Endothelial Function In Adults Research Articles

Acute effects of MitoQ on vascular endothelial function are influenced by cardiorespiratory fitness and baseline FMD in middle-aged and older adults.

A key mechanism promoting vascular endothelial dysfunction is mitochondrial-derived reactive oxygen species (mtROS). Aerobic exercise preserves endothelial function in preclinical models by lowering mtROS. However, the effects of mtROS on endothelial function in exercising and non-exercising adults is limited. In a double-blind, randomized, placebo-controlled crossover study design 23 (10M/13 F, age 62.1 ± 11.5 years) middle-aged and older (MA/O, ≥45 years) adults were divided into two groups: exercisers (EX, n=11) and non-exercisers (NEX, n=12). All participants had endothelial function (brachial artery flow-mediated dilatation, FMDBA) measured before and ∼1h after mitoquinone mesylate (MitoQ) (single dose, 80mg) and placebo supplementation. A two-way repeated measures ANOVA was used to determine the effects of MitoQ and placebo on FMDBA. Pearson correlations assessed the association between the change in FMDBA with MitoQ and baseline FMDBA and cardiorespiratory fitness (CRF). Compared with placebo, MitoQ increased FMDBA in NEX by + 2.1% (MitoQ pre: 4.9 ± 0.4 vs. post: 7.0 ± 0.4 %, P=0.004, interaction) but not in EX (P=0.695, interaction). MitoQ also increased endothelial function in adults with a FMDBA <6% (P < 0.0001, interaction) but not >6% (P=0.855, interaction). Baseline FMDBA and CRF were correlated (r=0.44, P=0.037), whereas the change in FMDBA with MitoQ was inversely correlated with CRF (r=-0.66, P < 0.001) and baseline FMDBA (r=-0.73, P < 0.0001). The relationship between the change in FMDBA and baseline FMDBA remained correlated after adjusting for CRF (r=-0.55, P=0.007). These data demonstrate that MitoQ acutely improves FMDBA in NEX and EX adults who have a baseline FMDBA <6%. KEY POINTS: A key age-related change contributing to increased cardiovascular disease (CVD) risk is vascular endothelial dysfunction due to increased mitochondrial-derived reactive oxygen species (mtROS). Aerobic exercise preserves endothelial function via suppression of mtROS in preclinical models but the evidence in humans is limited. In the present study, a single dose of the mitochondria-targeted antioxidant, mitoquinone mesylate (MitoQ), increases endothelial function in non-exercisers with lower cardiorespiratory fitness (CRF) but not in exercisers with higher CRF. The acute effects of MitoQ on endothelial function in middle-aged and older adults (MA/O) are influenced by baseline endothelial function independent of CRF. These data provide initial evidence that the acute MitoQ-enhancing effects on endothelial function in MA/O adults are influenced, in part, via CRF and baseline endothelial function.

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

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

Reproducibility of a New Method to Assess Endothelial Function According to Peripheral Arterial Volume

Background: The assessment of endothelial function is crucial for understanding cardiovascular disease progression. Reliable, convenient non-invasive methods are necessary for evaluating endothelial function. Peripheral arterial volume (PAV), measured at the fingertip, is a novel approach for which limited reproducibility data are available. Hence, this study was aimed at evaluating PAV measurement reproducibility in a clinical setting. Method: A total of 152 consecutive patients (average age 55.8 ± 12.3 years, 83 men) with chest pain were included in the study. PAV tests were conducted on the same day. The amplitude ratio before and after application of pressure, along with the reference ratio, were recorded to calculate the PAV. Medical baseline data for these patients were gathered from the hospital’s records. Result: On test days, the PAV results from repeated measurements were 1.15 ± 0.33 and 1.15 ± 0.31 (P = 0.99), indicating no significant difference between measurements in all participants. The mean difference was 0.00 ± 0.32, thus indicating no systematic errors, and the intraclass correlation coefficient was 0.66. Furthermore, age, sex, and BMI did not influence PAV reproducibility. Conclusion: PAV measurement is feasible and exhibited excellent reproducibility among all enrolled patients. As a novel fingertip measurement, PAV has promise as a convenient and accurate method for assessing endothelial function in adults.

