Improvement In Flow-mediated Dilation Research Articles

Abstract 11544: Rosuvastatin Dose-dependently Improves Flow-mediated Dilation, but Reduces Adiponectin Levels and Insulin Sensitivity in Hypercholesterolemic Patients

Background: Genetic analysis from patients participated in the randomized trials reported that the increased risk of type 2 diabetes noted with statins is at least partially explained by HMG-coenzyme A reductase inhibition. We investigated vascular and metabolic phenotypes of different dosages of rosuvastatin in hypercholesterolemic patients. Methods: This was a randomized, single-blind, placebo-controlled, parallel study. Age, sex, and body mass index were matched among groups. Forty-eight patients were given placebo, and 47, 48, and 47 patients given rosuvastatin 5,10, and 20 mg, respectively daily during a 2 month treatment period. Results: Placebo therapy did not significantly change insulin, adiponectin, glycated hemoglobin, and insulin sensitivity relative to baseline measurements. Rosuvastatin 5,10, and 20 mg dose-dependently and significantly improved flow-mediated dilation (34, 40, and 46%) after 2 months therapy when compared with baseline ( P <0.001 by paired t -test) or when compared with placebo ( P <0.001 by ANOVA). Rosuvastatin 5,10, and 20 mg dose-dependently and significantly increased insulin (median % changes; 16, 20, and 20%, respectively) and glycated hemoglobin levels (mean % changes; 2, 2, and 3%, respectively), and decreased adiponectin levels (mean % changes; 3, 9, and 14%, respectively) and insulin sensitivity (mean % changes; 2, 3, and 4%, respectively) after 2 months therapy when compared with either baseline (all P <0.05 by paired t -test). These effects with rosuvastatin 5,10, and 20 mg were significant when compared with placebo ( P =0.006 for insulin, P =0.012 for glycated hemoglobin, P =0.007 for adiponectin, and P =0.002 for insulin sensitivity by ANOVA). Conclusions: Despite beneficial reductions in LDL cholesterol and improvement of flow-mediated dilation, rosuvastatin treatment dose-dependently and significantly resulted in decreasing insulin sensitivity and increasing ambient glycemia by reducing adiponectin levels and increasing insulin levels in hypercholesterolemic patients.

Effect of potassium supplementation on vascular function: A meta-analysis of randomized controlled trials

BackgroundEffects of potassium supplementation on vascular function remain conflicting. This meta-analysis aimed to summarized current literature to fill the gaps in knowledge. MethodsA literature search was performed on PubMed database through April, 2016. The measurements of vascular function included pulse wave velocity (PWV), augmentation index (AI), pulse pressure (PP), flow mediated dilatation (FMD), glycerol trinitrate responses (GTN), and intercellular cell adhesion molecule-1 (ICAM-1). Data were pooled as standardized mean difference (SMD) with 95% confidence intervals. ResultsSeven randomized controlled trials examining 409 participants were included, with dosage of potassium ranging from 40 to 150mmol/day, and duration of intervention from 6days to 12months. Pooling results revealed a significant improvement in PP (SMD −0.280, 95% CI −0.493 to −0.067, p=0.010), but no improvement in PWV (SMD −0.342, 95% CI −1.123 to 0·440, p=0.391), AI (SMD −0.114, 95% CI −0.282 to 0.054, p=0.184), FMD (SMD 0·278, 95% CI −0.321 to 0.877, p=0.363), GTN (SMD −0.009, 95% CI −0.949 to 0.930, p=0.984), and ICAM-1 (SMD −0.238, 95% CI −0.720 to 0.244, p=0.333). ConclusionsPotassium supplementation was associated with significant improvement of PP, rather than other measurements of vascular function. However, the small number of researches and wide variation of evidences make it difficult to make a definitive conclusion.

Heart Rate reduction by IVabradine for improvement of ENDothELial function in patients with coronary artery disease: the RIVENDEL study.

