Brachial Artery FMD Research Articles

Home-Based Heat Therapy and Vascular Function of Adults Living with Type 2 Diabetes: Preliminary Analyses of a Randomized Controlled Trial

Background: Several studies indicate that various heat exposure interventions improve peripheral endothelial function and microvascular reactivity, as well as reduce central arterial stiffness and blood pressure in various populations. Nonetheless, few studies have considered the potential therapeutic effects of heat exposure for people living with type 2 diabetes mellitus (T2DM), who are at high cardiovascular risk. In addition, all heat therapy interventions investigated to date have been laboratory-based, which may limit long-term adherence. HYPOTHESES: This study aims is to determine the effects of a 12-week home-based heat therapy intervention on markers of vascular function in adults living with T2DM. The primary hypothesis is that heat therapy improves peripheral endothelial function relative to a sham intervention. Secondary hypotheses include improved microvascular reactivity, central arterial stiffness, and 24h blood pressure. METHODS: Thirteen adults (66 ± 10 years, 28.9 ± 6.0 kg/m2, 9 men/ 4 women) living with TD2M were randomized to 12 weeks of home-based heat therapy (n=7, lower leg immersion in 42°C water) or a thermoneutral sham intervention (n=6, lower leg immersion in 36°C water). Peripheral endothelial function (brachial artery flow-mediated dilation, FMD), microvascular reactivity (post-occlusive reactive hyperemia), arterial stiffness (carotid-femoral pulse wave velocity), and 24h blood pressure (ambulatory blood pressure monitoring), were measured before and after the intervention. RESULTS: Brachial artery FMD changed by 1.72% [95%CI, 0.06; 3.37] in response to heat therapy compared to 0.41% [-1.38; +2.20] in response to the sham intervention. Peak and total reactive hyperemia changed by 0.79 mL/min/mmHg [-0.27; 1.86] and by 1.77 mL/mmHg [0.73; 2.81], respectively, in response to heat therapy compared with 0.76 mL/min/mmHg [-0.38; 1.91] and 1.68 mL/mmHg [0.56; 2.80] in response to the sham intervention. Arterial stiffness changed by 0.55 m/s [-1.62; 2.71] in response to heat therapy compared with -1.60 m/s [-3.75; 0.57] in response to the sham intervention. The 24h-systolic and diastolic blood pressure changed by 6 mmHg [-1; +12] and 2 mmHg [-3; +7], respectively, in response to heat therapy compared with -2 mmHg [-10; +6] and -3 mmHg [-9; +3] in response to the sham intervention. CONCLUSION: These preliminary results suggest that 12 weeks of home-based lower leg hot water immersion improves brachial artery FMD in adults with T2DM. In contrast, the heat therapy intervention does not appear to improve microvascular reactivity, central arterial stiffness, or 24h blood pressure. Cardiometabolic Health Diabetes and Obesity Research Network and Diabète Quebec. This is the full abstract presented at the American Physiology Summit 2024 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.

Acute and chronic hyperglycemia blunts microvascular reactivity in postmenopausal women with type 2 diabetes

Type 2 diabetes (T2D) is strongly associated with increased risk of cardiovascular diseases via endothelial dysfunction. Hyperglycemia causes microvascular endothelial dysfunction and reduces muscle perfusion. Near-infrared spectroscopy (NIRS) measures microvascular reactivity in skeletal muscle during vascular occlusion/reperfusion. However, the impact of acute and chronic hyperglycemia on macrovascular endothelial function (brachial flow-mediated dilation, FMD) and microvascular reactivity (NIRS-derived tissue oxygen saturation index, TOI) has not been examined in postmenopausal women with and without T2D. We hypothesized that T2D women would have decreased FMD and TOI responsiveness in the fasted condition and greater vascular impairments during acute hyperglycemia compared to controls.Ten T2D (61 ± 5 years) and 10 normoglycemic postmenopausal women (CON, 62 ± 7 years) participated in the study. Hemoglobin A1C (HbA1C) and blood glucose were measured by finger prick at baseline (fasted condition). Brachial artery FMD was evaluated using ultrasound. Forearm muscle TOI magnitude and slope during arterial occlusion and reperfusion periods were measured using NIRS. An oral glucose tolerance test (OGTT) was performed to induce acute hyperglycemia. Blood glucose, FMD, and TOI were measure at baseline and 1 hour (1-h) after OGTT. Abdominal fat was assessed by waist circumference and visceral adipose tissue (VAT) obtained by a whole-body dual-energy X-ray absorptiometry scan.Fasting HbA1C and glucose, waist circumference, and VAT were higher in T2D compared to CON (all p < 0.05). The increase in blood glucose at 1-h was higher in T2D (Δ143 ± 15 mg/dl) compared to CON (Δ49 ± 5 mg/dl) (p < 0.01). FMD at baseline and the decreases in FMD at 1-h were similar in T2D (Δ-2.2 ± 0.2%) and CON groups (Δ-1.9 ± 0.4%) (all p < 0.01). At baseline, T2D showed blunted TOI occlusion magnitude (T2D: -16 ± 1 vs. CON: -21 ± 2%), TOI occlusion slope (T2D: -0.05 ± 0.01 vs. CON: -0.07 ± 0.01), TOI reperfusion magnitude (T2D: 21 ± 2 vs. CON: 32 ± 3%), and TOI reperfusion slope (T2D: 0.79 ± 0.10 vs. CON: 1.19 ± 0.14) compared to CON (all p < 0.05). At 1-h, T2D exhibited lower TOI occlusion magnitude (T2D: -17 ± 2 vs. CON: -24 ± 3%), TOI occlusion slope (T2D: -0.06 ± 0.01 vs. CON: -0.08 ± 0.01), TOI reperfusion magnitude (T2D: 23 ± 2 vs. CON: 33 ± 4%), and TOI reperfusion slope (T2D: 0.90 ± 0.19 vs. CON: 1.14 ± 0.15) compared to CON (all p < 0.05). HbA1C, a measure of chronic hyperglycemia, was positively correlated with VAT (r = 0.514, p = 0.02) and TOI occlusion slope (r = 0.460, p = 0.04) and negatively correlated with TOI reperfusion magnitude (r = -0.506, p = 0.02) and slope at baseline (r = -0.493, p = 0.03). In conclusion, women with T2D exhibited blunted microvascular reactivity despite similar FMD compared with normoglycemic women in the fasted condition. Acute hyperglycemia further blunted microvascular function, but not macrovascular endothelial function, in women with T2D. Blunted microvascular reactivity was associated with chronic hyperglycemia and elevated VAT in postmenopausal women. This is the full abstract presented at the American Physiology Summit 2024 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.

The prognostic role of galectin-3 and endothelial function in patients with heart failure.

Heart failure (HF) is nowadays classified as HF with reduced ejection fraction (HFrEF), HF with mildly reduced EF (HFmrEF), and HF with preserved EF (HFpEF). Endothelial dysfunction (assessed by flow-mediated dilatation [FMD]), increased arterial stiffness (assessed by carotid-femoral pulse-wave velocity [PWV]), and galectin-3, a biomarker of myocardial fibrosis, have been linked to major adverse cardiovascular events (MACE) in patients with ischemic HF. In this study we prospectively enrolled 340 patients with stable ischemic HF. We assessed the brachial artery FMD, carotid-femoral PWV, and galectin-3 levels, and patients were followed up for MACE according to HF group. Interestingly, the FMD values exhibited a stepwise improvement according to left ventricular ejection fraction (LVEF) (HFrEF: 4.74 ± 2.35% vs. HFmrEF: 4.97 ± 2.81% vs. HFpEF: 5.94 ± ± 3.46%, p = 0.01), which remained significant after the evaluation of possible confounders including age, sex, cardiovascular risk factors, and number of significantly stenosed epicardial coronary arteries (b coefficient: 0.990, 95% confidence interval: 0.166-1.814, p = 0.019). Single-vessel coronary artery disease was more frequent in the group of HFpEF (HFrEF: 56% vs. HFmrEF: 64% vs. HFpEF: 73%, p = 0.049). PWV did not display any association with LVEF. Patients who presented MACE exhibited worse FMD values (4.51 ± 2.35% vs. 5.32 ± 2.67%, p = 0.02), and the highest tertile of galectin-3 was linked to more MACEs (36% vs. 5.9%, p = 0.01). Flow-mediated dilatation displayed a linear improvement with LVEF in patients with ischemic HF. Deteriorated values are associated with MACE. Higher levels of galectin-3 might be used for risk stratification of patients with ischemic HF.

Comparing hs-CRP and MPO Biomarkers of Subclinical Atherosclerosis in Metabolic Syndrome Patients

Cardiovascular disorders have been linked to myeloperoxidase, an enzyme generated from leukocytes. MPO creates an antibacterial system and has been many correlations between MPO, hs-CRP and cardiovascular disease. The present study has aimed to assess MPO, hs-CRP and subclinical atherosclerosis in metabolic syndrome patients by using FMD and CIMT parameters. 75 metabolic syndrome affected patients had defined as per the criteria of IDF (International Diabetes Federation) which had been in this study. In addition, ultrasound doppler had been employed for determining the carotid intima medial thickness for both right and left (left and right CIMT) and brachial artery FMD. By employing the Immunoassay MPO and hs-CRP ultrasensitive ELISA kit, the concentration of MPO and hs-CRP is measured. A positive link between MPO with CIMT right and left (r value of right CIMT=0.723, p <0.05 and left CIMT r=0.712, p<0.01), hs-CRP with CIMT right and left (r value of right CIMT=0.613, p<0.05and left CIMT r=0.64, p<0.01)and a significant inverse correlation between MPO with FMD (r= -0.319,p<0.05), hs-CRP with FMD (r= -0.304,p<0.01) in metabolic syndrome patients. Serum MPO and hs-CRP is positively linked with subclinical atherosclerosis in metabolic syndrome patients. According to this finding, understanding the mechanism behind the risk factors for cardiovascular disease can be aided by the development of new molecular markers for metabolic syndrome and subclinical atherosclerosis.

The utility of the reperfusion rate of tissue oxygen saturation as a measure of vascular endothelial function in adolescents: reliability, validity and sensitivity.

Introduction: The near-infrared spectroscopy (NIRS)-derived reperfusion rate of tissue oxygen saturation (slope 2 StO2) may provide a surrogate measure of vascular function, however, this has yet to be examined in a paediatric population. This study investigated in adolescents: 1) the between-day reliability of NIRS-derived measurements; 2) the relationship between slope 2 StO2 and macro- (flow-mediated dilation, FMD) and microvascular (peak reactive hyperaemia, PRH) function; and 3) the effect of high-intensity interval exercise (HIIE) on slope 2 StO2, FMD, and PRH. Methods: Nineteen boys (13.3 ± 0.5 y) visited the laboratory on two occasions, separated by ∼ 1week. On visit 1, participants underwent simultaneous assessment of brachial artery FMD and slope 2 StO2 and PRH on the internal face of the forearm. On visit 2, participants completed a bout of HIIE with slope 2 StO2, FMD and PRH measured pre-, immediately post- and 1.5h post-exercise. Results: Slope 2 StO2 showed no mean bias (p = 0.18) and an intraclass correlation coefficient of 0.67 (p = 0.003) between visits. No significant correlation between slope 2 StO2 and FMD or PRH was observed on visit 1 (r = -0.04, p = 0.89 and r = -0.30, p = 0.23, respectively) or visit 2 pre-exercise (r = -0.28, p = 0.25 and r = -0.31, p = 0.20, respectively). Compared to pre-exercise, FMD decreased immediately post-exercise (p < 0.001) and then increased 1.5h post-exercise (p < 0.001). No significant change was detected for slope 2 StO2 (p = 0.30) or PRH (p = 0.55) following HIIE. Conclusion: In adolescents, slope 2 StO2 can be measured reliably, however, it is not correlated with FMD or PRH and does not follow the acute time course of changes in FMD post-exercise. Hence, the use of slope 2 StO2 as a surrogate measure of vascular function in youth must be refuted.

ENDOTHELIAL FUNCTIONAL STATUS IN PATIENTS WITH HYPERTENSION AND TYPE 2 DIABETES MELLITUS AFTER COVID-19

Objective: Aim of the study was to estimate endothelial functional status in patients with hypertension and type 2 diabetes mellitus (T2DM) who underwent Covid-19. Design and method: 56 patients with hypertension and T2DM after coronavirus infection (Group I) and 56 patients with hypertension and T2DM without any history of Covid-19 (Group II) were enrolled in this study. Group I patients aged 43-75 years, mean age 62.4±12.5 years; male = 46% and Group II patients aged 42-77 years, mean age 63.6±13.7 years; male = 43%. Endothelial functional status was assessed by flow-mediated vasodilation of brachial artery (FMD). All statistical analysis were performed by SPSS 26.0 software. Results: FMD of brachial artery was significantly decreased in patients with hypertension and T2DM after Covid-19 than those patients without Covid-19 (P&lt;0.01). There were a correlation between Covid-19 and reduced FMD in Group I (r = 0.7, CI 95%, P = 0.032). When we assessed systolic function of the left ventricle, there were a positive correlation between reduced FMD and low ejection fraction (r = 0.6, CI 95%, P = 0.028), however this correlation were more pronounced in Group I (P = 0.001). Multivariate analysis revealed that reduced flow-mediated vasodilation of brachial artery was independent predictor of poor systolic function of patients with hypertension and T2DM especially in those after Covid-19 (odds ratio [OR] 1.52, P = 0.026). When we separately analyzed between men and women there were not any statistical significant changes between male and female (P&gt;0.05). Conclusions: Patients with hypertension and type 2 diabetes mellitus after Covid-19 had impaired FMD of brachial artery. Even though, there were positive correlation between flow-mediated vasodilation of brachial artery and reduced ejection fraction, patients with hypertension and T2DM after Covid-19 had strong correlation of it. In hypertensive patients with type 2 diabetes mellitus who have undergone Covid-19, FMD independently associated with poor left ventricular systolic function.

Pod-based e-cigarettes versus combustible cigarettes: The impact on peripheral and cerebral vascular function and subjective experiences.

The vaping epidemic in the US has been largely attributed to the emergence of pod-based e-cigarette devices. While these devices continue to be promoted as alternatives to cigarettes, their impact on cardiovascular and behavioral outcomes remains incompletely understood. This study assessed the impact of pod-based e-cigarettes on peripheral and cerebral vascular function, along with subjective experiences among adult cigarette smokers. In a crossover laboratory design study, a total of 19 (e-cigarette naïve) cigarette smokers (aged 21-43 years) attended two lab sessions. In one session, participants smoked a cigarette and in the other, vaped a pod-based e-cigarette. Participants completed questions assessing subjective experiences. Peripheral macrovascular and microvascular function was assessed via brachial artery FMD and reactive hyperemia, while cerebral vascular function was assessed as the blood velocity response of the middle cerebral artery during hypercapnia. Measurements were taken before and after exposure. Compared with baseline, there was a reduction in peripheral macrovascular function (indexed by FMD), following e-cigarette (pre=9.3±4.3%; post=6.4±4.1%) and cigarette use (pre=10.2±3.7%; post=6.8±3.8%; main effect of time p<0.0001). Cerebral vascular function (indexed by cerebral vasodilatory response during hypercapnia) was also reduced following e-cigarette (pre=53±19%; post=44±15%) and cigarette use (pre=54±21%; post=44±17%; main effect of time p<0.01). The magnitude of reduction in peripheral and cerebral vascular function was similar between conditions (condition × time, p>0.05). Compared with vaping an e-cigarette, participants scored higher for measures of satisfaction, taste, puff liking, and suppression of craving following smoking (p>0.05). Similar to smoking, vaping a pod-based e-cigarette leads to an impairment in peripheral and cerebral vascular function while providing a reduced subjective experience compared with a cigarette among adult smokers. While these data challenge the notion that e-cigarette use is a safe and satisfactory alternative to cigarette use, large longitudinal studies are needed to assess the long-term impact of pod-based e-cigarette devices on cardiovascular and behavioral outcomes.

Finnish Sauna Bathing and Vascular Health of Adults with Coronary Artery Disease: a Randomized Controlled Trial

BACKGROUND: Regular Finnish sauna use has been associated with a reduced risk of cardiovascular mortality. However, physiological mechanisms underlying this association remain unknown. Other forms of heat therapy have been shown to improve markers of vascular health in healthy young adults, middle-aged adults with cardiovascular risk factors, and older adults with chronic heart failure. It is unknown if Finnish sauna use elicits similar adaptations. HYPOTHESIS: This study determined if Finnish sauna bathing improves markers of vascular health in adults with coronary artery disease (CAD). We tested the primary hypothesis that 8 weeks of Finish sauna bathing improves peripheral endothelial function. Secondary hypotheses were that Finish sauna bathing improves peripheral microvascular function, central arterial stiffness and blood pressure. METHODS: Forty-one adults (62 ± 6 years, 29.0 ± 4.3 kg/m2, 33 men/8 women) with stable CAD and na&amp;iuml;ve to heat therapy were randomized to 8 weeks of Finnish sauna use (n=21, 4 sessions/week, 20-30 min/session) or control intervention (lifestyle maintenance, n=20). Peripheral endothelial function (brachial artery flow-mediated dilation, FMD), central arterial stiffness (carotid-femoral pulse wave velocity), total (area under the curve) and peak post-occlusion forearm reactive hyperemia, and blood pressure (automated auscultation) were measured before and after the intervention. RESULTS: Brachial artery FMD changed from 4.09 ± 2.05% to 4.24 ± 2.70% in response to sauna bathing and from 4.00 ± 2.02% to 4.10 ± 2.10% in response to the control intervention (p for interaction = 0.95). The change in central arterial stiffness (p for interaction = 0.82), total reactive hyperemia (p for interaction = 0.07), systolic (p for interaction = 0.95) and diastolic (p for interaction = 0.29) blood pressure also did not differ between interventions. The change in peak reactive hyperemia differed between interventions (p for interaction = 0.05) due to a slight decrease in response to sauna bathing (3.03 ± 1.42 to 2.75 ± 1.18 ml/min/mmHg, p=0.76) relative to a slight increase in response to control (2.78 ± 0.98 to 3.24 ± 1.00 ml/min/mmHg, p=0.05). CONCLUSION: These results demonstrate that 4 sessions of Finnish sauna bathing per week for 8 weeks does not improve markers of vascular health in older adults with stable CAD. Heart and Stroke Foundation of Canada, Fonds de Recherche du Québec – Santé 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.

Abstract 13635: Blunted Vascular Endothelial Function in Black Females: Examining the Impact of Psychosocial Stress Exposure versus Internalization and Coping

Introduction: Among females in the United States, Black females suffer from the highest rates of hypertension, coronary artery disease, and total cardiovascular disease (CVD) mortality. Vascular endothelial dysfunction precedes overt CVD and predicts CVD risk and has been reported in this population, but this is not always a consistent finding. Although psychosocial stress from numerous sources likely contributes to this disparity, the precise pathways and mechanisms remain incompletely understood. A growing literature suggests that internalization and coping may be more important than exposure to stressors alone. Therefore, we examined the relationship between endothelial function (brachial artery flow-mediated dilation, FMD) and psychosocial stress exposure (adverse childhood experiences, ACEs; past week discrimination, PWD) versus internalization/coping (John Henryism Active Coping Scale, JHAC12; Giscombe Superwoman Schema Questionnaire, G-SWS-Q). We hypothesized that 1) FMD would be blunted in Black relative to White females and 2) among Black females, internalization and maladaptive coping would exhibit a stronger negative relationship with FMD than exposure to stressful experiences alone. Methods: Twelve Black (21 ± 3 yr) and 8 White (25 ± 6 yr) healthy females underwent standard FMD testing. Black participants completed the ACEs, PWD, JHAC12, and G-SWS-Q inventories. Higher scores indicated greater stressor exposure or endorsement of the internalization/coping constructs. Results: Brachial artery FMD was lower in Black relative to White females (4.93 ± 3.10 vs 8.58 ± 1.62%; p &lt; .01). Neither ACEs ( r = -.10, p = .75) nor PWD ( r = -.24, p = .45) were associated with FMD. JHAC12 scores were ( r = -.61, p = .02) and SWS scores tended to be ( r = -.39, p = .11) negatively associated with FMD. Among the SWS subscales, SWS-Resistance to Being Vulnerable ( r = -.51, p = .04) and SWS-Intense Motivation to Succeed ( r = -.54, p = .04) were negatively associated with FMD. Conclusion: These preliminary data indicate that 1) brachial artery endothelial function is blunted in young Black females and 2) reduced vascular function in Black females may be due more to internalization and maladaptive coping than exposure to stressful experiences alone.

Abstract 12217: Effect of Repeated Binge Drinking in Mid-Life Adults on Vascular Function

Introduction: Age-related changes in vascular function, including endothelial dysfunction and arterial stiffening, contribute to the development of cardiovascular disease. “Mid-life adults”, defined as age 50-64, begin to show signs of vascular aging. One in five mid-life adults engage in binge drinking and our previous studies in young adults showed that repeated binge drinking was associated with endothelial dysfunction and arterial stiffening. However, it is unclear how binge drinking influences vascular function in aged individuals. Therefore, the purpose of this study is to investigate endothelial function and arterial stiffness in mid-life adults who binge drink regularly (binge drinkers) compared to those who did not drink alcohol (alcohol abstainers). Methods: Twelve apparently healthy mid-life men and postmenopausal women, with no smoking history were included in this study (mean±SEM, age: 57±1 years, body mass index: 26.0±0.8 kg/cm 2 , systolic blood pressure: 119±5 mmHg). Alcohol use was assessed by the Alcohol Use Disorders Identification Test (AUDIT) and dried blood spot phosphatidylethanol. Endothelial function was assessed by brachial artery response to reactive hyperemia (flow-mediated dilation, FMD) via ultrasonography. Arterial stiffness was assessed by carotid to femoral pulse wave velocity (cfPWV) via use of the cuff-based SphygmoCor Xcel. Results: Binge drinkers (n=6) had an AUDIT score≥5 (11.8±2.1) and positive phosphatidylethanol level (162±103 ng/mL), while alcohol abstainers (n=6) had an AUDIT score≤1 (0.8±0.2) and negative phosphatidylethanol level. Compared to alcohol abstainers, binge drinkers had a lower brachial artery FMD (alcohol abstainers vs. binge drinkers: 9.8±1.2% vs. 5.1±0.9%, P=0.01), but similar cfPWV (7.2±0.7 vs. 7.0±0.5 m/sec, P=0.8). Conclusions: Our results indicate that compared to mid-life adult alcohol abstainers, binge drinkers had lower endothelial function, but similar arterial stiffness. These findings suggest that repeated binge drinking may further impair endothelial function throughout the aging process.

The Impact of Periodontal Inflammation on Endothelial Function Assessed by Circulating Levels of Asymmetric Dimethylarginine: A Single-Blinded Randomized Clinical Trial.

Background: Endothelial dysfunction is one of the early pathogenic events of the atherosclerotic process. Severe periodontitis is considered to be an independent contributing risk factor for the pathophysiology of endothelial dysfunction. High blood concentration of asymmetric dimethylarginine (ADMA), an L-arginine analogue that inhibits nitric oxide (NO) formation, has emerged as one of the most powerful independent risk predictors of cardiovascular disease. Abrogation of periodontal inflammation might have clinical relevance, affecting the ADMA. