 0.99; 95% confidence interval, 0.46-1.52; P < 0.001). Between-study heterogeneity was large and statistically significant ( I2 = 93.8%, P < 0.001). Post hoc analysis based on study design identified significant heterogeneity in the MD in ∆FMD% between controlled and pre-post study interventions ( P < 0.05). According to multiple metaregression, diastolic and systolic blood pressure and ∆V˙ o2max significantly predicted ∆FMD% ( Q = 15.74, df = 3, P < 0.01, R2 = 0.72). Aerobic exercise training improves FMD for postmenopausal individuals, and this observation was greater among controlled versus pre-post interventions. A higher resting blood pressure and the greatest ∆V˙ o2max yielded the largest improvements in FMD.

Blueberries Improve Endothelial Function in Postmenopausal Women With Above-Normal Blood Pressure via Reductions in Oxidative Stress

ObjectivesResearch suggests blueberries and their (poly)phenols may improve endothelial dysfunction, a major risk factor for cardiovascular disease (CVD). The objective of this study was to investigate the impact of consuming 22 g/day for 12 weeks of freeze-dried highbush blueberry powder on endothelial function and other measures of cardiovascular health, oxidative stress, and circulating (poly)phenol metabolites in postmenopausal women with above-normal blood pressure.MethodsWe performed a randomized, double-blind, placebo-controlled, parallel-arm trial in estrogen-deficient postmenopausal women aged 45–65 years with elevated blood pressure or stage 1-HTN. Endothelial function was assessed as brachial artery flow-mediated dilation (FMD) and normalized to individual shear rate area under the curve (FMD/SRAUC) to control for inter-individual variability in reactive hyperemia-induced shear stress. To assess whether improvements in FMD were mediated by reduced oxidative stress, FMD was assessed before and after intravenous infusion of a supra-physiologic dose of ascorbic acid. Blood pressure, arterial stiffness, and plasma (poly)phenol metabolites were also assessed.ResultsA total of 43 women completed the trial (n = 32 for endothelial function). Compliance in the Blueberry and Placebo groups were 93% and 91%, respectively. Mean total plasma (poly)phenol metabolite concentrations were increased at 4 (250,053 nmol/L, P < 0.05) and 8 (303,053 nmol/L, P < 0.05) weeks in the Blueberry group compared to baseline (125,798 nmol/L) with a strong trend at 12 weeks (227,971 nmol/L, P < 0.05), and no changes in Placebo. Blood pressure and arterial stiffness were unchanged with both treatments. At 12 weeks, FMD/SRAUC was increased by 96% from baseline (P < 0.05) in the Blueberry group but unchanged in Placebo, and changes in FMD/SRAUC from baseline to 12 weeks were higher (P < 0.05) than Placebo. The response in FMD/SRAUC to ascorbic acid infusion was lower (P < 0.05) at 12 weeks compared to baseline in the Blueberry group but not Placebo.ConclusionsThese findings suggest blueberries improve endothelial function, and is mediated, in part, by reduced oxidative stress in postmenopausal women with above-normal blood pressure, a high-risk population for developing CVD.Funding SourcesUS Highbush Blueberry Council and USDA National Institute of Food and Agriculture.

THE EFFECT OF RENAL DENERVATION ON PERIPHERAL AND CEREBRAL VASOREACTIVITY IN PATIENTS WITH RESISTANT HYPERTENSION AND TYPE 2 DIABETES MELLITUS