Data from experimental studies suggest that the f current-inhibitor ivabradine may reduce oxidative stress and improve endothelial function. We aimed to evaluate the effect of ivabradine on endothelial function in patients with coronary artery disease (CAD) after complete revascularization with percutaneous coronary angioplasty (PCI). At least 30days after PCI, 70 patients were randomized (T0) to receive ivabradine 5mg twice daily (ivabradine group, n=36) or to continue with standard medical therapy (control group, n=34). After 4weeks (T1), ivabradine dose was adjusted up to 7.5mg twice daily in patients with heart rate (HR) at rest >60bpm, and thereafter continued for additional 4weeks (T2). At all timings, brachial artery reactivity was assessed by flow-mediated dilatation (FMD) and nitroglycerin-mediated dilatation (NMD). No significant differences were observed at T0 between ivabradine and control groups in terms of HR (68.0±6.4 vs. 67.6±6.4bpm; p=0.803), FMD (8.7±4.9 vs. 8.0±5.5%; p=0.577) and NMD (12.7±6.7 vs. 13.3±6.2%; p=0.715). Over the study period, a significant reduction of HR (65.2±5.9bpm at T1, 62.2±5.7bpm at T2; p<0.001), and improvement of FMD (12.2±6.2% at T1, 15.0±7.7% at T2; p<0.001) and NMD (16.6±10.4% at T1, 17.7±10.8 at T2; p<0.001) were observed in the ivabradine group, while no significant changes were observed in the control group. In the ivabradine group, a moderate negative correlation was observed between the HR variation and FMD variation from T1 to T3 (r=-0.448; p=0.006). In patients with CAD undergoing complete revascularization with PCI, addition of ivabradine to the standard medical therapy produces a significant improvement in endothelial function. This effect seems to be related to HR reduction. ClinicalTrials.gov number, NCT02681978.

Rosuvastatin dose-dependently improves flow-mediated dilation, but reduces adiponectin levels and insulin sensitivity in hypercholesterolemic patients

BackgroundGenetic analysis from patients participated in the randomized trials reported that the increased risk of type 2 diabetes noted with statins is at least partially explained by HMG-coenzyme A reductase inhibition. We investigated vascular and metabolic phenotypes of different dosages of rosuvastatin in hypercholesterolemic patients. MethodsA randomized, single-blind, placebo-controlled, parallel study was conducted in 48 patients on placebo, and in 47, 48, and 47 patients given daily rosuvastatin 5, 10, and 20mg, respectively during a 2month treatment period. ResultsRosuvastatin 5, 10, and 20mg improved flow-mediated dilation (34, 40, and 46%) after 2months therapy when compared with baseline (P<0.001 by paired t-test) and when compared with placebo (P<0.001 by ANOVA). Rosuvastatin 5,10, and 20mg dose-dependently and significantly increased insulin (mean % changes; 19, 29, and 31%, respectively) and glycated hemoglobin levels (mean % changes; 2, 2, and 3%, respectively), and decreased adiponectin levels (mean % changes; 3, 9, and 14%, respectively) and insulin sensitivity (mean % changes; 2, 3, and 4%, respectively) after 2months therapy when compared with baseline (all P<0.05 by paired t-test). These effects with rosuvastatin 5, 10, and 20mg were significant when compared with placebo (P=0.006 for insulin, P=0.012 for glycated hemoglobin, P=0.007 for adiponectin, and P=0.002 for insulin sensitivity by ANOVA). ConclusionsDespite beneficial reductions in LDL cholesterol and improvement of flow-mediated dilation, rosuvastatin dose-dependently and significantly resulted in decreasing insulin sensitivity and increasing ambient glycemia by reducing adiponectin levels and increasing insulin levels in hypercholesterolemic patients.

Does epicatechin contribute to the acute vascular function effects of dark chocolate? A randomized, crossover study.

Cocoa, rich in flavan-3-ols, improves vascular function, but the contribution of specific flavan-3-ols is unknown. We compared the effects of pure epicatechin, a major cocoa flavan-3-ol, and chocolate. In a randomized crossover study, twenty healthy men (40-80 years) were supplemented with: (1) 70g dark chocolate (150 mg epicatechin) with placebo capsules; (2) pure epicatechin capsules (2 × 50 mg epicatechin) with 75g white chocolate; and (3) placebo capsules with 75 g white chocolate (0 mg epicatechin). Vascular function (flow-mediated dilation (FMD) and augmentation index (AIx)) were measured before and 2 hours after interventions. Epicatechin metabolites time-profiles were measured in blood to calculate the bioavailability. Pure epicatechin did not significantly improve FMD (+0.75%; p = 0.10) or AIx (-2.2%; p = 0.23) compared to placebo. Dark chocolate significantly improved FMD (+0.96%; p = 0.04) and AIx (-4.6%; p = 0.02). Differences in improvements in FMD (+ 0.21%; p = 0.65) or Aix (-2.4%; p = 0.20) between pure epicatechin and dark chocolate were not significant. The bioavailability of epicatechin did not differ between pure epicatechin and dark chocolate (p = 0.14). Despite differences in epicatechin dose, improvements in vascular function after pure epicatechin and chocolate were similar and the bioavailability did not differ, suggesting a role for epicatechin.

Endothelial function following glucose ingestion in adults with prediabetes: Role of exercise intensity.

