Significant Increase In Flow-mediated Dilation Research Articles

Effect of Low Protein Diet Supplemented with Ketoanalogs on Endothelial Function and Protein-Bound Uremic Toxins in Patients with Chronic Kidney Disease.

Studies have demonstrated that a low-protein diet supplemented with ketoanalogs (KAs) could significantly retard progression of renal function in patients with chronic kidney disease (CKD) stages 3-5. However, its effects on endothelial function and serum levels of protein-bound uremic toxins remain elusive. Therefore, this study explored whether a low-protein diet (LPD) supplemented with KAs affects kidney function, endothelial function, and serum uremic toxin levels in a CKD-based cohort. In this retrospective cohort, we enrolled 22 stable CKD stage 3b-4 patients on LPD (0.6-0.8 g/day). Patients were categorized into control (LPD only) and study groups (LPD + KAs 6 tab/day). Serum biochemistry, total/free indoxyl sulfate (TIS/FIS), total/free p-cresyl sulfate (TPCS/FPCS), and flow-mediated dilation (FMD) were measured before and after 6 months of KA supplementation. Before the trial, there were no significant differences in kidney function, FMD, or uremic toxin levels between the control and study groups. When compared with the control group, the paired t-test showed a significant decrease in TIS and FIS (all p < 0.05) and a significant increase in FMD, eGFR, and bicarbonate (all p < 0.05). In multivariate regression analysis, an increase in FMD (p < 0.001) and a decrease in FPCS (p = 0.012) and TIS (p < 0.001) remained persistent findings when adjusted for age, systolic blood pressure (SBP), sodium, albumin, and diastolic blood pressure (DBP). LPD supplemented with KAs significantly preserves kidney function and provides additional benefits on endothelial function and protein-bound uremic toxins in patients with CKD.

Wild blueberry (poly)phenols can improve vascular function and cognitive performance in healthy older individuals: a double-blind randomized controlled trial

BackgroundEvidence suggests that the intake of blueberry (poly)phenols is associated with improvements in vascular function and cognitive performance. Whether these cognitive effects are linked to increases in cerebral and vascular blood flow or changes in the gut microbiota is currently unknown. MethodsA double-blind, parallel randomized controlled trial was conducted in 61 healthy older individuals aged 65–80 y. Participants received either 26 g of freeze-dried wild blueberry (WBB) powder (302 mg anthocyanins) or a matched placebo (0 mg anthocyanins). Endothelial function measured by flow-mediated dilation (FMD), cognitive function, arterial stiffness, blood pressure (BP), cerebral blood flow (CBF), gut microbiome, and blood parameters were measured at baseline and 12 wk following daily consumption. Plasma and urinary (poly)phenol metabolites were analyzed using microelution solid-phase extraction coupled with liquid chromatography–mass spectrometry. ResultsA significant increase in FMD and reduction in 24 h ambulatory systolic BP were found in the WBB group compared with the placebo group (0.86%; 95% CI: 0.56, 1.17, P < 0.001; −3.59 mmHg; 95% CI: −6.95, −0.23, P = 0.037; respectively). Enhanced immediate recall on the auditory verbal learning task, alongside better accuracy on a task-switch task was also found following WBB treatment compared with placebo (P < 0.05). Total 24 h urinary (poly)phenol excretion increased significantly in the WBB group compared with placebo. No changes in the CBF or gut microbiota composition were found. ConclusionsDaily intake of WBB powder, equivalent to 178 g fresh weight, improves vascular and cognitive function and decreases 24 h ambulatory systolic BP in healthy older individuals. This suggests that WBB (poly)phenols may reduce future CVD risk in an older population and may improve episodic memory processes and executive functioning in older adults at risk for cognitive decline.Clinical Trial Registration number in clinicaltrials.gov: NCT04084457.

Effect of Potassium Supplementation on Endothelial Function: A Systematic Review and Meta-Analysis of Intervention Studies.

