Baseline Flow-mediated Dilation Research Articles

Effects of SGLT-2i and GLP-1RA in vascular function parameters: the impact of the weight loss

Abstract Background Arterial stiffness and endothelial function markers flag increased cardiovascular disease risk in patients with type 2 Diabetes Mellitus (T2DM), while weight management plays a crucial role for the management of glycemic control and prevention of complications in these patients. Purpose To investigate the effects of novel antidiabetic agents on arterial stiffness and endothelial function as well as the metabolic parameters of HbA1c and Weight in T2DM patients. Patients and Methods: We enrolled 99 consecutive patients under stable antidiabetic therapy who did not reach therapeutic targets. Subjects were assessed to receive an additional antidiabetic agent to optimize glucose control; glucagon like peptide-1 receptor agonist (GLP-1RA, n=50) or sodium/glucose cotransporter-2 inhibitor (SGLT-2i, n=49). Glycosylated hemoglobin (Hba1c) and weight expressed through Body Mass Index (BMI) along with carotid-femoral pulse wave velocity (PWV) and flow-mediated dilatation (FMD), as biomarkers of arterial stiffness and endothelial function accordingly, were measured at baseline and 3 months after treatment intensification. Results There were no differences between the study groups in traditional risk factors of age and sex or baseline HbA1c, BMI, PWV, and FMD levels (ps=NS for all). In both groups PWV values displayed a statistically significant improvement from 11.2±2.5 to 9.3±2.2 m/sec (p<0.001) in the GLP-1RA group and from 10.7±2.4 to 8.9±2.0 m/sec (p=0.001) in the SGLT-2i group, as presented in Figure 1 through the differences in the values of PWV. FMD values were also significantly improve in both groups from baseline to follow-up; from 6.04±1.22 to 6.50±1.26% (p<0,001) for the GLP-1RA group and from 6.38±1.21 to 6.81±1.29% (p<0.001) for the SGLT-2i group. Moreover, both groups achieved better weight management goals in terms of BMI values between baseline and follow-up; from 33.6±4.9 to 31.5±4.6 kg/m2 for the GLP-1RA group (p<0.001) and from 31.8±5.5 to 30.5±5.6 kg/m2 for the SGLT-2i group (p<0.001), in addition to achieving better glycemic control in terms of HbA1c values, as seen in their paired differences: for GLP-1RA: 1.3±0.7% and for SGLT-2i: 0.8±0.5%. Interestingly, in the SGLT-2i group the magnitude of the PWV improvement was correlated with the weight loss (r=0.368, p=0.007). Conclusion These data provide evidence that the newer antidiabetic drugs, both GLP1-RA and SGLT-2i, have actions that benefit both vascular function, endothelium as well as metabolic parameters. Interestingly, in the patients receiving SGLT-2i the magnitude of the PWV improvement was correlated with the weight loss.delta PWV for SGLT-2i & GLP-1RA groupsCorrelation of deltaWeight & deltaPWV

Empagliflozin and Dapagliflozin Improve Endothelial Function in Mexican Patients with Type 2 Diabetes Mellitus: A Double-Blind Clinical Trial.

To assess the acute effect of empagliflozin versus dapagliflozin administration on flow-mediated vasodilation in patients with type 2 diabetes mellitus. A double-blind clinical trial, at the Experimental and Clinical Therapeutics Institute, University Health Sciences Center, at the Universidad de Guadalajara, in inpatients with T2D according to the 2023 ADA criteria. Thirty patients (15 males and 15 females), aged between 35 and 65 years, were included in this study, according to the 2023 ADA criteria. The eligible patients were randomly assigned to three groups: empagliflozin 25 mg once daily, dapagliflozin 10 mg once daily, or placebo once daily. Anthropometric parameters were taken using validated techniques. FMD was measured using a high-resolution semiautomatic ultrasound UNEX-EF 38G (UNEX Co., Ltd., Nagoya, Japan). Arterial tension was determined with the OMRON electronic digital sphygmomanometer (HEM 907 XL, Kyoto, Japan). The group of patients who received empagliflozin had a significantly lower baseline flow-mediated dilation (FMD) compared to the group receiving dapagliflozin (p = 0.017); at the end of this study, the empagliflozin group achieved a comparable FMD to the dapagliflozin group (p = 0.88). After the treatment period, the empagliflozin and dapagliflozin groups achieved similar FMD, suggesting a class effect.

