Flow-mediated Dilation Response Research Articles

Influence of cardiorespiratory fitness and body composition on resting and post-exercise indices of vascular health in young adults

Poor cardiorespiratory fitness may mediate vascular impairments at rest and following an acute bout of exercise in young healthy individuals. This study aimed to compare flow mediated dilation (FMD) and vascular augmentation index (AIx75) between young adults with low, moderate, and high levels of cardiorespiratory fitness before and after an acute bout of aerobic exercise. Forty-three participants (22 men; 21 women) between 18 and 29 years of age completed the study. Participants were classified into low, moderate, and high health-related cardiorespiratory fitness groups according to age- and sex-based relative maximal oxygen consumption (V˙O2 max) percentile rankings. FMD was performed using Doppler ultrasound and AIx75 was performed using pulse wave analysis at baseline and 60-min after a 30-min bout of treadmill running at 70% V˙O2 max. A significant interaction (p ​= ​0.047; ηp2 ​= ​0.142) was observed, with the moderate fitness group exhibiting a higher FMD post-exercise compared with baseline ([6.7% ​± ​3.1%] vs. [8.5% ​± ​2.8%], p ​= ​0.028; d ​= ​0.598). We found a significant main effect of group for AIx75 (p ​= ​0.023; ηp2 ​= ​0.168), with the high fitness group exhibiting lower AIx75 compared to low fitness group ([−10% ​± ​10%] vs. [2% ​± ​10%], respectively, p ​= ​0.019; g ​= ​1.07). This was eliminated after covarying for body fat percentage (p ​= ​0.489). Our findings suggest that resting FMD and AIx75 responses are not significantly influenced by cardiorespiratory fitness, but FMD recovery responses to exercise may be enhanced in individuals with moderate cardiorespiratory fitness levels.

Endothelial Dysfunction and Cardiometabolic Risk Factors in Mexican American Adults: The Cameron County Hispanic Cohort

Endothelial dysfunction assessed by impaired brachial flow-mediated dilation (FMD) predicts incident cardiovascular disease (CVD). We have previously shown that clustering of diabetes mellitus, obesity, and metabolic syndrome in young Hispanic patients was associated with subclinical atherosclerosis. This study aimed to assess determinants of impaired FMD response (%FMD), an earlier marker of atherosclerosis, in a population-based sample of asymptomatic Mexican Americans. Cardiometabolic biomarkers and FMD were obtained from 960 Cameron County Hispanic Cohort participants. Gender-specific median values of %FMD were used to categorize participants into those with %FMD below or above the median. The sample was further stratified into those younger and older than 55years. Survey-weighted logistic regression analyses were conducted to evaluate the effects of cardiometabolic biomarkers on the %FMD groups. The low %FMD group was significantly older, had higher visceral adipose tissue, systolic blood pressure, or plasma glucose, and had metabolic syndrome compared with those in the high %FMD group. Multivariable-adjusted age-stratified logistic regression analyses showed that in older participants, male gender (odds ratio [OR]=2.4 [1.4 to 4.2]) and having hypertension (OR=2.3 [1.3 to 4.3]) or prediabetes mellitus (OR=3.4 [1.5 to 7.5]) remained significantly associated with odds of low %FMD. In younger participants, high low-density lipoprotein (OR=2.8 [1.6 to 4.9]) or having the metabolic syndrome (OR=1.9 [1.1 to 3.6]) were significantly associated with odds of low %FMD. In conclusion, we found age-dependent associations between cardiometabolic biomarkers and an FMD response below the gender-specific median in a sample composed of Mexican Americans without previous CVD. Targeting specific risk factors by age may mitigate progression to incident CVD in this high-risk racial disparity group.