(1) Background: Endothelial dysfunction is an early predictor of cardiovascular diseases. Although a large body of evidence shows an inverse association between potassium intake and cardiovascular risk, the studies on endothelial function provided contrasting results. Thus, we carried out a systematic review and a meta-analysis of the available intervention studies of the potassium supplementation on endothelial function. (2) Methods: A systematic search of the online databases available (up to December 2022) was conducted including the intervention trials that reported flow-mediated dilation (FMD) changes-a non-invasive method of assessing endothelial function-after two different potassium intake regimens. For each study, the mean difference (MD) and 95% confidence intervals were pooled using a random effect model. (3) Results: Five studies met the pre-defined inclusion criteria and provided eight cohorts with 332 participants. In the pooled analysis, potassium supplementation was associated with a significant increase in FMD (MD: 0.74%), with a higher effect for a urinary potassium excretion higher than 90 mmol/day. There was a moderate heterogeneity among studies (I2 = 59%), explained by the different amount of potassium supplementation. (4) Conclusions: The results of our meta-analysis indicate that dietary potassium supplement improves endothelial function. This effect is directly associated with the amount of potassium supplement. The findings support the campaigns in favour of an increase in dietary potassium intake to reduce cardiovascular risk.

Effect of heat-moisture treated brown rice crackers on postprandial flow-mediated dilation in adults with mild endothelial dysfunction

BackgroundEndothelial dysfunction is an early pathophysiological feature and independent predictor of a poor prognosis in most forms of cardiovascular disease. We evaluated the effect of brown rice crackers (BR-C) on endothelial function. MethodsEffect of heat-moisture treated (HMT) -BR-C on postprandial flow-mediated dilation (FMD) in adults with mild endothelial dysfunction was compared with that of BR-C and white rice crackers (WR-C) in 12 adults with mild endothelial dysfunction (less than 7.0% of FMD) by a randomized, single-blind, three-treatment three-period crossover trial (UMIN 000034898). Since we considered that the FMD increase was associated with the treatment of HMT-BR-C, we examined the effect of three possible factors: postprandial glucose levels, polyphenol content, and polyphenol release from the food matrix. ResultsMean pre-intake baseline FMD values of HMT-BR-C, BR-C, and WR-C were 4.9%, 5.1%, and 4.9%, respectively, and those values 1 h post-intake were 6.3%, 5.1%, and 4.8%, respectively. There was no difference in intergroup comparisons of FMD using Dunnett's multiple comparison test. There was a significant increase in FMD only in HMT-BR-C in intragroup comparisons (P = 0.042 by paired-t test). In comparison with BR-C, no significant difference was noted in the postprandial glucose level nor in the content of total polyphenols and ferulic acid derivatives in HMT-BR-C. However, the 70% ethanol extracted from HMT-BR-C contained a significantly larger amount of free and bound ferulic acids than from BR-C. ConclusionHMT-BR-C intake increased the postprandial FMD response.

META-ANALYSIS ADDRESSING THE EFFECT OF SODIUM-GLUCOSE CO-TRANSPORTER-2 INHIBITORS ON FLOW-MEDIATED DILATION IN PATIENTS WITH TYPE 2 DIABETES MELLITUS

Objective: Endothelial dysfunction seems to play a pivotal role in the pathogenesis of cardiovascular disease and related complications among high-risk patients, such as those suffering from type 2 diabetes mellitus (T2DM). Non-invasive peripheral endothelial function assessment with measurement of brachial artery flow-mediated dilation (FMD) has been demonstrated to predict adverse cardiovascular events. Herein, we sought to determine whether SGLT-2 inhibitors provide a significant effect on endothelial function, as assessed through FMD. Design and method: We searched PubMed, Cochrane Library and grey literature from inception to 10th October 2021 for parallel group randomized controlled trials (RCTs) enrolling adult subjects with T2DM, assigned to a SGLT-2 inhibitor versus placebo or active comparator and addressing their effect on FMD. We set as primary efficacy outcome the change in FMD with SGLT-2 inhibitor versus control. Results: We pooled data from 4 trials in a total of 270 subjects with T2DM. We demonstrated that treatment with SGLT-2 inhibitor versus placebo or active comparator produced a significant increase in FMD by 1.66% (95% CI; 0.56 – 2.76, I2 = 28%, p = 0.003). Notably, all eligible RCTs utilized dapagliflozin. Overall risk of bias was evaluated as low across the selected studies. Conclusions: The present meta-analysis demonstrated a clear benefit on endothelial function with SGLT-2 inhibitors compared to placebo or active comparator. Although the sample size is small, it seems that amelioration of endothelial dysfunction with SGLT-2 inhibitors constitutes another significant mechanism that confers to cardio-protection with this drug class. Larger RCTs will shed further light on this important pathophysiologic link.

The effect of walnut consumption on cardiometabolic profiles of individuals with abnormal glucose homoeostasis: a systematic review and meta-analysis of clinical trials.