Objective: Vasoreactivity is fundamental mechanisms of the control of tissue perfusion, that distributes supply of blood flow according to metabolic needs and protecting the organs from changes in systemic blood pressure (BP). The presence of vascular risk factors such as hypertension (HTN) and diabetes mellitus (DM) impairs vasoreactivity, leading to an increased risk of stroke and myocardial infarction. The aim of this study was to evaluate the effect of renal denervation (RDN) on peripheral and cerebral vasoreactivity in patients with resistant HTN (RHTN) and type 2 DM at 6 month after procedure. Design and method: The assessment of the effect of RDN on peripheral vasoreactivity was performed in 31 patients with RHTN and type 2 DM, participants in single-arm prospective interventional studies (protocol numbers NCT02667912 and NCT01499810 at ClinicalTrials.gov) (mean age 59.1 ± 8.6 years, mean office (systolic/diastolic) BP (SBP/DBP) 167.7 ± 18.5/86.7 ± 16.6 mmHg, HbA1c 7.8 ± 1.8%, 22 (68%) men), of which cerebral vasoreactivity was evaluated in 21 patients with good visualization. All patients underwent ambulatory 24-hour BP. Flow-mediated dilation (FMD) of brachial artery and vasoreactivity of middle cerebral artery (MCA) during both breath-holding and hyperventilation testes were measured by high-resolution ultrasound at baseline and 6 month follow-up. Results: RDN led to a decrease in mean 24-hour BP (SBP/DBP) (from 157.5 ± 18.2/76.5 ± 9.7 to 147.8 ± 15.6/71 ± 12.8mmHg, p = 0.049/0.096) without significant changes in number of antihypertensive drugs (from 4.7 ± 0.9 to 4.5 ± 1.2, p = 0.52). There were increase in FMD (from 3.4 ± 5.5 to 7.7 ± 4.2%, p = 0.004), but vasoreactivity of MCA to hyperventilation and breath-holding test was not changed. The degree of improvement of FMD not correlated with the baseline BP and its change after RDN. Conclusions: According to our results, RDN in diabetic patients with RHTN improved peripheral vasoreactivity regardless of the degree of BP reduction, but did not significantly change cerebral vasoreactivity at 6 month follow up.

Consumption of a High‐fiber Diet Improves Systolic Blood Pressure and Vascular Endothelial Function and May Reduce Oxidative Stress in Middle‐aged to Older Adults

Aging is the primary risk factor for the development of cardiovascular diseases (CVD), largely due to increases in systolic blood pressure (SBP) and oxidative stress‐related impairments in vascular endothelial function. Higher intake of dietary fiber is associated with reduced CVD risk. In healthy late middle‐aged to older (MA/O) adults, limited evidence indicates high‐fiber diet interventions improve SBP, but whether a high‐fiber diet improves endothelial function with aging is unknown.PurposeWe tested the hypothesis that a high‐fiber diet would, in addition to reducing SBP, improve endothelial function and reduce oxidative stress in healthy MA/O adults.MethodsWe performed a controlled feeding study in which 14 MA/O adults (8F/6M; age: 69 ± 5 years) consumed an isocaloric high‐fiber diet (30‐35 g/day) for 7 days. Diets also contained 60% total carbohydrates, 15% protein, 25% fat, and 12‐15% sugar. Baseline (pre) measures were performed under habitual diet conditions (26 ± 6 g fiber/day). On days 0 (pre) and 7 (post) of the diet, endothelial cells were collected via venous endovascular biopsy, and endothelial function was assessed by brachial artery flow‐mediated dilation (FMD) following 20 minutes of intravenous infusion of saline (volume control) or the antioxidant ascorbic acid (0.06 g/kg fat‐free mass in 100 mL saline at 5 mL/min; N=12), to determine whether any improvements in endothelial functional following the high‐fiber diet were due to reduced oxidative stress.ResultsConsumption of a high‐fiber diet reduced SBP (pre vs. post: 120 ± 3 vs. 116 ± 3 mmHg, p&lt;0.01) and improved endothelial function by ~30% (pre vs. post: 4.1 ± 0.5 vs. 5.3 ± 0.7 %, p=0.03). Abundance of nitrotyrosine (NT), a marker of oxidative stress, in endothelial cells from a subset of subjects (N=6) was lower after the high‐fiber diet (pre vs. post: 0.43 ± 0.16 vs. 0.29 ± 0.12 A.U., p=0.08). At baseline, infusion of ascorbic acid increased FMD by 2.2 ± 0.7 %Δ units (p=0.01 vs. saline), indicating tonic suppression of endothelial function by oxidative stress under habitual diet conditions. Ascorbic acid still increased FMD post‐high‐fiber diet but to a lesser extent (+1.2 ± 0.6 %Δ units, p=0.06 vs. saline), and differences in FMD pre vs. post high‐fiber diet were abolished by ascorbic acid (6.3 ± 0.9 vs. 6.6 ± 0.9 %, p=0.68). These data suggest that the high‐fiber diet improved FMD in part by reducing oxidative stress.ConclusionsHigh‐fiber diet consumption improves SBP in healthy MA/O adults with normal baseline levels and induces clinically significant improvements in FMD possibly via reductions in vascular oxidative stress and tonic oxidative stress‐related suppression of endothelial function. These results suggest that a high‐fiber diet may reduce CVD risk, at least in part, by mitigating increases in SBP and oxidative stress‐related impairments in endothelial function with aging.