Noninvasive Brachial Artery Mechanics and Endothelial Function

I t has been recognized that endothelial dysfunction is an early indication of Arterial disease. Endothelial function can be noninvasively evaluated by Inducing a temporary increase in blood flow and then observing the degree of vasodilation response or flow-mediated dilation. Impaired flow mediated vasodilation is then an indication of impaired endothelium. Vascular ultrasound Imaging has been the typical approach to access vasodilation by flow-mediated dilation most often at the brachial artery. Together with other measures of cardiovascular risk, the flow-mediated dilation response provides a very early noninvasive screen for cardiovascular disease. The skill and equipment required for brachial artery ultrasound imaging have limited the use of flow-mediated dilation as a routine medical test. Moreover, it has been recognized that other vascular parameters such as vessel size and blood pressure may influence the test itself. We have introduced a potential solution to the routine measurement of flow-mediated dilation by Analyzing the response of a simple occlusive arm cuff to obtain the Brachial Artery diameter in a noninvasive way. The analysis for occlusive cuff Plethysmography was provided here in a calibrated manner. This approach is an alternative to ultrasound flow-mediated dilation testing. It requires no special operator skills and may be automated for precision. Two experimental evaluations of the proposed cuff method are provided. First, The cuff- based brachial diameters were compared to Ultrasound obtained diameters. Second, as a sensitivity test, the cuff-based dilation test was used to measure the dilation response of several subjects to blood sugar loading. For further evaluation, the cuff-based measurements were applied to a mechanical model of the brachial artery to reveal a standard error of estimate less than 5%. The results show that the cuff-based diameters compare well to those obtained via ultrasound imaging. Moreover, the cuff-based dilation testing showed the expected reduction in endothelial function response due to a blood sugar load. Additionally, cuff-based flow-mediated dilation testing provides measurements as a function of the subject blood pressure, which Ultrasound generally cannot.

Chronic anemia is associated with systemic endothelial dysfunction.

In acute myocardial infarction and heart failure, anemia is associated with adverse clinical outcomes. Endothelial dysfunction (ED) is characterized by attenuated nitric oxide (NO)-mediated relaxation responses which is poorly studied in chronic anemia (CA). We hypothesized that CA is associated with ED due to increased oxidative stress in the endothelium. CA was induced by repeated blood withdrawal in male C57BL/6J mice. Flow-Mediated Dilation (FMD) responses were assessed in CA mice using ultrasound-guided femoral transient ischemia model. Tissue organ bath was used to assess vascular responsiveness of aortic rings from CA mice, and in aortic rings incubated with red blood cells (RBCs) from anemic patients. In the aortic rings from anemic mice, the role of arginases was assessed using either an arginase inhibitor (Nor-NOHA) or genetic ablation of arginase 1 in the endothelium. Inflammatory changes in plasma of CA mice were examined by ELISA. Expression of endothelial NO synthase (eNOS), inducible NO synthase (iNOS), myeloperoxidase (MPO), 3-Nitrotyrosine levels, and 4-Hydroxynonenal (4-HNE) were assessed either by Western blotting or immunohistochemistry. The role of reactive oxygen species (ROS) in ED was assessed in the anemic mice either supplemented with N-Acetyl cysteine (NAC) or by in vitro pharmacological inhibition of MPO. The FMD responses were diminished with a correlation to the duration of anemia. Aortic rings from CA mice showed reduced NO-dependent relaxation compared to non-anemic mice. RBCs from anemic patients attenuated NO-dependent relaxation responses in murine aortic rings compared to non-anemic controls. CA results in increased plasma VCAM-1, ICAM-1 levels, and an increased iNOS expression in aortic vascular smooth muscle cells. Arginases inhibition or arginase1 deletion did not improve ED in anemic mice. Increased expression of MPO and 4-HNE observed in endothelial cells of aortic sections from CA mice. NAC supplementation or inhibition of MPO improved relaxation responses in CA mice. Chronic anemia is associated with progressive endothelial dysfunction evidenced by activation of the endothelium mediated by systemic inflammation, increased iNOS activity, and ROS production in the arterial wall. ROS scavenger (NAC) supplementation or MPO inhibition are potential therapeutic options to reverse the devastating endothelial dysfunction in chronic anemia.

Impact of biological sex on the acute flow-mediated dilation response to maximal exercise in healthy older adults

Flow-mediated dilation (FMD) is a noninvasive measure of endothelial function and is a predictor of future cardiovascular disease risk. Previous studies have shown that biological sex modulates the FMD response to acute submaximal exercise in healthy older adults. However, the FMD response to maximal exercise has not been investigated in older adults; thus, whether sex impacts this response remains unknown. Therefore, the purpose of this study was twofold: 1) to investigate the FMD response to maximal exercise in older adults and 2) to test the hypothesis that FMD following maximal exercise will change differently in healthy older men compared with women. We studied twenty sedentary adults (50% women, age: 66±1 vs. 66±1 yrs, men vs. women, mean±SE, P>0.9), free of major clinical disease, who were not on hormone replacement therapy. Women were all postmenopausal. Vascular function was assessed before and after maximal exercise, based on a modified Balke treadmill test. FMD was assessed in response to 5 min forearm occlusion at 250 mmHg using brachial artery ultrasonography. We found pre-occlusion brachial diameter was larger in older men compared with women before (5.04±0.18 vs. 4.27±0.09 mm, P=0.002) and after maximal exercise (4.75±0.16 vs. 3.98±0.12 mm, P=0.001), but there was no sex × time interaction (P=0.1). Peak shear rate was significantly lower in older men compared with women before exercise (1852±81 vs. 2265±129 sec-1, P=0.01) and did not change after maximal exercise in either group (P=0.2). FMD was not significantly different in older men compared with women (P=0.1) before exercise and significantly increased following maximal exercise in both older men (3.84±0.66 vs. 6.55±1.27 %, pre- vs. post-exercise, P=0.009) and women (2.32±0.61 vs. 5.65±1.07 %, P=0.002), but the response was not impacted by sex (P=0.6 for sex × time interaction). When FMD was allometrically scaled to assess the potential effect of pre-occlusion diameter, our findings remained unchanged. Time to peak dilation was delayed in older men and women similarly following maximal exercise (51±2 vs. 75±7 and 56±7 vs. 85±7 sec, pre- vs. post-exercise, P≤0.02; P=0.7 for sex × time interaction). In conclusion, this investigation demonstrated for the first time in older adults that: 1) FMD is enhanced following maximal exercise and 2) biological sex does not influence the FMD response to maximal exercise This work was supported by National Institute of Aging grant AG063143-01. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Particulate Matter 2.5 Level Modulates Brachial Artery Flow-Mediated Dilation Response to Aerobic Exercise in Healthy Young Men

Particulate matter 2.5 (PM2.5) is an environmental pollutant linked with the risk of cardiovascular disease. Aerobic exercise performed in polluted environments may have fewer benefits because of increased PM2.5 inhalation during exercise. However, the vascular responses to aerobic exercise in high PM2.5 (HPM2.5) conditions remain unknown. This study aimed to examine the acute flow-mediated dilation (FMD) response to moderate-intensity treadmill running in HPM2.5 levels compared to low PM2.5 (LPM2.5) levels in healthy young males. Treadmill running in both HPM2.5 and LPM2.5 levels was completed by nine subjects. Brachial artery FMD was measured before and after the exercise to assess vascular endothelial function. Indoor PM2.5 concentration was significantly higher in HPM2.5 than in LPM2.5 conditions (p < 0.001). Scaled FMD significantly increased after the exercise in LPM2.5 conditions but not in HPM2.5 (p = 0.03), and baseline diameter increased only in HPM2.5 conditions after the exercise (p = 0.001). Baseline diameter and peak diameter were smaller, and time to peak dilation was delayed in HPM2.5 compared to LPM2.5 in pre-exercise intervention measurements (p < 0.05). Therefore, acute PM2.5 exposure can counteract the positive effect of aerobic exercise on vascular endothelial function in young males.

Endothelial dysfunction in children with newly diagnosed Graves’ disease

The most frequent cause of hyperthyroidism in children is Graves’ disease (GD). Vascular endothelium is a specific target of thyroid hormone. The purpose of this study is to assess flow-mediated dilatation (FMD)% and serum von Willebrand factor (vWF) levels in children with newly diagnosed GD to reflect the extent of endothelial dysfunction in those children. In this study, 40 children with newly discovered GD and 40 children who were healthy served as the control group. Both patients and controls had anthropometric assessment, as well as measurements of fasting lipids, glucose, insulin, high-sensitivity C-reactive protein (hs-CRP), TSH, and free thyroxine (FT4 and FT3), thyrotropin receptor antibodies TRAbs and vWF. Noninvasive ultrasound was utilized to quantify the carotid arteries’ intima-media thickness and the brachial artery’s FMD. Patients reported significantly reduced FMD response and greater vWF and hs-CRP levels compared to controls (P = 0.001 for each). In multivariate analysis, we reported that vWF was significantly correlated with TSH (OR 2.5, 95% CI 1.32–5.32, P = 0.001), FT3 (OR 3.4, 95% CI 1.45–3.55, P = 0.001), TRAb (OR 2.1, 95% CI 1.16–2.23, P = 0.01), and FMD% (OR 4.2, 95% CI 1.18–8.23, P = 0.001). Conclusions: Children with newly diagnosed GD have endothelial dysfunction, which is shown by impaired FMD and increased vWF. These findings support the idea that GD may need to be treated as soon as possible.What is Known:• Graves' disease is the most common cause of hyperthyroidism in children.• vWF is a reliable marker for detection of vascular endothelial dysfunction.What is New:• Children with newly diagnosed Graves' disease may have endothelial dysfunction as reflected by impairment of FMD and raised vWF level.• Measurement of vWF level in children with newly diagnosed Graves' disease can be used for early detection of endothelial dysfunction.

Tetrodotoxin Decreases the Contractility of Mesenteric Arteries, Revealing the Contribution of Voltage-Gated Na+ Channels in Vascular Tone Regulation.

Tetrodotoxin (TTX) poisoning through the consumption of contaminated fish leads to lethal symptoms, including severe hypotension. This TTX-induced hypotension is likely due to the downfall of peripheral arterial resistance through direct or indirect effects on adrenergic signaling. TTX is a high-affinity blocker of voltage-gated Na+ (NaV) channels. In arteries, NaV channels are expressed in sympathetic nerve endings, both in the intima and media. In this present work, we aimed to decipher the role of NaV channels in vascular tone using TTX. We first characterized the expression of NaV channels in the aorta, a model of conduction arteries, and in mesenteric arteries (MA), a model of resistance arteries, in C57Bl/6J mice, by Western blot, immunochemistry, and absolute RT-qPCR. Our data showed that these channels are expressed in both endothelium and media of aorta and MA, in which scn2a and scn1b were the most abundant transcripts, suggesting that murine vascular NaV channels consist of NaV1.2 channel subtype with NaVβ1 auxiliary subunit. Using myography, we showed that TTX (1 µM) induced complete vasorelaxation in MA in the presence of veratridine and cocktails of antagonists (prazosin and atropine with or without suramin) that suppressed the effects of neurotransmitter release. In addition, TTX (1 µM) strongly potentiated the flow-mediated dilation response of isolated MA. Altogether, our data showed that TTX blocks NaV channels in resistance arteries and consecutively decreases vascular tone. This could explain the drop in total peripheral resistance observed during mammal tetrodotoxications.

The associations of markers of endothelial dysfunction with hip fracture risk.

Endothelial dysfunction underlies the development of atherosclerotic vascular disease. Vascular disease, in turn, is associated with the risk of osteoporotic fractures, such as hip fractures. Here, we examine whether two measures of endothelial dysfunction are related to hip fracture risk. Participants for this study were 2792 individuals (mean age 78.6years) who had flow-mediated dilation (FMD) measured after ischemia in the forearm and 2255 adults (mean age 73.3years) with measured soluble intercellular adhesion molecule (siCAM) levels, a constitutive endothelial cell membrane protein associated with the initiation of atherosclerosis. Mean follow-up was 9.7 and 11.7years, respectively. There were 375 and 265 incident hip fractures, respectively, in each group. In Cox proportional hazards models, there was no significant association between FMD response and incident hip fracture (HR per 1% higher FMD was 0.98 [0.93, 1.04]; p = 0.44). In exploratory analyses, when data were examined dichotomously, participants in the lowest 80% of FMD (≤ 4.5%) had an adjusted 1.29 (0.98, 1.68; p = 0.067) higher hazard of hip fracture compared to participants in the upper 20% of FMD change. There were no significant associations between siCAM and incident hip fracture whether examined as a continuous or dichotomized variable. Among older adults, two measures of endothelial dysfunction were not significantly associated with hip fracture risk. There was a trend for higher fracture risk with lower FMD.

Abstract P121: Varying Determinants of Endothelial Dysfunction by Age Group Among Mexican Americans

Endothelial dysfunction assessed by impaired brachial flow-mediated dilation (FMD) is a predictive factor of incident CVD. Most studies included small proportions of Hispanics or Latinos. We aimed to assess determinants of impaired FMD in a large population-based sample of asymptomatic Mexican-Americans. Methods: Cardiometabolic biomarkers, visceral adipose tissue (VAT), and FMD were obtained from 960 participants (57.9% females, mean age 52.1±0.9 years, age 18-85 years) from the Cameron County Hispanic Cohort. Sex-specific median values of %FMD were used to divide participants into two groups: those with FMD below (low %FMD) and above the median (high %FMD). The sample was further stratified into younger (age<55 years) and older (age ≥ 55 years) age groups. Survey-weighted logistic regression analyses were conducted to evaluate the effects of factors on the %FMD groups. Results: There was a high prevalence of obesity (49.1%), hypertension (47.8%), diabetes (26.1%), hypercholesterolemia (46.7%), and metabolic syndrome (38.2%). The median FMD response was 4.2%±0.3% [3.8% (SE 0.4) in males and 4.5% (SE 0.4) in females]. Low %FMD group was significantly older, had higher VAT, SBP, or plasma glucose levels, and had metabolic syndrome compared to those in the high %FMD group. Multivariable-adjusted age-stratified logistic regression analyses showed that among older participants, male gender [OR =2.4 (1.4-4.2)] and having hypertension [OR=2.3 (1.3-4.3)] or pre-diabetes [OR=3.4 (1.5-7.5)] remained significantly associated with odds of low %FMD. Among younger participants, only high LDL [OR=2.8 (1.6-4.9)] or having metabolic syndrome [OR=1.9 (1.1-3.6)] were significantly associated with odds of low %FMD. Conclusion: We found age-dependent associations between cardiometabolic biomarkers and an FMD response below the gender-specific median in a population composed of Mexican-Americans without prior CVD. Targeting specific risk factors by age may mitigate progression to incident CVD in this high-risk group.

PS-P07-7: IMPACT OF INORGANIC NITRATE ON ENDOTHELIAL FUNCTION IN ADULTS A SYSTEMATIC REVIEW OF RANDOMISED CONTROLLED TRIALS AND META ANALYSIS

Aim: Inorganic nitrate which is found in green leafy vegetables and beetroot reduces blood pressure via the nitrate-nitrite-NO pathway and may have other benefits such as improved endothelial function. It is assumed that endothelial dysfunction is key risk factor for CVDs. Therefore, in this systematic review and meta-analysis, we evaluated the impact of inorganic nitrate supplementation on endothelial function. Design and method: MEDLINE, Web of Science, and Scopus databases were searched by two independent authors up to November 2021. We included randomised controlled trials that test oral administration of dietary/non-dietary inorganic nitrate versus a control, adult male and female subjects with/without health conditions, measuring endothelial function by flow mediated dilatation (FMD) as an outcome. Risk and quality assessments were performed using a Cochrane risk of bias score and standardised mean differences of the outcomes were pooled using a random-effects model. Results: 3,521 studies were identified after a database search, of which 12 studies met the inclusion criteria. The pooled sample size was 362 and the number of participants per trial ranged from 10 to 65. Eight studies were acute, four studies were chronic and most of them included healthy participant arms (n = 12) with (n = 4) focusing on unhealthy populations. The mean difference in %FMD for nitrate versus the control was 1.57% (95% CI: 0.76–2.37), p = 0.01; high heterogeneity (I2 = 98.3%) was observed (Figure 1). Subgroup analyses were performed in terms of, nitrate amount (< more or less than 600 mg), type of intervention (dietary or non-dietary), participants health status (healthy and unhealthy), and study duration (acute or chronic). All sub-analysis still showed significant increases in %FMD. In acute studies, FMD response was higher (2.13% (95% CI: 0.87–3.40), p < 0.01, I2 = 98.5%) than chronic studies (0.90% (95% CI: 0.48–1.31), p < 0.01, I2 = 68.6%). Only one study showed low risk of bias; the other studies were classified as “some concern” due to a lack of information about randomisation and lack of pre-specified analysis plans. Conclusions: The meta-analysis provides evidence that inorganic nitrate improves FMD response and may be a useful strategy for preventing further CVD. Change in 1.5% of FMD as seen in this review could results in a reduction in CVD risk of ∼15%. However, due to the high heterogeneity of the results, further studies are needed to build a robust evidence base to inform dietary recommendations.

Macro- and Microvascular Function in Middle-Aged Individuals with Low Cardiovascular Disease Risk.

Aims: To investigate the microvascular function in apparently healthy individuals showing signs of early macrovascular endothelial dysfunction. Methods: Healthy participants aged between 30−55 years were recruited for the present study. Baseline measurements included body-mass index (BMI), waist-to-hip ratio (WHR), 24-h blood pressure, as well as fasted venous glucose, triglycerides (TG) and cholesterol (HDL, LDL and total). Brachial artery reactivity was measured using the flow-mediated dilation (FMD) technique and retinal vessel reactivity was assessed by using the Dynamic Retinal Vessel Analyser (DVA) in all individuals. The enrolled participants were separated in two groups, based on either a reduced (group 1: <5%—n = 53) or a normal FMD response (group 2: 7−10%—n = 47). Results: Individuals exhibiting reduced FMD responses showed a reduced baseline-corrected microvascular arterial dilation response to flickering light (p = 0.039). In addition, they also exhibited a reduced arteriolar maximum dilation (p = 0.034), as well as a longer dilation reaction time (p = 0.048) and a lower dilation amplitude (p = 0.042) when compared to those with normal FMD values. Conclusion: In otherwise healthy middle-aged individuals, early signs of vascular dysfunction are reflected simultaneously at both macro- and microvascular levels.

Correlation Of Urine Albumin Creatinine Ratio And C-Reactive Protein Levels on Carotid Artery Intima-Media Thickness And Flow-Mediated Dilatation Response In Children and Adolescent with Type 1 Diabetes Mellitus At Dr Saiful Anwar Hospital Malang

Background: Early and accelerated atherosclerosis is a major cause of cardiovascular disease and often causes premature death in T1DM patients. In T1DM, atherosclerosis can be detected since adolescence. The initial association between urinary albumin to creatinine ratio (ACR) and c-reactive protein (hs-CRP) with subclinical cardiovascular disease in children and adolescents with T1DM supported findings from previous studies. Imaging tests using ultrasound can detect subclinical atherosclerosis in this patient population. Carotid artery intima-me- dia thickness (cIMT) and flow-mediated dilatation response (FMD) have been frequently used to detect subclini- cal atherosclerosis. Objectives: To find correlation between ACR and hsCRP on the thickness values of cIMT and FMD in children and adolescent T1DM patients at Dr Saiful Anwar Hospital Malang Methods: This is a cross-sectional study with 82 subjects of T1DM patients who routinely control the pediatric outpatient clinic of RSUD Dr. Saiful Anwar Malang, with the research period January – July 2019 and December 2021 – March 2022. Subjects were undergone valcuras ultrasound examination for measurements of cIMT and FMD. Blood sample from subjects were also collected to detect level of ACR and hsCRP. Associations between the study variables were estimated by calculating the Pearson’s rank correlation. Result: There was correlation between ACR with FMD and cIMT (r=-0.593; p=0.000 and r=0.339; p=0.002, respectively). ACR was negatively correlated with FMD and positively correlated with cIMT. There was also correlation between hsCRP with FMD and cIMT (p=-0.375; p=0.001 and r= 0.414; p=0.023, respectively). hsCRP was negatively correlated with FMD and positively correlated with cIMT. Conclusion: ACR and hsCRP have a correlation with increasing CIMT values and decreasing FMD values in children and adolescents with T1DM patients. Preadolescent children with T1DM displayed evidence of increased low-intensity vascular inflammation, increased cIMT and attenuated FMD measurements. These data suggest that endothelial dysfunction and systemic inflammation are present even in preadolescent children with T1DM

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

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

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.

The Effect of Meals Containing Culinary Doses of Spices on Postprandial Endothelial Function, Lipemia and Glycemia: A Randomized, Crossover, Controlled-Feeding Study

ObjectivesThe objective was to examine the effect of meals containing 0.6 g (low-spice meal), 3.7 g (moderate-spice meal), and 7.4 g (high-spice meal) of herbs/spices on postprandial flow mediated dilation (FMD), triglycerides, insulin and glucose in men and post-menopausal women at-risk for cardiovascular disease. MethodsA 3-period, randomized, crossover, controlled-feeding study was conducted. Participants consumed an average American diet containing 0.5 (low-spice diet), 3.3 (moderate-spice diet), and 6.6 (high-spice diet) g/d/2100 kcal of herbs and spices for 4-weeks. At baseline and the end of each diet period, participants were given a meal challenge (1192 kcal; carbohydrate 145 g; protein 62 g; fat 44 g; saturated fat 20 g). The spice dose in the test meal corresponded to the spice level of the diet consumed for the previous 4 weeks. Blood was sampled at 0, 30, 60, 120, 180, 240 minutes for analysis of triglycerides, glucose, and insulin. FMD was measured at 0,120 and 240 minutes. ResultsThe analytic sample included 43 participants (males 65%; age 48 ± 11 years; BMI 28.9 ± 2.9 kg/m2, FMD 6.2 ± 2.3%). No between-meal differences were observed for FMD (meal P = 0.30; time P < 0.001; meal by time interaction P > 0.99). The area under the curve for triglycerides (P = 0.39), glucose (P = 0.49) and insulin (P = 0.07) was not different between the meals. ConclusionsFollowing intake of an average American diet with three different doses of spices (0.5, 3.3 and 6.6 g/d/2100 kcal) for 4-weeks, FMD, triglyceride, glucose and insulin responses to meals containing 0.6 g, 3.7 g and 7.4 g of spices were not different. These findings suggest that following 4-weeks of exposure to spice-containing diets, spice exposure from a meal does not dose-dependently affect endothelial function, lipemia and glucose homeostasis in the 4-hours post meal. Funding SourcesMcCormick Science Institute; National Center for Advancing Translational Sciences, National Institutes of Health, through Grant UL1 TR002014.

The Impact of Exercise Training Interventions on Flow-Mediated Dilation: An Umbrella Review Protocol

Introduction. (Cardio)vascular diseases are among the top causes of death in western societies. The impact of exercise training interventions to improve endothelial-dependent, flow-mediated dilation (FMD) responses has been reviewed extensively. These reviews may differ in their inclusion criteria, exercise type, exercise mode, exercise intensity, specific research questions, and conclusions. Comparing and contrasting these reviews will assist with the determination of optimal exercise programs across healthy and clinical populations.Objectives. We will conduct an umbrella review (or review of reviews) on systematic reviews and meta-analyses that examined the impact of exercise training interventions on peripheral artery FMD. The impact of exercise training design, population or artery studied, FMD methodology, and quality of reviews will be explored.Methods. A database search will be conducted in Scopus, EMBASE, MEDLINE, CINAHL, and Academic Search Premier for systematic reviews and meta-analyses on exercise training and FMD. All reviews must be conducted in adults (≥18 years). No limitation will be placed on the population (disease status, sex, etc.) or type of exercise training. Study quality will be determined using the Joanna Briggs Institute critical appraisal checklist for systematic reviews. Two independent screeners will examine titles, abstracts, full texts of relevant sources, and conduct the quality assessments. The results will be presented narratively and in a tabular format to align with the review objectives.Conclusion. This umbrella review may provide insight into the optimal training program to improve arterial health and act as an agent of change for modifying existing community exercise programs or clinical rehabilitation programs.

Cerebrovascular Function, Vascular Risk, and Lifestyle Patterns in Resistant Hypertension.