INTRAVENOUS IMMUNOGLOBULINS LEAD TO FUNCTIONAL VASCULAR AMELIORATION IN LONG-COVID

Objective: The Long-COVID syndrome constitutes a major physical and psychological challenge for many patients after the recovery from COVID-19. We have previously shown positive effects of intravenous immunoglobulins (IVIG) on multiple symptoms. The effect of this therapeutical approach on vascular function and different levels of disease burden remains elusive. Design and method: We performed a prospective study, enrolling 21 patients with diagnosed Long-COVID, who received 3 monthly courses of IVIG (0.5 g/kg Privigen, CSL Behring, Austria) alongside supportive therapy (group 1). The control group (group 2; n=29) was addressed by supportive therapy, only. The study population was homogeneous for age, comorbidities and time since SARS-CoV-2 infection. We assessed vascular endothelial function by flow mediated dilation (FMD). Long-COVID associated fatigue intensity, related disability and quality of life were assessed by Short Form Health Survey-36, Chalder and Bell scale. Neuropsychological assessments utilized the German version of the ’Consortium to Establish a Registry for Alzheimer's Disease Neuropsychological Assessment Battery’ (CERAD-Plus). Results: The median FMD at baseline in group 1 was 5.0% (interquartile range [IQR] 4.2-6.1%). We saw a substantial amelioration (+27%) of FMD after IVIG, reaching a median of 6.6% (IQR 4.5-9.4%; p=0.039). Baseline FMD in the comparison group was 5.2% (IQR 3.5-7.6%), supportive treatment resulting in unsignificant increase (FMD 6.1% [IQR 4.6-7.7%; p=0.177). Baseline CERAD-Plus scores were comparable between groups (p=0.280). Only treatment with IVIG resulted in a relevant amelioration of neurocognition (p=0.05; group 2 p=0.430). Furthermore, less Fatigue (Chalder Fatigue scale bimodal and Likert p=0.002, each) and disability was seen after 3 months of IVIG (Bell Score, p=0.008), supportive treatment did not ameliorate this burden (Chalder Fatigue Scale bimodal p=0.086 and Likert p=0.952; Bell Score p=0.121). Health related quality of life (SF-36) increased for both groups (group 1 p=0.003, group 2 p=0.017). Conclusions: Using a broad test battery, addressing neuropsychological function, fatigue, related disability and health related quality of life as well as vascular function, we were able to confirm the potential beneficial effect of IVIG in Long-COVID. IVIG might be a candidate approach in this context, that requires further evaluation in randomized controlled trials.

Peripheral vascular function in stroke: systematic review and meta-analysis.

Peripheral vascular dysfunction, measured as flow-mediated dilation (FMD), is present across all phases of stroke recovery and elevates the risk for recurrent cardiovascular events. The objective of this systematic review and meta-analysis was to characterize baseline FMD in individuals' poststroke, with consideration for each phase of stroke recovery. Three databases (PubMed, CINAHL, and Embase) were searched between January 1, 2000 and October 12, 2023 for studies that examined baseline FMD in stroke. Three reviewers conducted abstract and full-text screening, data extraction, and quality assessment. A random effects model was used to estimate FMD across studies. Meta-regression was used to examine the impact of age and time since stroke (acute, subacute, chronic) on FMD. Twenty-eight studies with ischemic and hemorrhagic stroke were included. Descriptive statistics for the demographics and FMD values of each study are presented. For the meta-analysis, average estimate FMD was 3.9% (95% CI: 2.5-5.3%). We report a large amount of heterogeneity (Cochrane's Q P value <0.001, and I2 = 99.6%). Differences in average age and the time poststroke between studies were not significantly associated with differences in FMD values. Despite the large heterogeneity for FMD values across studies, our primary finding suggests that FMD remains impaired across all phases of stroke.NEW & NOTEWORTHY This systematic review and meta-analysis offers invaluable insight into poststroke vascular function. Despite the inherent heterogeneity among the 28 studies analyzed, we report that peripheral vascular dysfunction, as quantified by flow-mediated dilation, exists across all stages of stroke recovery. This finding underscores the importance for interventions that focus on improving vascular health and secondary stroke prevention.

Relationship of Warfarin and Apixaban with Vascular Function in Patients with Atrial Fibrillation

Introduction: Atrial fibrillation (AF) is associated with endothelial damage/dysfunction. Herein, we tested the hypothesis that brachial artery flow-mediated dilation (FMD) is superior in AF patients taking apixaban compared to warfarin. Methods: AF patients on apixaban (n = 46; 67 [7] years; mean [standard deviation]; 15 women) and warfarin (n = 27; 73 [9] years (p < 0.01); 11 women) were recruited. Duplex Doppler ultrasound imaging was undertaken during baseline (2 min), cuff inflation (5 min), and following cuff deflation (3 min). FMD was defined as peak increase in brachial artery diameter following cuff deflation and analysed as percentage change in diameter, as a ratio of FMD, shear rate area under the curve (SR_AUC; FMD-to-SR_AUC), and using SR_AUC as a covariate (FMD_SR). Results: Baseline artery diameter (4.96 [1.14] vs. 4.89 [0.88] mm), peak diameter (5.12 [1.17] vs. 5.14 [0.93] mm), and FMD_SR (3.89 [3.62] vs. 4.80 [3.60] %) were not different between warfarin and apixaban (p > 0.05; analysis of covariance with age, CHA₂DS₂-VASc, years since AF diagnosis, number of diabetics, alcohol drinkers, and units of alcohol consumed per week as covariates). Stepwise multiple regression identified independent association of fibrillation, hypertension, and increased age with FMD. Conclusion: AF patients on warfarin and apixaban exhibit similar endothelium-dependent vasodilation. Increased blood pressure negatively impacts vasodilator capacity in AF patients.

Influence of enhanced external counterpulsation on endothelial function: a meta-analysis of randomized controlled trials

Objectives Enhanced external counterpulsation (EECP) is an effective and noninvasive treatment for patients with refractory angina and chronic heart failure. However, previous studies evaluating the influence of EECP on endothelial function showed inconsistent results. This systematic review and meta-analysis was conducted to evaluate the effects of EECP on endothelial function measured by brachial artery flow-mediated dilation (FMD). Design PubMed, Embase, Cochrane Library, CNKI, and Wanfang databases were searched for randomized controlled trials comparing the influence of EECP versus usual care on FMD in adult population. A random-effects model incorporating the potential influence of heterogeneity was used to pool the results. Results Nineteen studies with 1647 patients were included in the meta-analysis. Compared with usual care or conventional therapy, additional treatment with EECP for 3–7 weeks was associated with a significantly improved FMD (mean difference [MD]: 1.96%, 95% confidence interval [CI]: 1.57–2.36, p < 0.001, I 2 = 52%). Subgroup analysis showed consistent results in patients with coronary artery disease and in patients with other diseases (p for subgroup difference = 0.21). Results of meta-regression analysis showed that the mean baseline FMD level was positively correlated with the influence of EECP on FMD (coefficient = 0.42, p < 0.001). Results of subgroup analysis suggested that the increment of FMD following EECP was larger in patients with baseline FMD ≥ 5% (MD: 2.69, 95% CI: 2.27–3.10, p < 0.001; I 2 = 15%) compared to those with baseline FMD < 5% (MD: 1.49, 95% CI: 1.13–1.85, p < 0.001; I 2 = 0%; p for subgroup difference < 0.001). Conclusions EECP may be effective in improving endothelial function measured by FMD.

Impact of bariatric surgery on carotid intima-media thickness, flow-mediated dilation, and nitrite-mediated dilation: a systematic review and meta-analysis.