Findings on the effect of walnut consumption on cardiometabolic profiles in individuals with abnormal glucose homoeostasis are conflicting. We summarised earlier data in this regard. A systematic literature search of relevant reports published in Medline/PubMed, ISI web of Science, EMBASE, SCOPUS and Google Scholar up to October 2020 was conducted. Randomised trials that enrolled individuals with abnormal glucose homoeostasis in which the main intervention was walnut consumption were included. Abnormal glucose homoeostasis was defined as a spectrum of impaired glucose tolerance or pre-diabetic status that is associated with insulin resistance. Twelve studies were included in systematic review and eight in meta-analysis. No significant effect of walnut consumption on anthropometric measures, including weighted mean difference (WMD: -0·13; 95 % CI -0·64, 0·39 kg), BMI (-0·08; 95 % CI -0·47, 0·32 kg/m2) and waist circumference (0·01; 95 % CI -0·50, 0·52 cm) was observed. Although walnut intake did not influence on lipid profiles (including TAG, total- and HDL-cholesterol levels), individuals in the intervention group tended to have lower levels of LDL-cholesterol than those in the control group (-0·10; 95 % CI -0·20, 0·01 mmol/l; P = 0·06). Other cardiometabolic factors including markers of glycaemic control (fasting blood glucose and HbA1C levels), blood pressure and stimulus-adjusted response measure (a parameter of endothelial function) were not significantly affected. However, walnut consumption resulted in a significant increase in flow-mediated dilation (FMD) (0·93 %; 95 % CI 0·16, 1·71 %). Summarising earlier evidence, we found that walnut consumption might influence FMD and LDL-cholesterol levels in individuals with abnormal glucose homoeostasis. It did not affect other cardiometabolic profiles in these individuals.

Role of whey protein in vascular function: a systematic review and meta-analysis of human intervention studies.

Whey protein (WP) has been heavily appreciated as a rich source of bioactive peptides, with potential benefits for cardiovascular health. This study constitutes a systematic review and meta-analysis summarising the effects of WP consumption on vascular reactivity, arterial stiffness and circulatory biomarkers of vascular function. We searched electronic databases, including PubMed, SCOPUS and Web of science for relevant articles from inception to July 2020. Original clinical trials published in English-language journals that investigated the effects of WP on vascular function were eligible. A total of 720 records were identified in the initial search; from these, sixteen were included in our systematic review and thirteen in meta-analysis. The pooled analysis of six studies showed a significant increase in flow-mediated dilation (FMD) after WP consumption (weighted mean differences (WMD): 1·09 %, 95 % CI: 0·17, 2·01, P= 0·01). Meta-analysis of available data did not show any significant reduction in arterial stiffness measures including augmentation index (effect sizes: 7, WMD: -0·29 %, 95 % CI: -1·58, 0·98, P= 0·64) and pulse wave velocity (effect sizes: 4, WMD: -0·72 m/s, 95 % CI: -1·47, 0·03, P= 0·06). Moreover, the pooled analysis of six effect sizes showed no significant effects on plasma levels of nitric oxide following WP supplementation (WMD: 0·42 μmol/l, 95 % CI: -0·52, 1·36, P= 0·38). The overall results provided evidence supporting a protective effect of WP on endothelial function measured by FMD, but not for arterial stiffness measures and circulatory biomarker of vascular function. Further research is required to substantiate the benefits of WP on vascular function.

A Pilot Study of the Safety and Efficacy of Alkali Therapy on Vascular Function in Kidney Transplant Recipients

IntroductionMetabolic acidosis is associated with cardiovascular events, graft function, and mortality in kidney transplant recipients (KTRs). We examined the effect of alkali therapy on vascular endothelial function in KTRs.MethodsWe performed an 18-week, randomized, double-blind, placebo-controlled crossover pilot study examining the effect of sodium bicarbonate therapy versus placebo on vascular function in 20 adult KTRs at least 1 year from transplant with an estimated glomerular filtration rate (eGFR) ≥45 ml/min per 1.73 m2 and a serum bicarbonate level of 20 to 26 mEq/L. Each treatment period was 8 weeks in duration with a 2-week washout period between treatments. The primary outcome was change in brachial artery flow-mediated dilation (FMD) between sodium bicarbonate treatment and placebo.ResultsTwenty patients completed the study and were included in the primary analysis. The mean (SD) baseline eGFR of participants was 75 (22) ml/min per 1.73 m2, respectively. Serum bicarbonate levels did not increase significantly with treatment (0.3 [1.5] mEq/L, P = 0.37). Sodium bicarbonate therapy was not associated with worsening blood pressure, weight gain, or hypokalemia. There was no significant increase in FMD after 8 weeks of sodium bicarbonate therapy compared to placebo (mean change in FMD 2.2%, 95% CI –0.1 to 4.6, P = 0.06). There were no significant changes in high-sensitivity C-reactive protein, interleukin-6, eGFR, or urinary albumin-to-creatinine ratio during treatment. Urinary ammonium excretion decreased by 9 mmol/d (P=0.003), with sodium bicarbonate.ConclusionsSodium bicarbonate therapy is safe and feasible in KTRs, and our results strengthen the need for a larger randomized controlled trial.