Impaired cerebrovascular reactivity (CVR) and blunted cerebral hemodynamic recruitment are thought to be important mechanisms linking hypertension to cerebrovascular and cognitive outcomes. Few studies have examined cardiovascular or dietary correlates of CVR among hypertensives. To delineate associations between cardiometabolic risk, diet, and cerebrovascular functioning among individuals with resistant hypertension from the TRIUMPH trial (n = 140). CVR was assessed by examining changes in tissue oxygenation (tissue oxygenation index [TOI] and oxygenated hemoglobin [HBO2]) using functional near-infrared spectroscopy (fNIRS) during a breath holding test, a standardized CVR assessment to elicit a hypercapnic response. Participants also underwent fNIRS during three cognitive challenge tasks. Vascular function was assessed by measurement of brachial artery flow-mediated dilation and hyperemic flow response. Cardiometabolic fitness was assessed from peak VO2 on an exercise treadmill test and body mass index. Dietary patterns were quantified using the DASH eating score. Cognitive function was assessed using a 45-minute test battery assessing Executive Function, Processing Speed, and Memory. Greater levels fitness (B = 0.30, p = 0.011), DASH compliance (B = 0.19, p = 0.045), and lower obesity (B = -0.30, p = 0.004), associated with greater changes in TOI, whereas greater flow-mediated dilation (B = 0.19, p = 0.031) and lower stroke risk (B = -0.19, p = 0.049) associated with greater HBO2. Similar associations were found for cerebral hemodynamic recruitment, and associations between CVR and cognition were moderated by duration of hypertension. Impaired CVR elevated cardiometabolic risk, obesity, vascular function, and fitness among hypertensives.

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.

Endothelial (Dys)function in Women With Androgen Excess Polycystic Ovary Syndrome: Effects of Body Composition and Ethinyl Estradiol Supplementation

Polycystic ovary syndrome (PCOS) has been associated with endothelial dysfunction. However, whether endothelial dysfunction occurs as a result of obesity in androgen excess PCOS (AE‐PCOS) remains unclear. The purpose of this study was to compare endothelial function between lean and overweight/obese (OW/OB) women with AE‐PCOS. We hypothesis that OW/OB women with AE‐PCOS would demonstrate impaired endothelial function relative to lean women with AE‐PCOS as well as both lean and OW/OB controls without any form of PCOS. We also tested the hypothesis that short‐term ethinyl estradiol (EE) supplementation improves endothelial function in both lean and OW/OB women with AE‐PCOS. We assessed conduit vessel endothelial function in 14 women with AE‐PCOS (lean: n=7; OW/OB: n=7) and 12 controls (CTRL; lean: n=6, OW/OB: n=6) using flow‐mediated dilation (FMD). FMD responses were assessed twice: before (baseline; BSL) and on the last day of 7‐day oral EE (post‐EE; 30mg/day) and quantified as the peak increase in diameter during reactive hyperemia (%FMD), shear rate, and low flow‐mediated vasoconstriction (LFMC). BSL %FMD was attenuated in lean AE‐PCOS relative to both lean CTRL (5.2 ± 1.5% vs10.3 ± 2.6%, P&lt;0.01) and OW/OB AE‐PCOS (5.2 ± 1.5% vs6.6 ± 0.9%, P=0.04). A negative correlation between BSL %FMD and free testosterone was observed in lean AE‐PCOS only (R2=0.68, P=0.02). %FMD was unchanged from BSL to post‐EE in lean AE‐PCOS (5.17±1.5 vs5.17±1.1, P=0.99). Post‐EE, %FMD was lower in lean CTRL (10.3±2.6% vs7.6±1.2%, P=0.03), but increased in both OW/OB CTRL (7.3±0.1.2% vs 10.4±2.5%) and OW/OB women with AE‐PCOS (6.6±0.92% vs 9.6±1.7%; main effect of EE, P&lt;0.01). Post‐EE %FMD changes from BSL were associated with EE‐induced changes in LFMC and shear rate. Our data indicate that lean women with AE‐PCOS exhibit more severe conduit vessel endothelial dysfunction than OW/OB women with AE‐PCOS. Our data also indicate that short‐term EE supplementation affects LFMC and shear rate (and therefore %FMD) differently across healthy lean women and OW/OB women with and without AE‐PCOS.