Endothelial dysfunction in acute and long standing COVID−19: A prospective cohort study

BackgroundCoronavirus disease-19 (COVID-19) is implicated by active endotheliitis, and cardiovascular morbidity. The long-COVID-19 syndrome implications in atherosclerosis have not been elucidated yet. We assessed the immediate, intermediate, and long-term effects of COVID-19 on endothelial function. MethodsIn this prospective cohort study, patients hospitalized for COVID-19 at the medical ward or Intensive Care Unit (ICU) were enrolled and followed up to 6 months post-hospital discharge. Medical history and laboratory examinations were performed while the endothelial function was assessed by brachial artery flow-mediated dilation (FMD). Comparison with propensity score-matched cohort (control group) was performed at the acute (upon hospital admission) and follow-up (1 and 6 months) stages. ResultsSeventy-three patients diagnosed with COVID-19 (37% admitted in ICU) were recruited. FMD was significantly (p < 0.001) impaired in the COVID-19 group (1.65 ± 2.31%) compared to the control (6.51 ± 2.91%). ICU-treated subjects presented significantly impaired (p = 0.001) FMD (0.48 ± 1.01%) compared to those treated in the medical ward (2.33 ± 2.57%). During hospitalization, FMD was inversely associated with Interleukin-6 and Troponin I (p < 0.05 for all). Although, a significant improvement in FMD was noted during the follow-up (acute: 1.75 ± 2.19% vs. 1 month: 4.23 ± 2.02%, vs. 6 months: 5.24 ± 1.62%; p = 0.001), FMD remained impaired compared to control (6.48 ± 3.08%) at 1 month (p < 0.001) and 6 months (p = 0.01) post-hospital discharge. ConclusionCOVID-19 patients develop a notable endothelial dysfunction, which is progressively improved over a 6-month follow-up but remains impaired compared to healthy controls subjects. Whether chronic dysregulation of endothelial function following COVID-19 could be accompanied by a residual risk for cardiovascular and thrombotic events merits further research.

Impact of ALLopurInol on ENdothelial funCtion in diabEtic patients affected with coronary artery disease: ALLIENCE trial

Allopurinol, a xanthine oxidase inhibitor, was shown to be useful in improving endothelial dysfunction in diabetic patients independently from their coronary status. We sought to assess the impact of allopurinol on endothelial function in diabetic patients with coronary artery disease (CAD) reputed to have severe endothelial dysfunction. We performed a simple-blind randomized trial enrolling patients with type 2 diabetes and CAD who underwent percutaneous coronary intervention. Patients were randomly assigned to either conventional optimal medical therapy alone (control group) or optimal medical therapy associated with high dose of allopurinol: 300 mg daily the first month then 600 mg daily the second month (allopurinol group). Endothelial function was assessed by flow-mediated dilation (FMD). The primary endpoint was the changes in FMD (Δ FMD) at 2 months. The secondary endpoints were the changes in endothelium-independent brachial dilation, and quality of life (QoL) as assessed by the Seattle Angina Questionnaire. A total of 64 patients (mean age 58.5 ± 8.3 years, 84.1% males) were randomly assigned to either allopurinol group ( n = 32) and control group ( n = 32). At baseline, FMD was comparable between the two groups ( P = 0.961). At 2 months, no significant change was observed in FMD between allopurinol group and control group ( P = 0.709). Regarding QoL, patients in allopurinol group showed better improvement in angina frequency ( P = 0.020) and disease perception ( P < 0.001) than controls. Subgroups analysis revealed that allopurinol was associated with significant improvement in FMD only in patients with poorly controlled diabetes (HBA1c > 8%) ( P = 0.010) and those with acid uric serum level ≤ 287 μmol/L ( P = 0.010) ( Fig. 1 ). Although allopurinol improved QoL (particularly angina frequency) in CAD diabetic patients, it did not improve the endothelial function except in those with poorly controlled diabetes and low acid uric serum level.