Blood Orange Juice Consumption Increases Flow-Mediated Dilation in Adults with Overweight and Obesity: A Randomized Controlled Trial

Epidemiological studies have indicated an inverse association between citrus fruit consumption and cardiovascular disease (CVD) risk. There is, however, a paucity of data concerning effects of blood orange juice (BOJ) intake on endothelial function and cardiovascular risk biomarkers. We examined short-term effects of BOJ on endothelial function, blood pressure, lipid profile, and inflammatory markers in healthy participants of European origin who were overweight or obese. In a randomized, controlled, single-blind, crossover trial, 15 men and women (age: 28.7±6.5 y; BMI: 28.3±3.1 kg/m2) consumed BOJ or a sugar-matched control drink (CD) (200 mL twice daily) for 2 wk with a washout period of 1 wk. Endothelial function, measured as flow-mediated dilation (FMD) (primary outcome), and the secondary outcomes blood pressure, anthropometric measures, lipid profile, inflammatory markers, markers of vasodilation and vasoconstriction, and urinary flavanone metabolites were evaluated prior to and at the end of each treatment period following an overnight fast. Changes between treatments over time were assessed using repeated-measures ANOVA. The results demonstrate a significant increase in FMD following BOJ consumption (pre: 8.15%±2.92%; post: 10.2%±3.31%; P=0.002) compared with CD (pre: 8.11%±2.52%; post: 7.77%±2.43%; time × treatment interaction: P=0.001). Concurrent significant increases in urinary hesperetin-3'-glucuronide and hesperetin-7-glucuronide were observed following BOJ supplementation only (time × treatment interaction: P≤0.01). Baseline blood pressure, lipid profile, high-sensitivity C-reactive protein, and endothelin-1 were generally within healthy ranges and unaffected by the intervention. A 2-wk consumption of BOJ exerted favorable effects on endothelial function in healthy women and men who were overweight or obese, which is likely mediated by the combined actions of anthocyanin and flavanone metabolites on mechanisms that contribute to enhancing NO bioavailability. This trial was registered at clinicaltrials.gov as NCT03611114.

Allisartan Isoproxil Improves Endothelial Function and Vascular Damage in Patients with Essential Hypertension: A Single-Center, Open-Label, Randomized Controlled Trial.

Allisartan isoproxil is a novel angiotensin II type 1 receptor antagonist that has been confirmed to lower blood pressure and protect target organs effectively. However, its role in improving endothelial function and vascular damage has not been investigated yet. Patients with initially diagnosed mild essential hypertension (BP ranging from 140/90 to 159/99mmHg) with age from 25-75years were randomly assigned 1:1 to either the allisartan group (allisartan 240mg/day and lifestyle modification) or the lifestyle modification group and were followed up for 30days. Flow-mediated dilation (FMD), brachial-ankle pulse wave velocity (baPWV) and endothelialmicroparticles (EMPs) were measured for evaluation of endothelial function and vascular damage. In addition, we enrolled 36 normotensive individuals as healthy control. Seventy-two mildly hypertensive patients were enrolled in this study. After 30days of treatment, a significant increase in FMD was observed in the allisartan group (0.9 ± 0.7%, p < 0.001) and remained unchanged in the lifestyle modification group, but the difference between the two groups did not reach statistical significance (p = ns). EMPs, baPWV, SBP and DBP decreased by 251.0 ± 255.9 counts/μl (p < 0.001), 102.8 ± 84.2cm/s (p < 0.001), 13.20 ± 3.9mmHg (p < 0.001) and 9.35 ± 2.5mmHg (p < 0.001), respectively, in the allisartan group, while by 21.3 ± 84.3 counts/μl (p = ns), 0.4 ± 22.0cm/s (p = ns), 3.2 ± 6.0mmHg (p < 0.01) and 1.0 ± 2.5mmHg (p = ns), respectively, in the lifestyle modification group. All of the indexes above achieved statistical significance between the allisartan and lifestyle modification groups (p < 0.05). Besides, after 30days of allisartan administration baPWV and EMPs were comparable to those measured in the healthy control group, while the difference in SBP, DBP and FMD remained significant between the allisartan and healthy control groups (p < 0.05). The present study demonstrates for the first time that allisartan isoproxil exerts a favorable effect on improving endothelial function and vascular damage in patients with mild EH, making it a promising drug for management of EH. ChiCTR2000032332.

Effects of an Acute Pilates Program under Hypoxic Conditions on Vascular Endothelial Function in Pilates Participants: A Randomized Crossover Trial.

This study aimed to compare the effects of an acute Pilates program under hypoxic vs. normoxic conditions on the metabolic, cardiac, and vascular functions of the participants. Ten healthy female Pilates experts completed a 50-min tubing Pilates program under normoxic conditions (N trial) and under 3000 m (inspired oxygen fraction = 14.5%) hypobaric hypoxia conditions (H trial) after a 30-min exposure in the respective environments on different days. Blood pressure, branchial ankle pulse wave velocity, and flow-mediated dilation (FMD) in the branchial artery were measured before and after the exercise. Metabolic parameters and cardiac function were assessed every minute during the exercise. Both trials showed a significant increase in FMD; however, the increase in FMD was significantly higher after the H trial than that after the N trial. Furthermore, FMD before exercise was significantly higher in the H trial than in the N trial. In terms of metabolic parameters, minute ventilation, carbon dioxide excretion, respiratory exchange ratio, and carbohydrate oxidation were significantly higher but fat oxidation was lower during the H trial than during the N trial. In terms of cardiac function, heart rate was significantly increased during the H trial than during the N trial. Our results suggested that, compared to that under normoxic conditions, Pilates exercise under hypoxic conditions led to greater metabolic and cardiac responses and also elicited an additive effect on vascular endothelial function.

Pilates Exercise in Hypoxia Increases Vascular Endothelial Function in Professional Pilates Players

PurposeThe purpose of this study was to investigate the pilates exercise in hypoxia increases vascular endothelial function in professional Pilates players.MethodsTen healthy Pilates expert female (age: 26.9 ± 2.7, weight: 50.8 ± 5.2, BMI: 19.3 ± 1.4) completed two different trials on different days, consisting of exercise in normoxia (N trial) and exercise in 3,000 m simulated altitude (526 mmHg) hypobaric hypoxia (H trial). After 30 minutes of exposure in each environment, they performed tubing Pilates exercise for 50 minutes under normoxia and hypoxia. Pilates exercise using tubing were composed of 25 types, each performed for 2 minutes. Pilates motion is configured as follows : roll up &amp; down, biceps, arm circles, teaser, rolling, spine twist, mermaid, cobra, swimming, double kicks, swan, cat, thigh stretching, hug a tree, squat, row, saw, hip pull, hundred, lats pull, leg arc, scissor, helicopter, right side leg pull, left side leg pull. Metabolic parameters (minute ventilation; VE, oxygen uptake; VO2, carbon dioxide excretion; VCO2, respiratory exchange ratio; RER, carbohydrate oxidation; CO, fatty acid oxidation; FAO, energy expenditure; EE) and cardiac function (heart rate; HR, stroke volume; SV, cardiac output; CO, end‐diastolic volume; EDV, end‐systolic volume; ESV, ejection fraction; EF) were measured every minutes during Pilates exercise. The sum of the values measured for 50 minutes was used as the result (exceptionally, RER uses average values). Blood pressure (BP), branchial ankle pulse wave velocity (baPWV) and flow mediated dilation (FMD) in branchial artery were measured as vascular function before and after exercise.ResultsIn metabolic parameters, H trial showed significantly higher VE, VCO2, RER and CO than N trial. However, FAO was lower in H trial than in N trial. VO2 and EE. VO2 and EE presented no significant difference between the two trials. In cardiac function, HR showed a significant increase in H trial compared with N trial, however, the remaining cardiac function parameters did not show significant difference. In vascular function, BP (systolic blood pressure, diastolic blood pressure, pulse pressure and mean arterial pressure) and baPWV did not show significant interaction effects between exercise and environment. However, FMD presented a significant interaction effects between exercise and environment. As a result of the post‐hoc, both trial showed a significant increase in FMD via exercise and the increase rate in FMD was significantly higher in H trial (48.5 ± 22.9) than in N trial (34.9 ± 18.3). Also, H trial showed a significantly higher FMD before exercise than N trial.ConclusionOur results suggest that Pilates exercise under moderate hypoxia shows greater metabolic and cardiac response by relatively higher exercise intensity, and it also elicit synergy effect on vascular endothelial function than under normoxia in professional Pilates players.

The effects of curcumin supplementation on endothelial function: A systematic review and meta-analysis of randomized controlled trials.

Impaired endothelial function is an important risk factor for cardiovascular disease (CVD). Curcumin supplementation might be an appropriate approach to decrease the complications of CVD. Randomized controlled trials assessing the effects of curcumin supplementation on endothelial function were included. Two independent authors systematically searched online database including EMBASE, Scopus, PubMed, Cochrane Library, and Web of Science with no time restriction. Cochrane Collaboration risk of bias tool was applied to assess the methodological quality of included trials. Between-study heterogeneities were estimated using the Cochran's Q test and I-square (I2 ) statistic. Data were pooled using a random-effects model, and weighted mean differences (WMDs) were considered as the overall effect sizes. Ten studies with 11 effect sizes were included. We found a significant increase in flow-mediated dilation (FMD) following curcumin supplementation (WMD: 1.49; 95% CI [0.16, 2.82]). There was no effect of curcumin supplement on pulse wave velocity (PWV; WMD: -41.59; 95% CI [-86.59, 3.42]), augmentation index (Aix; WMD: 0.71; 95% CI [-1.37, 2.79]), endothelin-1 (ET-1; WMD: -0.30; 95% CI [-0.96, 0.37]), and soluble intercellular adhesion molecule-1 (sICAM-1; WMD: -10.11; 95% CI [-33.67, 13.46]). This meta-analysis demonstrated the beneficial effects of curcumin supplementation on improving FMD, though it did not influence PWV, Aix, Et-1, and sICAM-1.

Effects of aronia berry (poly)phenols on vascular function and gut microbiota: a double-blind randomized controlled trial in adult men

Aronia melanocarpa is a rich source of (poly)phenols. Previous research has demonstrated that these berries may provide cardiovascular health benefits in high-risk populations. However, very few studies have investigated the effects of daily consumption of dietary achievable amounts of the berries in healthy subjects. The aim of this study was to investigate the effects of aronia berries on vascular function and gut microbiota composition in a healthy population. A double-blind, placebo-controlled, parallel designed study was conducted in 66 healthy men randomly allocated to consume a (poly)phenol-rich extract (116 mg, 75 g berries), a whole fruit powder (12 mg, 10 g berries), or placebo (maltodextrin) for 12 wk. Flow-mediated dilation (FMD), arterial stiffness, blood pressure, heart rate, and serum biochemistry were assessed. Plasma (poly)phenol metabolites were analyzed by LC-MS. Gut microbiota composition was determined via 16S rRNA sequencing in stool samples. Consumption of aronia whole fruit and extract powder for 12 wk led to a significant increase in FMD over control of 0.9%±0.4% (95% CI: 0.13%, 1.72%) and 1.2%±0.4% (95% CI: 0.36%, 1.97%), respectively. Acute improvements in FMD were also observed 2 h after consumption of aronia extract on day 1 (1.1%±0.3%, P=0.003) and 12 wk later (1.5%±0.4%, P=0.0001). Circulating plasma phenolic metabolites increased upon consumption of the aronia treatments. Although no changes were found in gut microbiota diversity, consumption of aronia extract increased the growth of Anaerostipes (+10.6%, P=0.01), whereas aronia whole fruit showed significant increases in Bacteroides (+193%, P=0.01). Correlation analysis identified significant associations between changes in FMD, aronia-derived phenolic metabolites, and specific gut microbial genera. In healthy men, consumption of aronia berry (poly)phenols improved endothelial function and modulated gut microbiota composition, indicating that regular aronia consumption has the potential to maintain cardiovascular health in individuals at low risk of cardiovascular disease. This trial was registered at CLINICALTRIALs.gov as NCT03041961.

Effect of Treatment of Metabolic Acidosis on Vascular Endothelial Function in Patients with CKD: A Pilot Randomized Cross-Over Study.

We examined the effect of alkali replacement for metabolic acidosis on vascular endothelial function in patients with CKD. We performed a pilot, prospective, open-label 14-week crossover study examining the effect of oral sodium bicarbonate treatment on vascular function in 20 patients with an eGFR of 15-44 ml/min per 1.73 m2 with low serum bicarbonate levels (16-21 mEq/L). Each period was 6 weeks in duration with a 2-week washout period in between. Patients were treated to goal serum bicarbonate of ≥23 mEq/L. The primary end point was change in brachial artery flow-mediated dilation (FMD) between treatment and control conditions. Secondary end points included changes in markers of inflammation, bone turnover, mineral metabolism, and calcification. Eighteen patients completed the study and were included in the primary efficacy analysis. The mean (SD) age and eGFR were 59 (12) years and 26 (8) ml/min per 1.73 m2, respectively. Serum bicarbonate increased significantly with sodium bicarbonate treatment (+2.7±2.9 mEq/L, P≤0.001), whereas there was no change in bicarbonate levels in the control group. FMD significantly improved after sodium bicarbonate therapy (mean±SD, FMD baseline: 4.1%±4.1%; 6 weeks: 5.2%±2.9%; P=0.04) There was no significant change in FMD in the control group (mean±SD, FMD baseline: 4.6%±3.1%; 6 weeks: 4.1%±3.4%; P=0.20). Compared with control, sodium bicarbonate treatment resulted in a significant increase in FMD (mean, 1.8%; 95% confidence interval, 0.3 to 3.3; P=0.02). There was no significant change in bone markers or serum calcification propensity with treatment. Serum phosphorus and intact fibroblast growth factor 23 increased significantly during treatment. Treatment of metabolic acidosis with sodium bicarbonate significantly improved vascular endothelial function in patients with stages 3b and 4 CKD.

Effects of continuous positive airway pressure on cardiovascular biomarkers in patients with obstructive sleep apnea: a meta-analysis of randomized controlled trials.

Obstructive sleep apnea (OSA) is associated with increased levels of systemic inflammatory markers, increased arterial stiffness, and endothelial dysfunction, which may lead to increased cardiovascular risk. We aimed to quantify the effects of continuous positive airway pressure (CPAP) on cardiovascular biomarkers and to establish predictors of response to CPAP. We searched PubMed and the Cochrane Library from inception to May 31, 2017. Randomized controlled trials (RCTs) assessing the efficacy of CPAP on high-sensitivity C-reactive protein (hs-CRP), interleukin 6 (IL-6), tumor necrosis factor- alpha (TNF-α), augmentation index (AIx), pulse wave velocity (PWV), and flow-mediated dilatation (FMD) in patients with OSA were selected by consensus. We included 15 RCTs comprising 1090 patients in the meta-analysis. The pooled standard mean difference (SMD) of effect of CPAP on hs-CRP was - 0.64 (95% confidence interval (CI) - 1.19 to - 0.09; P = 0.02). CPAP was associated with a reduction in AIx of 1.53% (95% CI, 0.80 to 2.26%; P < 0.001) and a significant increase in FMD of 3.96% (95% CI 1.34 to 6.59%; P = 0.003). Subgroup analyses found CPAP was likely to be more effective in improving FMD levels in severe OSA patients or patients with effective CPAP use ≥ 4h/night. Among patients with OSA, CPAP improves inflammatory marker hs-CRP, arterial stiffness marker AIx, and endothelial function marker FMD. These biomarkers may provide information related to response to treatment. Future studies will need to clarify the efficacy of these biomarkers in assessing cardiovascular risk reduction among OSA treated with CPAP.

Flavonoid-Rich Apple Improves Endothelial Function in Individuals at Risk for Cardiovascular Disease: A Randomized Controlled Clinical Trial.

The cardioprotective effects of apples are primarily attributed to flavonoids, found predominantly in the skin. This study aimed to determine if acute and/or chronic (4 weeks) ingestion of flavonoid-rich apples improves endothelial function, blood pressure (BP), and arterial stiffness in individuals at risk for cardiovascular diseases (CVD). In this randomized, controlled cross-over trial, acute and 4 week intake of apple with skin (high flavonoid apple, HFA) is compared to intake of apple flesh only (low flavonoid apple, LFA) in 30 participants. The primary outcome is endothelial function assessed using flow-mediated dilation (FMD) of the brachial artery, while main secondary outcomes are 24 h ambulatory BP and arterial stiffness. Other outcomes include fasting serum glucose and lipoprotein profile, plasma heme oxygenase-1 (Hmox-1), F2 -isoprostanes, flavonoid metabolites, and plasma and salivary nitrate (NO3- ) and nitrite (NO2- ) concentrations. Compared to LFA control, the HFA results in a significant increase in FMD acutely (0.8%, p<0.001) and after 4 weeks chronic intake (0.5%, p<0.001), and in plasma flavonoid metabolites (p<0.0001). Other outcomes are not altered significantly. A lower risk of CVD with higher apple consumption could be mediated by the beneficial effect of apple skin on endothelial function, both acutely and chronically.