To determine whether high intensity exercise (HIE) would improve endothelial function more than an isocaloric bout of moderate intensity exercise (MIE) following glucose ingestion in adults with prediabetes. Twelve subjects with prediabetes completed all three conditions: time-course matched control and isocaloric exercise (∼200 kcal) at moderate (MIE; at lactate threshold) and high intensity (HIE; 75% of difference between lactate threshold and VO2 peak). Brachial artery flow-mediated dilation (FMD) was measured before exercise (baseline), within 30 min postexercise, and 1 and 2 hr following a 75 g oral glucose tolerance test (OGTT). Plasma F2-isoprostanes were also assessed during the protocol (i.e., baseline to 2 hr OGTT) as a biomarker of oxidative stress. MIE reduced postexercise F2-isoprostanesAUC compared with time-course matched control and HIE. Although exercise had no statistical effect on FMD postexercise or during the OGTT, elevations in FMDAUC after MIE and HIE were associated with reduced postexercise F2-isoprostanesAUC . Exercise at either intensity had no effect on FMD immediately postexercise following glucose administration. However, individuals with reduced oxidative stress responses to exercise had greater exercise-induced improvement in FMD. Further work is required to identify the mechanism by which exercise alters oxidative stress to enhance endothelial function.

Impact of Real-Time Continuous Glucose Monitoring Use on Glucose Variability and Endothelial Function in Adolescents with Type 1 Diabetes: New Technology--New Possibility to Decrease Cardiovascular Risk?

Children with type 1 diabetes (T1DM) are the high-risk group of accelerated atherosclerosis. Real-time continuous glucose monitoring (RT-CGM) provides possibilities for the detection of glycaemic variability, newly recognized cardiovascular risk factor. The aim of the study was to assess the usefulness of RT-CGM as an educational tool to find and reduce glycaemic variability in order to improve endothelial function in T1DM adolescents. Forty patients aged 14.6 years were recruited. The study was based on one-month CGM sensors use. Parameters of glycaemic variability were analyzed during first and last sensor use, together with brachial artery flow-mediated dilatation (FMD) to assess endothelial function. In the whole group, FMD improvement was found (10.9% to 16.6%, p < 0.005), together with decrease in all studied glycaemic variability parameters. In patients with HbA1c improvement compared to the group without HbA1c improvement, we found greater increase of FMD (12% to 19%, p < 0.005 versus 8.2% to 11.3%, p = 0.080) and greater improvement of glucose variability. RT-CGM can be considered as an additional tool that offers T1DM adolescents the quick reaction to decrease glycaemic variability in short time observation. Whether such approach might influence improvement in endothelial function and reduction of the risk of future cardiovascular disease remains to be elucidated.

Abstract 14275: The Impact of Continuous and Interval Aerobic Exercise on Endothelium, Arterial Wall Properties and Inflammatory Status

Introduction: Chronic aerobic exercise training is associated with favorable long term cardiovascular effects. Hypothesis: We investigated the acute effects of continuous moderate-intensity aerobic exercise (CAE) and high intensity interval aerobic exercise (hIAE) on endothelial function, arterial stiffness and inflammatory status in healthy subjects. Methods: Twenty healthy men (mean aged 22.6±3.3yr) were recruited in this cross-over study. They participated in two exercise sessions: a) CAE: volume at 50% of maximum aerobic work on a cycle ergometer for 30 min and b) hIAE: interval maximum aerobic work on a cycle ergometer for 30 min. Endothelial function was evaluated by flow-mediated dilation (FMD) in the brachial artery. Carotid-femoral pulse wave velocity (cfPWV) and femoral-dorsalis pedis PWV (fdPWV) were measured as indices of central aortic and peripheral arterial stiffness. Intereleukin (IL)-17 levels were measured with ELISA. Measurements were carried out before and immediately after each exercise session. Results: There was no significant differences in baseline measurements before CAE and hIAE, regarding FMD, cfPWV and fdPWV and IL-17 levels (p=NS for all). Both CAE (8.57±2.55% vs. 6.37±1.48% p&lt;0.001) and hIAE (8.48±2.60% vs. 5.95±1.78% p&lt;0.001) significantly improved FMD, compared to baseline. The magnitude of FMD improvement was not different between CAE and hIAE (p=NS). Moreover, compared to baseline measurements, CAE (9.27±1.11m/sec vs. 8.17±1.48m/sec, p=0.003) and hIAE (9.14±1.07m/sec vs. 8.26±0.8m/sec, p&lt;0.001) improved fdPWV. Though, CAE and hIAE had no impact in cfPWV, compared to baseline measurements (p=NS for both). Finally, there was no significant difference in IL-17 levels after CAE [11(9-17) pg/ml vs. 16(12-22)pg/ml, p=0.23] and hIAE [12(9-17)pg/ml vs. 14(9-15)pg/ml, p=0.61], compared to baseline measurements. Conclusions: Both CAE and hIAE can favorably affect to a similar extent endothelial function suggesting another cardioprotective effect of exercise on atherosclerosis progression. Though, these types of aerobic exercise have a different impact on central and peripheral arterial stiffness. Whether both types of exercise exert similar long-term effects merits further investigation.