A nutraceutical with Citrus bergamia and Cynara cardunculus improves endothelial function in adults with non-alcoholic fatty liver disease

ObjectivePolyphenol intake may prevent hepatic steatosis and cardiovascular disease by potentially improving endothelial function. The purposes of this study are to investigate the association between fatty liver disease and endothelial dysfunction and to test the effects of a nutraceutical containing extracts made from Citrus bergamia and Cynara cardunculus on peripheral vascular endothelial function in adults with liver steatosis. MethodsWe analyzed data from 32 individuals with hepatic steatosis and endothelial dysfunction (reactive hyperemia index ≤ 1.67). Sixteen subjects took 1 capsule/d (300 mg/d) containing Cynara cardunculus extract and bergamot polyphenol fraction, while the other 16 subjects matched for age, sex, and body mass index took 1 capsule/d of placebo (maltodextrin) for 12 wk. All anthropometric parameters were assessed at baseline and after 12 wk as were lipids, glucose, and reactive hyperemia index using an EndoPAT 2000. ResultsThe mean age was 52 ± 9 y. The mean reactive hyperemia index was 1.15 ± 0.4. After 12 wk, we found a greater increase in reactive hyperemia index in the participants taking the nutraceutical rather than placebo (0.58 ± 0.5 versus 0.13 ± 0.5; P = 0.02, respectively). The stepwise multivariable analysis confirmed a positive association between reactive hyperemia index change and the nutraceutical treatment (B = 0.38; P = 0.025) and negative association with reactive hyperemia index values at baseline (B = –0.81; P < 0.001). No association was found between the reduction in the amount of intrahepatic fat and the improvement of endothelial function (B = 0.002; P = 0.56). ConclusionsA nutraceutical containing bergamot and artichoke extracts improves peripheral vascular endothelial function in adults with hepatic steatosis and early phase of atherosclerosis.

Exploring mechanisms of blood pressure regulation in response to device-guided and non-device-guided slow breathing: A mini review.

Hypertension is a widespread disease that, if persistent, increases the risks of coronary heart disease mortality and morbidity. Slow breathing is a recommended blood pressure-lowering strategy though the mechanisms mediating its effects are unknown. This review aims to evaluate autonomic and vascular function as potential mediators driving BP adaptive responses with slow breathing. We searched EBSCO host, Web of Science, Cochrane Central Register of Controlled Trials, and PubMed using key words for optimized search results. Nineteen studies were included in this review (11 device-guided; 8 non-device-guided breathing). Though some studies showed increased vagally mediated components of heart rate variability during slow breathing, results from acute and long-term studies were incongruent. Increases in baroreflex sensitivity (BRS) following a single device-guided slow breathing bout were noted in normotensive and hypertensive adults. Long-term (4weeks to 3months) effects of slow breathing on BRS were absent. Device-guided breathing resulted in immediate reductions in muscle sympathetic nerve activity (MSNA) in normo- and hyper-tensive adults though results from long-term studies yielded inconsistent findings. Non-device-guided slow breathing posed acute and chronic effects on vascular function with reductions in arterial stiffness in adults with type I diabetes and increases in microvascular endothelial function in adults with irritable bowel syndrome. Non-device guided breathing also reduced pro-inflammatory cytokines in healthy and hypertensive adults in acute and chronic studies. No adverse effects or non-adherence to treatment were noted in these trials. Device-guided slow breathing is a feasible and effective modality in improving BRS, HRV, and arterial stiffness though its long-term effects are obscure. Though less evidence exists supporting the efficacy of non-device-guided slow breathing, acute and chronic studies demonstrate improvements in vascular function and inflammatory cytokines. More studies are needed to further explore the long-term effects of slow breathing in general and non-device-guided breathing in particular.

Pharmacological effects of statins in adult patients with type 2 diabetes mellitus: A protocol for systematic review and meta-analysis.

Due to contradicting findings on impact of statins on endothelial function in type 2 diabetes mellitus especially across the randomized controlled trials (RCTs). With this systematic review, we aim to evaluate whether the use of statins improves endothelial function in adults with type 2 diabetes. We will further highlight if these biomarkers are ideal therapeutic targets for risk for atherosclerosis and cardiovascular disease. This protocol was carried out according to the preferred reporting items for systematic review and meta-analysis protocols-2015 guideline. The online databases, such as MEDLINE, Scopus, and Web of Sciences, will be targeted using the medical subject heading terms (MeSH) and text words. The review will include clinical studies on the effect of statins on markers of endothelial function in type 2 diabetes. The Cochrane risk of bias guideline will be used to assess the quality and risk of bias. We are planning to use the grading of recommendation assessment, development, and evaluation approach to evaluate the strength and quality of evidence. This study will not involve human samples and patient data; hence ethics approval will not be required. The findings will be presented in journal clubs and conferences and published in peer-reviewed journals.

Exercise capacity, cardiac and endothelial function in adults with repaired tetralogy of Fallot

BackgroundExercise capacity and endothelial function are impaired in adults with repaired tetralogy of Fallot (ToF). This may be related to pathophysiological determinants, such as cardiac and endothelial impairment, or to a more sedentary lifestyle. Therefore, we sought to assess if cardiac and endothelial function are associated with exercise capacity in adults with repaired ToF. MethodsIn a case-control study, we compared adults with repaired ToF and controls in terms of exercise workload, peak oxygen consumption (VO2peak) and flow-mediated dilation (FMD). Additionally, we determined associations of natriuretic peptide levels, echocardiographic parameters of size, function and systolic pressure with exercise capacity. ResultsA total of 26 patients (mean age 38 ​± ​10 years, 46% males) and 10 controls were included. Patients with repaired ToF had reduced VO2peak (25.0 vs. 36.3 ​ml/kg/min, p ​< ​0.001) and FMD (7.6 vs. 10.8%, p ​= ​0.007) compared to controls. Exercise workload was moderately associated with FMD (r ​= ​0.428, p ​= ​0.029) and right ventricular parameters, while VO2peak was moderately associated with natriuretic peptide levels (r ​= ​−0.523, p ​= ​0.006). ConclusionsAdults with repaired ToF have impaired exercise capacity and endothelial function as compared to healthy controls. Natriuretic peptide levels and FMD are moderately associated with exercise capacity in adults with repaired ToF.

Arsenic exposure from drinking water and endothelial dysfunction in Bangladeshi adolescents

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide, with ∼80% of CVD-related deaths occurring in low- and middle-income countries. Growing evidence suggests that chronic arsenic exposure may contribute to CVD through its effect on endothelial function in adults. However, few studies have examined the influence of arsenic exposure on cardiovascular health in children and adolescents. To examine arsenic's relation to preclinical markers of endothelial dysfunction, we enrolled 200 adolescent children (ages 15–19 years; median 17) of adult participants in the Health Effects of Arsenic Longitudinal Study (HEALS), in Araihazar, Bangladesh. Participants' arsenic exposure was determined by recall of lifetime well usage for drinking water. As part of HEALS, wells were color-coded to indicate arsenic level (<10 μg/L, 10–50 μg/L, >50 μg/L). Endothelial function was measured by recording fingertip arterial pulsatile volume change and reactive hyperemia index (RHI) score, an independent CVD risk factor, was calculated from these measurements. In linear regression models adjusted for participant's sex, age, education, maternal education, land ownership and body weight, individuals who reported always drinking water from wells with >50 μg/L arsenic had a 11.75% lower level of RHI (95% CI: −21.26, −1.09, p = 0.03), as compared to participants who drank exclusively from wells with ≤50 μg/L arsenic. Sex-stratified analyses suggest that these associations were stronger in female participants. As compared to individuals who drank exclusively from wells with ≤50 μg/L arsenic, the use of wells with >50 μg/L arsenic was associated with 14.36% lower RHI (95% CI: −25.69, −1.29, p = 0.03) in females, as compared to 5.35% lower RHI (95% CI: −22.28, 15.37, p = 0.58) in males for the same comparison. Our results suggest that chronic arsenic exposure may be related to endothelial dysfunction in adolescents, especially among females. Further work is needed to confirm these findings and examine whether these changes may increase risk of later adverse cardiovascular health events.

Dietary Strawberries Improve Biomarkers of Antioxidant Status and Endothelial Function in Adults with Cardiometabolic Risks in a Randomized Controlled Crossover Trial.

Strawberries, a popularly consumed berry fruit, are rich in bioactive compounds with antioxidant effects. In this study, we examined the effects of two dietary achievable doses of strawberries on the antioxidant status and biomarkers of endothelial function in adults with features of metabolic syndrome and a confirmed low baseline of fruit and vegetable intake. In a 14-week randomized controlled crossover study, participants were assigned to one of three groups for four weeks separated by a one-week washout period: control powder, one serving (low dose: 13 g strawberry powder/day), or 2.5 servings (high dose: 32 g strawberry powder/day). Blood samples and health data were collected at baseline and at the end of each four-week phase of intervention. Thirty-three participants completed all three phases of the trial. Significant increases were observed in serum antioxidant capacity and superoxide dismutase activity as well as decreases in lipid peroxidation after both low and high dose strawberry phases when compared with the control phase. Significant decreases were also observed in soluble vascular cell adhesion molecule-1 and tumor necrosis factor-α with the high dose strawberry phase. These data confirm that consuming strawberries for four weeks significantly improves antioxidant status, endothelial function, and inflammation in adults with cardiometabolic risks.

Hydrogen sulfide-dependent microvascular vasodilation is improved following chronic sulfhydryl-donating antihypertensive pharmacotherapy in adults with hypertension.

Hypertension is characterized by systemic microvascular endothelial dysfunction, in part due to a functional absence of hydrogen sulfide (H2S)-mediated endothelium-dependent dilation. Treatment with a sulfhydryl-donating ACE inhibitor (SH-ACE inhibitor) improves endothelial function in preclinical models of hypertension. To date, no studies have directly assessed the effects of SH-ACE-inhibitor treatment on H2S-dependent vasodilation in humans with hypertension. We hypothesized that SH-ACE-inhibitor treatment would improve H2S-mediated endothelium-dependent vasodilation. Ten adults with hypertension [1 woman and 9 men; 56 ± 9 yr; systolic blood pressure (SBP): 141 ± 8.5 mmHg; diastolic blood pressure (DBP): 90.3 ± 6 mmHg] were treated (16 wk) with the SH-ACE-inhibitor captopril. Red blood cell flux (laser-Doppler flowmetry) was measured continuously during graded intradermal microdialysis perfusion of the endothelium-dependent agonist acetylcholine (ACh; 10-10 to 10-1 M) alone (control) and in combination with an inhibitor of enzymatic H2S production [10-3 M aminooxyacetate (AOAA)] preintervention and postintervention. Cutaneous vascular conductance (CVC; flux/mmHg) was calculated and normalized to the site-specific maximal CVC (0.028 M sodium nitroprusside and local heat to 43°C). Area under the curve was calculated using the trapezoid method. The 16-wk SH-ACE-inhibitor treatment resulted in a reduction of blood pressure (systolic BP: 129 ± 10 mmHg; diastolic BP: 81 ± 9 mmHg, both P < 0.05). Preintervention, inhibition of H2S production had no effect on ACh-induced vasodilation (316 ± 40 control vs. 322 ± 35 AU AOAA; P = 0.82). Captopril treatment improved ACh-induced vasodilation (316 ± 40 pre vs. 399 ± 55 AU post; P = 0.04) and increased the H2S-dependent component of ACh-induced vasodilation (pre: -6.6 ± 65.1 vs. post: 90.2 ± 148.3 AU, P = 0.04). These data suggest that SH-ACE-inhibitor antihypertensive treatment improves cutaneous microvascular endothelium-dependent vasodilation in adults with hypertension, in part via H2S-dependent mechanisms.NEW & NOTEWORTHY This is the first study to prospectively assess the effects of sulfhydryl antihypertensive treatment on microvascular endothelial function in adults with hypertension. Our data suggest that 16 wk of SH-ACE-inhibitor antihypertensive treatment improves cutaneous microvascular endothelium-dependent vasodilation in middle-aged adults with hypertension, in part via H2S-dependent mechanisms.

Low-to-Moderate-Intensity Resistance Exercise Is More Effective than High-Intensity at Improving Endothelial Function in Adults: A Systematic Review and Meta-Analysis.

Aerobic exercise has been confirmed to improve endothelial function (EF). However, the effect of resistance exercise (RE) on EF remains controversial. We conducted this systematic review and meta-analysis on randomized controlled trials (RCTs) to determine the effect of RE and its intensities on EF. We searched Web of Science, PubMed/MEDLINE, Scopus, and Wiley Online Library, and included 15 articles (17 trials) for the synthesis. Overall, RE intervention significantly improved flow-mediated dilatation (FMD) in brachial artery (SMD = 0.76; 95% CI: 0.47, 1.05; p < 0.00001), which represents improved EF. Meta-regression showed that the RE intensity was correlated with changes in FMD (Coef. = −0.274, T = −2.18, p = 0.045). We found both intensities of RE improved FMD, but the effect size for the low- to moderate-intensity (30–70%1RM) was bigger (SMD = 1.02; 95% CI: 0.60, 1.43; p < 0.0001) than for the high-intensity (≥70%1RM; SMD = 0.48; 95% CI: 0.21, 0.74; p = 0.005). We further noticed that RE had a beneficial effect (SMD = 0.61; 95% CI: 0.13, 1.09; p = 0.01) on the brachial artery baseline diameter at rest (BADrest), and the age variable was correlated with the changes in BADrest after RE (Coef. = −0.032, T = −2.33, p = 0.038). Young individuals (<40 years) presented with a bigger effect size for BADrest (SMD = 1.23; 95% CI: 0.30, 2.15; p = 0.009), while middle-aged to elderly (≥40 years) were not responsive to RE (SMD = 0.07; 95% CI: −0.28, 0.42; p = 0.70). Based on our findings, we conclude that RE intervention can improve the EF, and low- to moderate-intensity is more effective than high-intensity.

Strawberry Consumption, Cardiometabolic Risk Factors, and Vascular Function: A Randomized Controlled Trial in Adults with Moderate Hypercholesterolemia.

Certain fruits, such as strawberries, may impart cardiometabolic benefits due to their phytochemical content. Study aims were to assess the effects of strawberry intake on cardiometabolic risk factors and vascular endothelial function in adults with moderate hypercholesterolemia. This study was a randomized, controlled, double-blinded, 2-arm, 2-period (4-wk/period) crossover trial. Adults (n=34; male/female 1:1; mean±SEM age, 53±1y; BMI, 31±1kg/m2; LDL cholesterol, 133±3mg/dL)were randomly allocated to 1 of 2 study sequences in a 1:1 ratio. Participants drank study beverages twice daily containing freeze-dried strawberry powder (2× 25 g)orenergy-, volume-matched control powder for 4 wk separated by a 4-wk washout. The primary outcome variable was the difference in fasting LDL cholesterol after 4-wk interventions. Secondary outcomes were metabolic markers, inflammation, quantitative (poly)phenolic metabolomics, flow-mediated dilation (FMD), and blood pressure (BP), with the latter (FMD, BP) also assessed acutely at 1h and 2h after a 50-gbolus strawberry or control beverage. Mixed-model analysis of repeated measures via PROC MIXED, PC-SAS was performed on primary and secondary outcome variables. LDL cholesterol did not differ after the 4-wk interventions (P>0.05), nor did fasting total cholesterol, triglycerides, glucose, insulin, high-sensitivity C-reactive protein, FMD, or BP (all P >0.05). Significant intervention-by-hour interaction for FMD (P=0.03) and BP (P=0.05) revealed increased FMD at 1h after strawberry compared with control by 1.5±0.38%(P=0.0008) and attenuated systolic BP at 2h by 3.1±0.99mmHg(P=0.02). Select phenolic metabolites increased significantly (P<0.05) in blood following strawberry consumption while others decreased, including 3-(4-methoxyphenyl)propanoic acid-3-O-glucuronide, which was significantly correlated with increased FMD (P<0.05). Strawberries may improve vascular health, independent of other metabolic changes. The effect may be related to changes in microbial-derived phenolic metabolites after strawberry consumption influencing endothelial function. Data support inclusion of strawberries in a heart-healthy diet in adults with moderate hypercholesterolemia.This trial was registered at clinicaltrials.gov as NCT02612090.

Post-prandial effects of high-polyphenolic extra virgin olive oil on endothelial function in adults at risk for type 2 diabetes: A randomized controlled crossover trial

BackgroundEffects of olive oil on cardiovascular risk have been controversial. We compared the effects of high-polyphenolic extra virgin olive oil (EVOO) and refined olive oil without polyphenols on endothelial function (EF) in adults at risk for Type 2 diabetes mellitus (T2DM). MethodsRandomized, controlled, double-blind, crossover trial of 20 adults (mean age 56.1 years; 10 women, 10 men) at risk for T2DM (i.e., as defined by either prediabetes or metabolic syndrome) assigned to one of two possible sequence permutations of two different single dose treatments (50 mL of high-polyphenolic EVOO or 50 mL of refined olive oil without polyphenols), with 1-week washout. Participants received their olive oils in a smoothie consisting of ½ cup frozen blueberries and 1 cup (8 oz) low-fat vanilla yogurt blended together. Primary outcome measure was EF measured as flow-mediated dilatation. Participants were evaluated before and 2 h after ingestion of their assigned olive oil treatment. ResultsEVOO acutely improved EF as compared to refined olive oil (1.2 ± 6.5% versus −3.6 ± 3.8%; p = 0.0086). No significant effects on systolic or diastolic blood pressure were observed. ConclusionsHigh-polyphenolic EVOO acutely enhanced EF in the study cohort, whereas refined olive oil did not. Blood pressure effects were not observed. Reports on the vascular effects of olive oil ingestion should specify the characteristics of the oil. Clinical trial registration numberNCT04025281

Vascular function in adults with cyanotic congenital heart disease.

BackgroundPatients with cyanotic congenital heart disease (CCHD) may have a low burden of atherosclerosis. Endothelial dysfunction is an early stage of atherosclerosis and endothelial function is previously studied in smaller CCHD groups with different techniques and variable results. We aimed to examine endothelial function and carotid atherosclerosis in a larger group of CCHD patients.MethodsThis multicentre study assessed endothelial function in adults with CCHD and controls by measuring the dilatory response of the brachial artery to post-ischemic hyperaemia (endothelium-dependent flow-mediated-vasodilatation (FMD)), and to nitroglycerin (endothelium-independent nitroglycerin-induced dilatation (NID)). Flow was measured at baseline and after ischaemia (reactive hyperaemia). Carotid-intima-media-thickness (CIMT), prevalence of carotid plaque and plaque thickness (cPT-max) were evaluated ultrasonographically. Lipoproteins, inflammatory and vascular markers, including sphingosine-1-phosphate (S1P) were measured.ResultsForty-five patients with CCHD (median age 50 years) and 45 matched controls (median age 52 years) were included. The patients presented with lower reactive hyperaemia (409 ± 114% vs. 611 ± 248%, p < 0.0001), however preserved FMD response compared to controls (106.5 ± 8.3% vs. 106.4 ± 6.1%, p = 0.95). In contrast, NID was lower in the patients (110.5 ± 6.1% vs. 115.1 ± 7.4%, p = 0.053). There was no difference in CIMT, carotid plaque or cPT-max. The patients presented with lower high-density-lipoprotein cholesterol, and higher level of inflammatory markers and S1P.ConclusionAdults with CCHD had preserved FMD in the brachial artery, but impaired NID response and lower reactive hyperaemia than controls. The preserved FMD and the comparable prevalence of carotid atherosclerosis indicate that CCHD patients have the same risk of atherosclerosis as controls.

Post-Prandial Effects of High-polyphenolic Extra Virgin Olive Oil on Endothelial Function in Adults at Risk for Type 2 Diabetes: A Randomized Controlled Crossover Trial

Abstract Objectives The effects of olive oil on cardiovascular risk have been controversial. We compared the effects of high-polyphenolic extra virgin olive oil (EVOO) and refined olive oil without polyphenols on endothelial function (EF) in adults at risk for Type 2 diabetes. Methods Randomized, controlled, double-blind, crossover trial of 20 adults (mean age 56.1 years; 10 women, 10 men) at risk for Type 2 diabetes (i.e., as defined by either prediabetes or metabolic syndrome) assigned to one of two possible sequence permutations of two different single dose treatments (50 mL of high-polyphenolic EVOO or 50 mL of refined olive oil without polyphenols), with 1-week washout. Participants received their olive oils in a smoothie consisting of ½ cup frozen blueberries and 1 cup (8oz) low fat yogurt (Crowley low-fat vanilla) blended together and served in a 20 oz. plastic cup. Our primary outcome measure was EF measured as flow-mediated dilatation. Blood pressure was a secondary outcome measure. Participants were evaluated before and 2 hours after ingestion of their assigned olive oil treatment. Results EVOO acutely improved endothelial as compared to refined olive oil (1.2 ± 6.5% versus −3.6 ± 3.8%; P = 0.0086). No significant effects on systolic or diastolic blood pressure (i.e., −0.9 ± 7.1 mmHg versus −0.6 ± 9.8 mmHg; P = 0.9122 and −1.6 ± 5.0 mmHg versus −1.1 ± 7.6 mmHg; P = 0.8061 respectively) were observed. Conclusions High-polyphenolic EVOO acutely enhanced endothelial function in the study cohort, whereas refined olive oil did not. Blood pressure effects were not observed. The vascular effects of olive oil ingestion should specify the characteristics of the oil. Funding Sources Cobram Estate Extra Virgin Olive Oil.