Effects of Allopurinol on Endothelial Function: A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Trials.

Uric acid (UA), the final product of purine catabolism, may be associated with an increased risk of cardiovascular disease. The aim of this meta-analysis of randomized placebo-controlled trials was to evaluate whether lowering serum UA (SUA) levels with allopurinol is associated with improved flow-mediated dilation (FMD), a validated marker of early vascular damage. A literature search was carried out from inception until 20 June 2017. Meta-analysis was performed using an inverse variance-weighted, random-effects model with standardized mean difference (SMD) as the effect size estimate. Meta-analysis of data from the ten eligible randomized controlled trials (RCTs), with 670 subjects, suggested a significant increase in FMD following allopurinol treatment (weighted mean difference [WMD] 1.79%, 95% confidence interval [CI] 1.01-2.56, p<0.001; I 2: 86.77%). The effect size was robust and remained significant after omission of each single study. Subgroup analyses of RCTs based on the administered dose or duration of treatment did not reveal any significant impact of these variables on FMD change. Nor was a significant association found between allopurinol-induced changes in SUA levels and FMD (slope 0.46, p=0.253), whereas baseline FMD significantly influenced the degree of FMD improvement following allopurinol treatment (slope 0.52, p=0.022). Nitroglycerin-mediated dilation was not altered by allopurinol treatment (WMD 0.88%, 95% CI -1.15-2.91, p=0.395; I 2: 80.88%). This meta-analysis of available RCTs suggests a significant benefit from allopurinol intake in increasing FMD in humans, independent of its effect on SUA levels.

Effects of disturbed blood flow during exercise on endothelial function: a time course analysis.

This study aimed to examine the time course of endothelial function after a single handgrip exercise session combined with blood flow restriction in healthy young men. Nine participants (28±5.8 years) completed a single session of bilateral dynamic handgrip exercise (20 min with 60% of the maximum voluntary contraction). To induce blood flow restriction, a cuff was placed 2 cm below the antecubital fossa in the experimental arm. This cuff was inflated to 80 mmHg before initiation of exercise and maintained through the duration of the protocol. The experimental arm and control arm were randomly selected for all subjects. Brachial artery flow-mediated dilation (FMD) and blood flow velocity profiles were assessed using Doppler ultrasonography before initiation of the exercise, and at 15 and 60 min after its cessation. Blood flow velocity profiles were also assessed during exercise. There was a significant increase in FMD 15 min after exercise in the control arm compared with before exercise (64.09%±16.59%, P=0.001), but there was no change in the experimental arm (-12.48%±12.64%, P=0.252). FMD values at 15 min post-exercise were significantly higher for the control arm in comparison to the experimental arm (P=0.004). FMD returned to near baseline values at 60 min after exercise, with no significant difference between arms (P=0.424). A single handgrip exercise bout provoked an acute increase in FMD 15 min after exercise, returning to near baseline values at 60 min. This response was blunted by the addition of an inflated pneumatic cuff to the exercising arm.

Endothelial Function in Children With OSA and the Effects of Adenotonsillectomy

The association between childhood OSA and endothelial function as measured by flow-mediated dilation (FMD) and its response to OSA treatment are uncertain. The objective of this study was to compare FMD in children with OSA with nonsnoring control subjects and to examine its response to treatment. Index cases were children aged 6 to 18 years with habitual snoring and polysomnography (PSG)-confirmed OSA (obstructive apnea hypopnea index [OAHI] > 1 events/h). Each case was paired with an age-, sex-, and BMI-matched nonsnoring control subject recruited from our previous community growth survey. All subjects underwent FMD measurement in the morning after overnight PSG. Adenotonsillectomy (AT) was offered to subjects who satisfied predefined AT operation criteria. All cases underwent repeat PSG and FMD assessment 6 months later. A total of 63 case-control pairs were recruited. The OSA group had a significantly higher OAHI (median, 5.3 events/h [interquartile range (IQR), 2.6-11.7] vs 0.2 events/h [IQR, 0-0.5], P < .001) and lower FMD (mean ± SD, 7.9% ± 1.3% vs 8.3% ± 0.8%; P = .04) than the control group. Thirty-two case subjects underwent AT. A significant reduction in OAHI was documented in the AT group (-8.8 events/h [IQR, -13.7 to -4.7]; P < .001) accompanied by a significant increase in FMD (+0.6% [IQR, 0.4-1.4]; P < .001), which was not observed in subjects who did not undergo AT. Children with OSA had reduced FMD, which was reversible with treatment.