Functional and structural vascular adaptations following 8 weeks of low volume high intensity interval training in lower leg of type 2 diabetes patients and individuals at high risk of metabolic syndrome

We wished to investigate the effects of 8 weeks of low volume high intensity interval training (HIIT) on endothelial function of popliteal artery and circulating cell adhesion molecules in type 2 diabetes (T2D) patients and matched controls (CON). Methods: Over 8 weeks, non-active T2D patients and CONs cycled three times per week (10 × 60 sec HIIT). Pre- and post-HIIT measurements of endothelial function were conducted by applying flow-mediated dilation (FMD) along with taking venous blood samples. Results: Baseline diameter of popliteal artery increased significantly from an average of 5.53 mm to 5.97 mm (∼8%) in the CON-group (p = 0.006) and 5.32 mm to 5.61 mm (∼6%) in the T2D-group (p = 0.009). Peak diameter increased significantly from 5.82 mm to 6.36 mm (∼9%) in the CON-group (p = 0.001) and 5.57 mm to 5.93 mm (∼7%) in the T2D-group (p = 0.004). FMD% increased significantly from 5.12% to 6.58% in the CON-group (p = 0.004) and 4.84% to 5.66% in the T2D-group: (p = 0.045). The shear rate reduced significantly in both groups (CON-group: p = 0.04; T2D-group: p = 0.002). Circulating cell adhesion molecules remained unchanged (p > 0.05). Conclusion: HIIT induced an improvement of endothelium-dependent FMD and significant outwards artery modelling. No changes in circulating cell adhesion molecules were observed.

Effects of bariatric surgery on markers of subclinical atherosclerosis and endothelial function: a meta-analysis of literature studies.

Several studies confirmed a significantly increased carotid intima-media thickness (IMT) and impaired flow-mediated dilation (FMD) and nitrate-mediated dilation (NMD) in obese subjects, but few data are available on the effects of bariatric surgery on these markers of cardiovascular (CV) risk. We performed a meta-analysis of studies evaluating changes in IMT, FMD and NMD in obese patients after bariatric surgery. A systematic search was performed in the PubMed, Web of Science, Scopus and EMBASE databases without any language or publication year restriction. The last search was performed in January 2015. In addition, the reference lists of all retrieved articles were manually reviewed. Prospective studies evaluating the impact of bariatric surgery on the markers of CV risk were included. Changes in IMT, FMD and NMD after bariatric surgery were expressed as mean differences (MD) with pertinent 95% confidence intervals (95% CIs). IMT has been expressed in millimeters (mm); FMD and NMD as percentage (%). Impact of clinical and demographic features on effect size was assessed by meta-regression. Ten articles (314 obese patients) were included in the analysis. Six studies contained data on IMT (7 data sets; 206 patients), 8 studies on FMD (9 data sets; 269 patients) and 4 on NMD (4 data sets; 149 patients). After bariatric surgery, there was a significant reduction of IMT (MD: -0.17 mm; 95% CI: -0.290, -0.049; P=0.006) and a significant improvement in FMD (MD: 5.65%; 95% CI: 2.87, 8.03; P<0.001), whereas NMD did not change (MD: 2.173%; 95% CI: -0.796, 5.142; P=0.151). Interestingly, percentage of changes in the body mass index were associated with changes in IMT (Z=11.52, P<0.001), FMD (Z=-4.26, P<0.001) and NMD (Z=-3.81, P<0.001). Despite heterogeneity among studies, bariatric surgery is associated with improvement of subclinical atherosclerosis and endothelial function. These effects may significantly contribute to the reduction of the CV risk after bariatric surgery.

Exercise and Vascular Function in Child Obesity: A Meta-Analysis.

Conduit artery flow-mediated dilation (FMD) is a noninvasive index of preclinical atherosclerosis in humans. Exercise interventions can improve FMD in both healthy and clinical populations. This systematic review and meta-analysis aimed to summarize the effect of exercise training on FMD in overweight and obese children and adolescents as well as investigate the role of cardiorespiratory fitness (peak oxygen consumption [Vo2peak]) on effects observed. PubMed, Medline, Embase, and Cinahl databases were searched from the earliest available date to February 2015. Studies of children and/or adolescents who were overweight or obese were included. Standardized data extraction forms were used for patient and intervention characteristics, control/comparator groups, and key outcomes. Procedural quality of the studies was assessed using a modified version of the Physiotherapy Evidence Base Database scale. A meta-analysis involving 219 participants compared the mean difference of pre- versus postintervention vascular function (FMD) and Vo2peak between an exercise training intervention and a control condition. There was a significantly greater improvement in FMD (mean difference 1.54%, P < .05) and Vo2peak (mean difference 3.64 mL/kg/min, P < .05) after exercise training compared with controls. Given the diversity of exercise prescriptions, participant characteristics, and FMD measurement protocols, varying FMD effect size was noted between trials. Exercise training improves vascular function in overweight and obese children, as indicated by enhanced FMD. Further research is required to establish the optimum exercise program for maintenance of healthy vascular function in this at-risk pediatric population.