Mediterranean Diet Increases Endothelial Function in Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background:The endothelium plays a key role in the maintenance of vascular health and represents a potential physiological target for dietary and other lifestyle interventions designed to reduce the risk of cardiovascular diseases (CVD) including stroke or coronary heart disease. Objective:To conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) investigating the effects of the Mediterranean dietary pattern (MedDiet) on endothelial function. Methods:Medline, Embase, and Scopus databases were searched from inception until January 2019 for studies that met the following criteria:1) RCTs including adult participants,2) interventions promoting the MedDiet,3) inclusion of a control group, and4) measurements of endothelial function. A random-effects meta-analysis was conducted. Metaregression and subgroup analyses were performed to identify whether effects were modified by health status (i.e., healthy participants versus participants with existing comorbidities), type of intervention (i.e., MedDiet alone or with a cointervention), study duration, study design (i.e., parallel or crossover), BMI, and age of participants. Results:Fourteen articles reporting data for 1930 participants were included in the meta-analysis. Study duration ranged from 4 wk to 2.3 y. We observed a beneficial effect of the MedDiet on endothelial function [standardized mean difference (SMD): 0.35; 95% CI: 0.17, 0.53;P <0.001;I2 = 73.68%]. MedDiet interventions improved flow-mediated dilation (FMD)–the reference method for noninvasive, clinical measurement of endothelial function–by 1.66% (absolute change; 95% CI: 1.15, 2.17;P <0.001;I2 = 0%). Effects of the MedDiet on endothelial function were not modified by health status, type of intervention, study duration, study design, BMI, or age of participants (P >0.05). ConclusionsMedDiet interventions improve endothelial function in adults, suggesting that the protective effects of the MedDiet are evident at early stages of the atherosclerotic process with important implications for the early prevention of CVD. This study has the PROSPERO registration number: CRD42018106188.

Almond snack consumption improves endothelial function in adults with moderate risk of cardiovascular disease: a randomised, controlled, parallel trial

AbstractEndothelial dysfunction is a predictor for cardiovascular disease risk and is a key feature of atherosclerosis. Poor diet quality, including consumption of saturated fat-rich, high-refined carbohydrate snack foods, may have adverse effects on endothelial function. Thus, snack foods, which contribute an average of 20% of energy intake in the UK adult population, present an easily identifiable target to improve vascular health. Almonds are nutrient-dense foods that are rich in unsaturated fats, fibre, minerals and non-nutrient bioactives (NNB), and may have health benefits by displacing snacks high in refined carbohydrates, enriching the diet with micronutrients and NNB, and/or low lipid bioaccessibility. Human clinical trials have demonstrated LDL cholesterol-lowering effects of daily almond consumption, yet the effects on endothelial function are unclear. This study aimed to investigate whether replacing habitual snacks (20% estimated daily energy requirements) with almonds had any impact on endothelium-dependent vasodilation, measured by flow-mediated dilatation (FMD) using ultrasound imaging of the brachial artery following reactive hyperaemia. A randomised, controlled, parallel trial in adult regular snack consumers aged 30–70 y at moderate risk of cardiovascular disease was conducted, including a 2-week run-in period with control snacks and a 6-week intervention period. Control sweet and savoury mini muffin snacks were developed to replicate the average UK snack nutrient profile, which was calculated from snack foods identified in the UK National Diet and Nutrition Survey (NDNS) database (55% energy from carbohydrate, 36% total fat (14% saturated fat), and 10% protein). One hundred and nine volunteers (77 females and 32 males; mean age 56 y) were enrolled in the study and 107 were randomised to isocaloric treatments, 1) control muffins, or 2) dry roasted whole almonds; 105 participants completed the study. Almonds significantly increased FMD relative to control (mean difference 3.6%, 95% CI 1.7, 5.5; P &lt; 0.001), indicating improved endothelial function, and LDL-cholesterol (mean difference -0.25 mmol/L, 95% CI -0.47, -0.03; P = 0.030) significantly decreased adjusted with sex, age and baseline BMI and baseline dependent outcome values. Snacking on whole almonds as a replacement for snacks high in refined starch and sugar, and low in fibre and unsaturated fatty acids, improves endothelial function. The results of this study provide further evidence for the importance of nuts in dietary strategies to reduce risk of cardiovascular disease.

Post-prandial Effects of Extra Virgin Olive Oil on Endothelial Function in Adults at Risk for Type 2 Diabetes: A Randomized Crossover Controlled Trial

Post-prandial Effects of Extra Virgin Olive Oil on Endothelial Function in Adults at Risk for Type 2 Diabetes: A Randomized Crossover Controlled Trial

High‐Intensity Interval Training and Moderate‐Intensity Continuous Training Improve Endothelial Function Similarly in Adults with Type 2 Diabetes

Endothelial function is a predictor of cardiovascular disease, the leading cause of death in adults with type 2 diabetes. Aerobic exercise training may preserve or improve endothelial function; however, the optimal exercise prescription remains uncertain. Recently, there has been increasing interest in high‐intensity interval training (HIIT) vs. moderate‐intensity continuous training (MICT). These protocols are most commonly performed on the treadmill which may limit implementation in patients who have lower limb limitations or balance issues. We sought to compare the effect of non‐weight‐bearing all‐extremity HIIT vs. MICT on endothelial function in adults with type 2 diabetes. Forty‐nine sedentary men and postmenopausal women with type 2 diabetes aged 46 to 78 yrs (mean±SE: 63±1 yrs), free of cardiovascular disease, were randomized to HIIT (n=18), MICT (n=16), or non‐exercise control (CONT; n=15). HIIT (4×4‐min intervals at 90% of peak heart rate (HRpeak) interspersed by 3 min recovery bouts at 70% HRpeak) and isocaloric MICT (32 min at 70% of HRpeak) were performed on an Airdyne® all‐extremity ergometer 4 days/week under supervision. Including warm‐up and cool‐down, the total exercise duration per session was 40 min for HIIT and 47 min for MICT. Endothelial function in response to reactive hyperemia was assessed non‐invasively by brachial artery flow‐mediated dilation (FMD) via ultrasonography. Following the 8‐week intervention, FMD increased similarly in HIIT (pre‐ vs. post‐intervention: 3.17±0.62 vs. 4.03±0.71%, P=0.01) and MICT (3.54±0.63 vs. 4.39±0.61%; P=0.02 and P&gt;0.99 for HIIT vs. MICT) while it did not change in CONT (4.02±0.46 vs. 3.74±0.51%, P=0.4). The improvement in FMD was not confounded by changes in brachial baseline diameter, hyperemic shear rate, or systolic and diastolic blood pressure (P≥0.3). In conclusion, all‐extremity HIIT and MICT similarly improve endothelial function in adults with type 2 diabetes which suggests that all‐extremity MICT is an effective alternative for those who are unable or unwilling to engage in all‐extremity HIIT.Support or Funding InformationThis work was supported by National Institute of Aging grant AG050203 to DDC.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Dairy milk, regardless of fat content, protects against postprandial hyperglycemia-mediated impairments in vascular endothelial function in adults with prediabetes by limiting oxidative stress responses that reduce nitric oxide bioavailability

Postprandial hyperglycemia (PPH) transiently impairs vascular endothelial function (VEF) in an oxidative-stress-dependent manner by decreasing nitric oxide (NO•) bioavailability. Dairy milk, regardless of fat content, attenuates PPH, but whether this improves VEF by limiting oxidative stress responses that otherwise decrease NO• bioavailability is not known. We hypothesized that nonfat and full-fat dairy milk would similarly improve VEF by attenuating PPH-induced oxidative stress that otherwise decreases NO• biosynthesis and bioavailability. A randomized, crossover trial was conducted in adults with prediabetes (n=22) who ingested glucose (75 g) dissolved in 473 ml of water (GLU), or glucose with an equal volume of nonfat dairy milk (NFM) or full-fat dairy milk (FFM). Prior to and at 30-min intervals for 180 min postprandially, we assessed brachial artery flow-mediated dilation (FMD) and measured circulating biomarkers of glycemic control, oxidative stress and NO• homeostasis. AUC0–180 min for FMD and NO• metabolites was lowest in GLU but relatively greater in NFM and FFM. Compared with GLU, AUCs for glucose, malondialdehyde, F2-isoprostanes and endothelin-1 were similarly lower in dairy trials. Milk-mediated vasoprotection was accompanied by greater levels of plasma arginine and lower levels of asymmetric dimethylarginine and symmetric dimethylarginine. Postprandial insulin, lipids and tetrahydrobiopterin redox status did not differ among trials. Thus, dairy milk, regardless of its fat content, attenuates PPH-mediated impairments in VEF by limiting oxidative stress. This improves NO• bioavailability to the vascular endothelium by increasing arginine availability and limiting competitive inhibition on NO• biosynthesis by asymmetric dimethylarginine.