Obesity is considered one of the independent risk factors for atherosclerosis and is strongly correlated with cardiovascular morbidity and mortality. Previous studies showed carotid intima-media thickness (CIMT), flow-mediated dilation (FMD), and nitrite-mediated dilatation (NMD) are reliable non-invasive markers of arterial damage and dysfunction. The aim of this study was to evaluate the effect of bariatric surgery on CIMT, FMD, and NMD markers in patients with obesity. A systematic search was performed in the PubMed, Embase, Scopus, and Web of Science databases until May 2022. All the English-published studies on the effect of bariatric surgery on CIMT, FMD, and NMD were included. A quantitative meta-analysis was performed, as well as subgroup analyses for the type of procedure and duration of follow-up. Meta-analysis of 41 studies with 1639 patients showed CIMT was significantly reduced by .11 mm after bariatric surgery (95% CI, -.14 to -.08; P < .001; mean follow-up = 10.8 mo). The pooled analysis of 23 studies with 1106 patients showed an increase of FMD by 4.57% after bariatric surgery (95% CI, 2.69-6.44; P < .001; mean follow-up = 11.5 mo). The results of a pooled analysis of 12 studies with 346 patients showed a significant increase of NMD by 2.46% after bariatric surgery (95% CI, .99-3.94; P < .001; mean follow-up = 11.4 mo). The random effect meta-regression demonstrated that baseline CIMT and FMD significantly affect the changes in CIMT and FMD. This meta-analysis showed bariatric surgery can improve CIMT, FMD, and NMD markers in patients with obesity. These improvements show the known effect of metabolic surgery in decreasing cardiovascular risk.

Menopausal stage differences in endothelial resistance to ischemia-reperfusion injury.

In postmenopausal women, reduced ovarian function precedes endothelial dysfunction and attenuated endothelial resistance to ischemia-reperfusion (IR) injury. We hypothesized that IR injury would lower endothelial function, with premenopausal women demonstrating the greatest protection from injury, followed by early, then late postmenopausal women. Flow-mediated dilation (FMD) was assessed at baseline and following IR injury in premenopausal (n = 11), early (n = 11; 4 ± 1.6 years since menopause), and late (n = 11; 15 ± 5.5 years since menopause) postmenopausal women. There were significant group differences in baseline FMD (p = 0.007); post hoc analysis revealed a similar resting FMD between premenopausal (7.8% ± 2.1%) and early postmenopausal (7.1% ± 2.7%), but significantly lower FMD in late postmenopausal women (4.5% ± 2.3%). Results showed an overall decline in FMD after IR injury (p < 0.001), and a significant condition*time interaction (p = 0.048), with early postmenopausal women demonstrating the most significant decline in FMD following IR. Our findings indicate that endothelial resistance to IR injury is attenuated in healthy early postmenopausal women.

Vascular Function and Intima-Media Thickness in Children and Adolescents with Growth Hormone Deficiency: Results from a Prospective Case-Control Study

Introduction: Growth hormone deficiency (GHD) may be associated with subtle cardiovascular abnormalities, reversible upon starting GH treatment. Data on vascular morphology and function in GHD children are scanty and inconclusive. The aim of our study was to evaluate the effects of GHD and GH treatment on endothelial function and intima-media thickness (IMT) in children and adolescents. Methods: We enrolled 24 children with GHD (10.85 ± 2.71 years) and 24 age-, sex-, and BMI-matched controls. We evaluated anthropometry, lipid profile, asymmetric dimethylarginine (ADMA), brachial flow-mediated dilatation (FMD), and IMT of common (cIMT) and internal (iIMT) carotid artery at study entry in all subjects and after 12 months of treatment in GHD children. Results: At baseline GHD, children had higher total cholesterol (163.17 ± 18.66 vs. 149.83 ± 20.68 mg/dL, p = 0.03), LDL cholesterol (91.18 ± 20.41 vs. 77.08 ± 19.73 mg/dL, p = 0.019), atherogenic index (AI) (2.94 ± 0.71 vs. 2.56 ± 0.4, p = 0.028), and ADMA (215.87 ± 109.15 vs. 164.10 ± 49.15 ng/mL, p < 0.001), compared to controls. GHD patients also exhibited increased higher waist-to-height ratio (WHtR) compared to controls (0.48 ± 0.05 vs. 0.45 ± 0.02 cm, p = 0.03). GH therapy resulted in a decrease in WHtR (0.44 ± 0.03 cm, p = 0.001), total (151.60 ± 15.23 mg/dL, p = 0.001) and LDL cholesterol (69.94 ± 14.40 mg/dL, p < 0.0001), AI (2.28 ± 0.35, p = 0.001), and ADMA (148.47 ± 102.43 ng/mL, p < 0.0001). GHD showed lower baseline FMD than controls (8.75 ± 2.44 vs. 11.85 ± 5.98%, p = 0.001), which improved after 1-year GH treatment (10.60 ± 1.69%, p = 0.001). Baseline cIMT and iIMT were comparable between the two groups, but slightly reduced in GHD patients after treatment. Conclusion: GHD children may exhibit endothelial dysfunction in addition to other early atherosclerotic markers like visceral adiposity, and altered lipids, which can be restored by GH treatment.

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.

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.

Effect of Daily Avocado Intake for Six Months on Flow-Mediated Dilation: A Sub-Study of the Habitual Diet and Avocado Trial, a Randomized Controlled Study

ObjectivesThe Habitual diet and Avocado Trial (HAT), a multicenter parallel randomized controlled trial, was designed to examine the health effects of consuming 1 avocado per day for 6-months compared to a habitual diet limited in avocados in individuals with abdominal obesity. We assessed the effects of the intervention on endothelial function using flow-mediated dilation (FMD) of the brachial artery. MethodsAll participants were ≥25 years of age with an elevated waist circumference (≥88 cm women; ≥102 cm men). Participants were randomized into either a control group (HD: consumed <2 avocados/month for 6 months) or an experimental group (AVO: consumed 1 avocado/day for 6 months). At the Pennsylvania State University, University Park site (n = 134), FMD was measured at baseline and end of the study. Within-person change scores were calculated by subtracting FMD at baseline from FMD at the end of the study. Linear regression was used to examine between-group differences in change across 6 months. ResultsThe sample was 78% female (BMI 33 ± 5 kg/m2). At baseline, FMD was 7.73 ± 3.37% in the AVO group, and 6.85 ± 2.67% in the HD group. FMD decreased by –0.10 ± 2.94% in the AVO group and increased by 0.52 ± 3.17% in the HD group. There were no significant between-group differences in 6-month change in FMD (0.62%, 95%CI = –0.46–1.70, p = 0.26). The results remained unchanged after adjustment for sex, BMI, and baseline FMD (0.15%, 95%CI = –0.77–1.06, p = 0.75). ConclusionsResults suggest that consumption of 1 avocado per day for 6 months in adults with abdominal obesity is not associated with a significant improvement in endothelial function, compared to adults following their habitual diet. Participants in this study had relatively high FMD at baseline, which may have reduced our ability to observe improvements in endothelial function. Funding SourcesAvocado Nutrition Center and the National Center for Advancing Translational Sciences, National Institutes of Health (1UL1TR002014-01)

The effects of dietary nitrate supplementation in post‐menopausal women: Does timing matter?

There is a need for low risk, non‐estrogen therapies for cardiovascular disease prevention in post‐menopausal women, a population expected to reach 1.2 billion worldwide by 2030. Consumption of beetroot juice and other nitrate‐rich products (green leafy vegetables, supplements) is a promising non‐pharmaceutical strategy for increasing circulating nitric oxide levels and improving vascular function in post‐menopausal women. Whether time since menopause (reproductive age) influences the vasoprotective effects (arterial stiffness and endothelial function) of dietary nitrate supplementation has not been established.PURPOSETo determine the vascular protective mechanisms and efficacy of a nitric oxide boosting supplement (beetroot juice) in women at two post‐ menopausal stages (early‐ vs late‐post menopause).METHODSEarly‐ (1‐6 years following their final menstrual cycle, n=5) and late‐ (n=10) postmenopausal women consumed nitrate‐rich (300 mg/70 mL) and nitrate‐depleted beet root juice acutely and for 7 days. Percent brachial artery flow‐mediated dilation (FMD) was measured at baseline, acutely (90 minutes post‐BRJ consumption), and 15‐minutes and 30‐minutes after 20‐minute upper arm ischemia‐reperfusion (IR) injury for each drink. Brachial‐ankle pulse wave velocity (baPWV) was measured pre‐ and post‐ 7‐day supplementation.RESULTSDue to the nature of this double‐blind trial, data presented are from the baseline (pre‐juice consumption) visit only. Significant (p&lt;0.05) group differences were observed for baseline PWV (early = 1158+115 cm/s; late = 1469+296 cm/s) and FMD at the 30‐minute post‐IR injury timepoint (early = 8.4+4.6%; late = 5.8+2.7%). No group differences were observed in FMD responses at rest (p=0.2) or 15 minutes post‐IR injury (p=0.4).CONCLUSIONThese preliminary results suggest that time since menopause negatively influences arterial stiffness and may prolong recovery from endothelial IR injury in women.

Impact of angiotensin receptor-neprilysin inhibition on vascular function in heart failure with reduced ejection fraction: A pilot study.

The mechanisms for the benefits of Angiotensin Receptor Neprilysin Inhibition (ARNi) in heart failure patients with reduced ejection fraction (HFrEF) are likely beyond blood pressure reduction. Measures of vascular function such as arterial stiffness and endothelial function are strong prognostic markers of cardiovascular outcomes in HFrEF, yet the impact of ARNi on vascular health remains to be explored. We hypothesized that arterial stiffness and endothelial function would improve after 12 weeks of ARNi in HFrEF. We tested 10 stable HFrEF patients at baseline and following 12 weeks of ARNi [64 ± 9 years, Men/Women: 9/1, left ventricular ejection fraction (EF): 28 ± 6%] as well as 10 stable HFrEF patients that remained on conventional treatment (CON: 60 ± 7 years, Men/Women: 6/4, EF: 31 ± 5%; all p = NS). Arterial stiffness was assessed via carotid‐femoral pulse wave velocity (PWV) and endothelial function was assessed via brachial artery flow‐mediated dilation (FMD). PWV decreased after 12 weeks of ARNi (9.0 ± 2.1 vs. 7.1 ± 1.2 m/s; p < 0.01) but not in CON (7.0 ± 2.4 vs. 7.5 ± 2.3 m/s; p = 0.35), an effect that remained when controlling for reductions in mean arterial pressure (p < 0.01). FMD increased after 12 weeks of ARNi (2.2 ± 1.9 vs. 5.5 ± 2.1%; p < 0.001) but not in CON (4.8 ± 3.8 vs. 5.4 ± 3.4%; p = 0.34). Baseline PWV (p = 0.06) and FMD (p = 0.07) were not different between groups. These preliminary data suggest that 12 weeks of ARNi therapy may reduce arterial stiffness and improve endothelial function in HFrEF. Thus, the findings from this pilot study suggest that the benefits of ARNi are beyond blood pressure reduction and include improvements in vascular function.

An observational study of the endothelial dysfunction in type 2 diabetes mellitus and its association with risk factors

Background: Cardiovascular diseases (CVDs) are the major culprit to cause morbidity in type 2 diabetes mellitus (T2DM) patients. Endothelial dysfunction (ED) precedes the progressed stage of CVD presentation. This study aimed to study the risk factors for ED and identify the modifiable factors for risk reduction and provide caution measures. Materials and Methods: This cross-sectional observational study included 100 adult patients with T2DM on oral hypoglycemic drugs or insulin therapy. Based on glycemic control, type 2 diabetic patients were divided into four groups: Group 1 (poor glycemic control and hemoglobin A1C (HbA1c) >9%), Group 2 (fair glycemic control and HbA1c 8%–8.9%), Group 3 (good glycemic control and HbA1C 7–7.9%), and Group 4 (excellent glycemic control, HbA1C <7%). P < 0.05 was considered statistically significant. Results: Overall, significantly higher glycemic levels (fasting blood glucose, postprandial blood glucose, and HbA1c) and lipid derangements (cholesterol, low-density lipoprotein, and triglyceride) were found in patients with ED as compared to those without ED (P < 0.05). Baseline brachial artery diameter (D1) was into three groups, one group with D1 (≤3.6 mm) with mean flow-mediated dilatation (FMD) of 9.07%, Another group of D1 (3.61 mm to ≤4.30 mm) with mean FMD of 5.26%, and the third group with D1 (>4.41 mm) with mean FMD of 4.58%. There was a statistically significant association seen between baseline brachial artery diameter and FMD (P < 0.05). Multivariate linear regression showed that HbA1c and treatment of both Oral hypoglycemic agents (OHA) and insulin were the significant independent factors affecting the ED with OR of 7.566 (P = 0.0003) and 0.013 (P = 0.011), respectively. Conclusion: In diabetics, the risk of ED is increased with worsening levels of lipid profile and glycemia irrespective of the age and duration of the disease.

Nitric oxide-dependent micro- and macrovascular dysfunction occurs early in adolescents with type 1 diabetes.

Arterial stiffness and endothelial dysfunction are both reported in children with type 1 diabetes (DM1) and may predict future cardiovascular events. In health, nitric oxide (NO) relaxes arteries and increases microvascular perfusion. The relationships between NO-dependent macro- and microvascular functional responses and arterial stiffness have not been studied in adolescents with DM1. Here, we assessed macro- and microvascular function in DM1 adolescents and age-matched controls at baseline and during an oral glucose challenge (OGTT). DM1 adolescents (n = 16) and controls (n = 14) were studied before and during an OGTT. At baseline, we measured: 1) large artery stiffness using both aortic augmentation index (AI) and carotid-femoral pulse wave velocity (cfPWV); 2) brachial flow-mediated dilation (FMD) and forearm endothelial function using postischemic flow velocity (PIFV); and 3) forearm muscle microvascular blood volume (MBV) using contrast-enhanced ultrasound. Following OGTT, AI, cfPWV, and MBV were reassessed at 60 min and MBV again at 120 min. Within individual and between-group, comparisons were made by paired and unpaired t tests or repeated measures ANOVA. Baseline FMD was lower (P = 0.02) in DM1. PWV at 0 and 60 min did not differ between groups. Baseline AI did not differ between groups but declined with OGTT only in controls (P = 0.02) and was lower than DM1 at 60 min (P < 0.03). Baseline MBV was comparable in DM1 and control groups, but declined in DM1 at 120 min (P = 0.01) and was lower than the control group (P < 0.03). There was an inverse correlation between plasma glucose and MBV at 120 min (r = -0.523, P < 0.01). No differences were noted between groups for V̇O2max (mL/min/kg), body fat (%), or body mass index (BMI). NO-dependent macro- and microvascular function, including FMD and AI, and microvascular perfusion, respectively, are impaired early in the course of DM1, precede increases of arterial stiffness, and may provide an early indicator of vascular risk.NEW & NOTEWORTHY This is the first study to show that type 1 diabetes impairs multiple nitric oxide-dependent vascular functions.

Vascular health assessment with flow-mediated dilatation and retinal image analysis: a pilot study in an adult population from Cape Town.

Flow-mediated dilatation (FMD) and retinal vascular analysis (RVA) may assist in predicting cardiovascular disease (CVD) but are poorly characterised in South Africa. We recorded baseline FMD and retinal vascular widths in healthy participants, and investigated associations with cardiovascular risk factors. Endothelial function (measured with FMD), microvascular structure (evaluated via fundus image analysis) and major CVD risk factors were assessed in 66 participants from Cape Town. Median FMD% was 9.6%, with higher values in females. Mean retinal arteriolar and venular widths were ˜156 and ˜250 µm, respectively. FMD was not associated with CVD risk factors. Hypertension was associated with narrower retinal arterioles and venules. We report novel baseline FMD data in healthy South African adults from the Western Cape, and show that retinal microvascular calibres are associated with blood pressure. Our baseline FMD and RVA data could serve as a reference for future studies in South Africa.