Effect of onion peel extract on endothelial function and endothelial progenitor cells in overweight and obese individuals

ObjectivesAcute or chronic intake of polyphenol-rich foods has been reported to improve endothelial function. Quercetin, found abundantly in onion, is a potent antioxidant flavonoid. The aim of this study was to investigate whether consumption of onion peel extract (OPE) improves endothelial function in healthy overweight and obese individuals. MethodsThis was a randomized double-blind, placebo-controlled study. Seventy-two healthy overweight and obese participants were randomly assigned to receive a red, soft capsule of OPE (100 mg quercetin/d, 50 mg quercetin twice daily; n = 36 participants) or an identical placebo capsule (n = 36) for 12 wk. Endothelial function, defined by flow-mediated dilation (FMD), circulating endothelial progenitor cells (EPCs) by flow cytometry, and laboratory test were determined at baseline and after treatment. ResultsBaseline characteristics and laboratory findings did not significantly differ between the two groups. Compared with baseline values, the OPE group showed significantly improved FMD at 12 wk (from 12.5 ± 5.2 to 15.2 ± 6.1; P = 0.002), whereas the placebo group showed no difference. Nitroglycerin-mediated dilation did not change in either group. EPC counts (44.2 ± 25.6 versus 52.3 ± 18.6; P = 0.005) and the percentage of EPCs were significantly increased in the OPE group. When FMD was divided into quartiles, rate of patients with endothelial dysfunction defined as lowest quartile (cutoff value, 8.6%) of FMD improved from 26% to 9% by OPE. ConclusionMedium-term administration of OPE an improvement in FMD and circulating EPCs.

Vascular and metabolic effects of ezetimibe combined with simvastatin in patients with hypercholesterolemia

BackgroundEzetimibe demonstrates decreasing visceral fat and improving insulin sensitivity (IS) in animals and humans. We first reported that simvastatin dose-dependently worsens insulin sensitivity. Whether ezetimibe may compensate untoward effects of simvastatin, depending on dosages of simvastatin has not been investigated in patients with hypercholesterolemia, compared with simvastatin alone. MethodsThis was a randomized, single-blind, placebo-controlled, parallel study. Fifty-one in each group were given placebo, ezetimibe 10mg combined with simvastatin 10mg (Vyto10), ezetimibe 10mg combined with simvastatin 20mg (Vyto20), or simvastatin 20mg alone (Simva20) daily for 2months. ResultsPlacebo, Vyto10, Vyto20, and Simva20 improved flow-mediated dilation relative to baseline measurements. Placebo therapy did not significantly change insulin and IS and adiponectin levels and visceral fat area (VFA) and VFA/subcutaneous fat area (SFA) relative to baseline measurements. Vyto10 therapy significantly decreased CRP and insulin levels and increased adiponectin levels and IS, and reduced VFA, VFA/SFA, and blood pressure. Vyto20 therapy did not significantly change insulin levels and IS and adiponectin levels but significantly reduced CRP levels and VFA, VFA/SFA, and blood pressure. Simva20 therapy significantly decreased adiponectin levels and IS but did not significantly change VFA, VFA/SFA, and blood pressure. Of note, these different effects of each therapy were significant by ANOVA. ConclusionsVyto10, Vyto20, and Simva20 showed significant reduction of LDL cholesterol levels and improvement of flow-mediated dilation in patients with hypercholesterolemia. However, Vyto10, Vyto20, and Simva20 showed significantly differential metabolic effects, depending on dosages of simvastatin.

Vascular and Metabolic Effects of Ezetimibe Depend on Dosages of Simvastatin in Patients with Hypercholesterolemia

Background: Ezetimibe demonstrates decreasing visceral fat and improving insulin sensitivity in animals and humans. We first reported simvastatin dose-dependently worsens insulin sensitivity. Whether ezetimibe may compensate untoward effects of simvastatin, depending on dosages of simvastatin have not been investigated in patients with hypercholesterolemia, compared with simvastatin alone. Methods: This was a randomized, single-blind, placebo-controlled, parallel study. Age, sex, and body mass index were matched among groups. Fifty-one in each group were given placebo, ezetimibe 10 mg combined with simvastatin 10 mg (Vyto10), ezetimibe 10 mg combined with simvastatin 20 mg (Vyto20), or simvastatin 20 mg alone (Simva20), respectively daily for 2 months. Results: Placebo therapy did not significantly change insulin and insulin sensitivity and adiponectin levels and visceral fat area (VFA) and VFA/subcutaneous fat area (SFA) relative to baseline measurements. Vyto10 therapy significantly decreased CRP and insulin levels and increased adiponectin levels and insulin sensitivity, and reduced VFA, VFA/SFA, and blood pressure. Vyto20 therapy did not significantly change insulin levels and insulin sensitivity and adiponectin levels but significantly reduced CRP levels and VFA, VFA/SFA, and blood pressure. Simva20 therapy significantly decreased adiponectin levels and insulin sensitivity but did not significantly change VFA, VFA/SFA, and blood pressure. Of note, these different effects of each therapy were significant by ANOVA. Conclusions: Vyto10, Vyto20, and Simva20 showed significant reduction of LDL cholesterol levels and improvement of flow-mediated dilation in patients with hypercholesterolemia. However, Vyto10, Vyto20, and Simva20 showed significantly differential metabolic effects, depending on dosages of simvastatin.

MP43-20 ENDOTHELIAL DYSFUNCTION IN PATIENTS OF ERECTILE DYSFUNCTION USING SHORT-TERM LOW DOSE TADALAFIL : A DOUBLE BLIND RANDOMIZED CONTROL TRIAL

You have accessJournal of UrologySexual Function/Dysfunction/Andrology: Evaluation I1 Apr 2015MP43-20 ENDOTHELIAL DYSFUNCTION IN PATIENTS OF ERECTILE DYSFUNCTION USING SHORT-TERM LOW DOSE TADALAFIL : A DOUBLE BLIND RANDOMIZED CONTROL TRIAL Ravimohan Mavuduru, Pawan Kundal, Smita Pattanaik, Shrawan Singh, and Arup Mandal Ravimohan MavuduruRavimohan Mavuduru More articles by this author , Pawan KundalPawan Kundal More articles by this author , Smita PattanaikSmita Pattanaik More articles by this author , Shrawan SinghShrawan Singh More articles by this author , and Arup MandalArup Mandal More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.1627AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Flow mediated dilatation (FMD) of brachial artery is a noninvasive measurement of Endothelial dysfunction EnD. Studies have shown low dose Tadalafil improves (EnD), however placebo controlled RCTs are lacking. METHODS This DB-RCT was conducted in accordance with the principles of Declaration of Helsinki and was approved by Institutional Ethics Committee. ED and EnD were assessed by self-administered IIEF-5 questionnaire and FMD respectively at baseline and 4 weeks by the same observer. Patients with FMD of < 15% were included. patients with history of PDEI intake in the past were excluded. Patients were randomized in 1:1 ratio to receive either placebo or tadalafil by a computer generated randomization list. Both placebo and tadalafil in tablet form were dispensed in bottles with dosage for 4weeks by a co-investigator who was not involved in the process of selection or evaluation of the end points to ensure complete blinding. Compliance was assessed by checking the empty drug bottles. Any drug related events during the study were recorded. The randomization codes were decoded at study completion. Appropriate statistical tests were applied. RESULTS Of 96 patients, 89 were randomized, and 82 completed the study, 41 in each group. Demographic profile, baseline IIEF-5 score and FMD % were comparable. Post-treatment there were significant improvements in IIEF-5 score (Pre vs Post treatment; Tadalafil: - 11.4±3.2vs 15.9±3.7, p <0.001 and placebo: 11.2±3.2 vs 14.9±3.5, p <0.001, respectively ) and FMD % (Pre vs Post treatment; Tadalafil: 11.2±2.2 vs 13.8±2.7, p <0.001 and placebo: 11.6±1.7vs 14.0±2.7, p <0.001, respectively) and this change was significant in all the sub-groups (based on IIEF-5 severity categorization). Inter-group comparison did not show any significant difference in IIEF scores (Mean change in IIEF-5 scores, Tadalafil vs Placebo: 3.7±1.9 vs 4.4 ± 3.3, p=0.223) and FMD % (Mean change in FMD%, Tadalafil vs Placebo: 2.4 ± 2.6 and 2.8 ± 2.9, p=0.528) This was true across all the subgroups except in patients with severe ED, where tadalafil group showed a significant improvement in FMD %.( Mean change in FMD%, Tadalafil vs Placebo: 4.6 ± 1.9 vs 1.6 ± 1.4, p=0.020 ). The adverse events were significantly more in Tadalafil group (Tadalafil vs placebo 14 ADR vs 5 ADR, p<0.001) CONCLUSIONS The response of low dose tadalafil (10mg per day) on IIEF and FMD is largely similar to placebo especially in young patients, however to draw meaningful conclusions, utility of FMD % in young patients and placebo effect a longer study need to be seen. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e525-e526 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ravimohan Mavuduru More articles by this author Pawan Kundal More articles by this author Smita Pattanaik More articles by this author Shrawan Singh More articles by this author Arup Mandal More articles by this author Expand All Advertisement Advertisement PDF DownloadLoading ...

Endothelial dysfunction and oxidative stress in children with sleep disordered breathing: Role of NADPH oxidase

ObjectiveOxidative stress plays a crucial role in impairing endothelial function in sleep disordered breathing (SDB) but the underlying mechanism is still undefined. The objective of this study was to evaluate the interplay between oxidative stress, assessed by serum isoprostanes (8-iso-PGF2α) and soluble NOX2-dp (sNOX2-dp), and endothelial function, assessed by flow-mediated dilation (FMD), in children with SDB and healthy controls (HC). MethodsOne-hundred forty-four children including 45 with primary snoring (PS), 22 with obstructive sleep apnea (OSA) and 67 HC were recruited in this study; in 15 out of 22 OSA children FMD, serum 8-iso-PGF2α and sNOX2-dp were assessed before and after one month post adeno-tonsillectomy (AT). ResultsCompared with HC, OSA and PS children had significantly higher sNOX2-dp and serum 8-iso-PGF2α levels and lower FMD; compared with PS, FMD was significantly lower in OSA children. No significant difference for sNOX2-dp and serum 8-iso-PGF2α was observed between OSA and PS children. FMD was inversely correlated with sNOX2-dp levels (p < 0.001) and with serum 8-iso-PGF2α (p < 0.001). In multiple linear regression analysis, sNOX2-dp (p < 0.001) and serum 8-iso-PGF2α (p < 0.001) were the only independent predictive variables associated with FMD.AT significantly decreased sNOX2-dp and serum 8-iso-PGF2α levels (from 38.2 ± 8.8 to 22.4 ± 11.1 pg/ml, p < 0.001, and from 281.4 ± 69.7 to 226.0 ± 66.4 pg/ml, p < 0.001, respectively); conversely, FMD significantly increased after AT in OSA children (from 3.0 ± 1.5 to 8.0 ± 2.8%, p < 0.001). ConclusionThis study suggests that NOX2-derived oxidative stress is involved in artery dysfunction in SDB children. Such hypothesis is reinforced by FMD improvement after AT coincidentally with oxidative stress lowering. Clinical Trial RegistrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT02247167.

Daily consumption of red grape cell powder in a dietary dose improves cardiovascular parameters: a double blind, placebo-controlled, randomized study

Consumption of polyphenol-rich food and food ingredient such as grape and grape products improved various cardiovascular parameters. In this study, we investigate the effect of dietary daily consumption of red grape cell powder (RGC) on blood pressure (BP) and flow-mediated dilatation (FMD) as well as on oxidative stress in 50 subjects with prehypertension and mild hypertension. The subjects were randomized into groups that consumed 200, 400 mg RGC or placebo daily for 12 weeks. RGC consumption was associated with an improvement of FMD (p = 0.013). There was a significant decrease in lipid peroxidation (p = 0.013) after 12 weeks in a combined RGC-treated group. The diastolic BP decreased significantly in the 200 mg RGC group compared to the placebo group (p = 0.032). Our results indicate that a daily supplementation, of red grape cell powder, for 12 weeks affects endothelial function, diastolic BP and oxidative stress without any adverse effects.

Cocoa consumption dose-dependently improves flow-mediated dilation and arterial stiffness decreasing blood pressure in healthy individuals.

Cocoa flavonoids exert beneficial vascular effects and reduce the risk of cardiovascular morbidity and mortality. Nevertheless, the involved mechanisms have not been clarified and no study has yet focused on the dose-response effects. We aimed to investigate the effects of different doses of cocoa flavonoids on flow-mediated dilation (FMD), endothelin-1 (ET-1), pulse wave velocity (PWV), and SBP and DBP. According to a randomized, double-blind, controlled, cross-over design, 20 healthy volunteers (1.5% improvement in FMD in 20 individuals: 0.99 at alpha = 0.05) were assigned to receive either five treatments with daily intake of 10 g cocoa (0, 80, 200, 500 and 800 mg cocoa flavonoids/day) in five periods lasting 1 week each. Cocoa dose-dependently increased FMD from 6.2% (control) to 7.3, 7.6, 8.1 and 8.2% after the different flavonoid doses, respectively (P < 0.0001). Compared with the control, even 80 mg cocoa flavonoids per day increased FMD (P < 0.0001). Cocoa dose-dependently decreased PWV (P < 0.0001). Cocoa intake decreased office blood pressure (BP) (SBP: -4.8 ± 1.03 mmHg, P < 0.0001; DBP: -3.03 ± 1.07 mmHg, P = 0.0011). With respect to control, cocoa ingestion decreased 24-h (P = 0.05) and daytime (P = 0.038) SBP, and 24-h (P = 0.0064), daytime (P = 0.0088) and night-time (P = 0.0352) pulse pressure. Compared with the control, cocoa dose-dependently decreased ET-1 levels [from 17.1 (control) to 15.2, 14.5, 14.2 and 14.1 pg/ml, after the different flavonoid doses, respectively (P for treatment <0.05)]. Compared with the control, significant changes were observed for all doses of flavonoids (ET-1; P < 0.05). Our study showed for the first time that cocoa dose-dependently improved FMD and decreased PWV and ET-1 also by ameliorating office and monitored BP. Our findings are clinically relevant, suggesting cocoa, with very low calorie intake, might be reasonably incorporated into a dietary approach, representing a consistent tool in cardiovascular prevention.

Exercise modalities and endothelial function: a systematic review and dose-response meta-analysis of randomized controlled trials.

Regular exercise is associated with enhanced nitric oxide (NO) bioavailability. Flow-mediated dilation (FMD) is used widely to assess endothelial function (EF) and NO release. The aims of this systematic review and meta-analysis were to (i) investigate the effect of exercise modalities (aerobic, resistance or combined) on FMD; and (ii) determine which exercise and participant characteristics are most effective in improving FMD. We searched the MEDLINE, Embase, Cochrane Library, and Scopus databases for studies that met the following criteria: (i) randomized controlled trials of exercise with comparative non-exercise, usual care or sedentary groups; (ii) duration of exercise intervention ≥4 weeks; (iii) age ≥18 years; and (iv) EF measured by FMD before and after the intervention. Weighted mean differences (WMDs) with 95% confidence interval were entered into a random effect model to estimate the pooled effect of the exercise interventions. All exercise modalities enhanced EF significantly: aerobic (WMD 2.79, 95% CI 2.12-3.45, p = 0.0001), resistance (WMD 2.52, 95% CI 1.11-3.93, p = 0.0001) and combined (WMD 2.07, 95% CI 0.70-3.44, p = 0.003). A dose-response relationship was observed between aerobic exercise intensity and improvement in EF. A 2 metabolic equivalents (MET) increase in absolute exercise intensity or a 10% increase in relative exercise intensity resulted in a 1% unit improvement in FMD. There was a positive relationship between frequency of resistance exercise sessions and improvement in EF (β 1.14, CI 0.16-2.12, p = 0.027). All exercise modalities improve EF significantly and there was a significant, positive relationship between aerobic exercise intensity and EF. Greater frequency, rather than intensity, of resistance exercise training enhanced EF.

Therapy of endocrine disease. Effects of chronic use of phosphodiesterase inhibitors on endothelial markers in type 2 diabetes mellitus: a meta-analysis.

Diabetes mellitus (DM) is associated with endothelial dysfunction, reducing nitric oxide-dependent vasodilation, and increasing production of pro-inflammatory factors, leading to an increased risk of long-term cardiovascular disease. As the effects of phosphodiesterase 5 inhibitors (PDE5i) on endothelial function have not been systematically investigated, we conducted a meta-analysis of available randomized clinical trials (RCTs). A thorough search of the literature was carried out. Relevant studies were considered according to RCT study design, enrollment of men with type 2 DM, chronic administration of PDE5i, and evaluation of endothelial function through both hemodynamic and endothelial inflammation-related parameters. Fifteen studies fulfilled the eligibility criteria but only six RCTs met the inclusion criteria and were analyzed for 476 diabetic men, 239 randomized to Sildenafil, and 237 to placebo respectively. Four RCTs evaluated flow-mediated dilation (FMD), demonstrating a weighted mean increase of 2.19% (95% CI 0.48 to 3.90). This result showed a high heterogeneity (I(2): 98%). Thus, a further sub-group meta-analysis was performed and this analysis confirmed a significant, Sildenafil-related FMD improvement. Sildenafil improved endothelin 1 and high sensitivity C-reactive protein by ∼-0.94 pg/ml and -0.36 mg/l, respectively, not reaching statistical significance (P=0.69 and P=0.22 respectively). Finally, Sildenafil administration significantly reduced serum levels of interleukin 6 (IL6, -0.82 pg/ml; 95% CI -1.58 to -0.07). This meta-analysis suggests a beneficial effect of chronic PDE5i administration on endothelial function. Chronic Sildenafil administration seems to improve hemodynamic (FMD) and serum pro-inflammatory makers (IL6) in diabetic men. Larger studies are needed to confirm the effects of chronic PDE5i on endothelial function.