Effect of melatonin supplementation on endothelial function in heart failure with reduced ejection fraction: A randomized, double‐blinded clinical trial

BackgroundThis study aimed to investigate the effect of melatonin supplementation on endothelial function in patients with heart failure with reduced ejection fraction (HFrEF).MethodsThis is an analysis of the MeHR trial, a randomized double‐blinded placebo‐controlled clinical trial with two parallel arms of 1:1. Oral 10 mg melatonin tablets or placebo was administered for 24 weeks. Deference in the percentage of flow‐mediated dilatation (FMD) after the intervention was the primary outcome.ResultsNinety‐two patients were included in the study (age: 62.7±10.3 years, 87.0% male, ejection fraction (EF): 28.6±8.1). After adjustment for baseline FMD and age, a statistically significant difference in post‐treatment FMD in favor of the melatonin group was seen (estimated marginal means [95%CI], melatonin: 7.84% [6.69–8.98], placebo: 5.98% [4.84–7.12], p = .027). There was no significant difference in the mean of post‐treatment systolic/diastolic blood pressure, serum total antioxidant capacity, and serum malondialdehyde (MDA) between groups. Subgroup analysis showed significant improvement in FMD and MDA in the melatonin group in nondiabetic patients, while no difference was seen between study groups in diabetic patients.ConclusionsMelatonin supplementation in HFrEF might improve endothelial function; however, this beneficial effect might not be seen in diabetic patients.

The Acute Effect of Magnesium Supplementation on Endothelial Function: A Randomized Cross-Over Pilot Study

Magnesium (Mg) deficiency might be a catalyst in the process of endothelial dysfunction, an early event in the pathogenesis of atherosclerosis. The aim of this study was to determine the acute effect of an oral Mg supplement as compared to control on endothelial function assessed by flow-mediated dilatation (FMD). Nineteen participants (39 years, body mass index (BMI) 22.9 kg/m2) completed this randomized cross-over study. Blood pressure (BP) and FMD were measured and blood samples were taken before participants drank 200 mL water, with or without an over the counter Mg supplement (450 mg and 300 mg for men and women). Measurements were repeated at 60 and 120 min. There was a statistically significant two-way interaction between treatment and time on serum Mg (p = 0.037). A difference of −0.085 mm in FMD was observed 60-min post drink in the control group, as compared to baseline FMD, and no difference was observed in the supplement group as compared to baseline. Despite the non-significant interaction between treatment and time on FMD, once adjusted for baseline, the difference seen in the control group and the lack of change in the supplement group at 60 min post-drink suggests that Mg might attenuate the reduction in FMD post-prandially.

Reduced Endothelial Function in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome-Results From Open-Label Cyclophosphamide Intervention Study.

Introduction: Patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) present with a range of symptoms including post-exertional malaise (PEM), orthostatic intolerance, and autonomic dysfunction. Dysfunction of the blood vessel endothelium could be an underlying biological mechanism, resulting in inability to fine-tune regulation of blood flow according to the metabolic demands of tissues. The objectives of the present study were to investigate endothelial function in ME/CFS patients compared to healthy individuals, and assess possible changes in endothelial function after intervention with IV cyclophosphamide.Methods: This substudy to the open-label phase II trial “Cyclophosphamide in ME/CFS” included 40 patients with mild-moderate to severe ME/CFS according to Canadian consensus criteria, aged 18–65 years. Endothelial function was measured by Flow-mediated dilation (FMD) and Post-occlusive reactive hyperemia (PORH) at baseline and repeated after 12 months. Endothelial function at baseline was compared with two cohorts of healthy controls (N = 66 and N = 30) from previous studies. Changes in endothelial function after 12 months were assessed and correlated with clinical response to cyclophosphamide. Biological markers for endothelial function were measured in serum at baseline and compared with healthy controls (N = 30).Results: Baseline FMD was significantly reduced in patients (median FMD 5.9%, range 0.5–13.1, n = 35) compared to healthy individuals (median FMD 7.7%, range 0.7–21, n = 66) (p = 0.005), as was PORH with patient score median 1,331 p.u. (range 343–4,334) vs. healthy individuals 1,886 p.u. (range 808–8,158) (p = 0.003). No significant associations were found between clinical response to cyclophosphamide intervention (reported in 55% of patients) and changes in FMD/PORH from baseline to 12 months. Serum levels of metabolites associated with endothelial dysfunction showed no significant differences between ME/CFS patients and healthy controls.Conclusions: Patients with ME/CFS had reduced endothelial function affecting both large and small vessels compared to healthy controls. Changes in endothelial function did not follow clinical responses during follow-up after cyclophosphamide IV intervention.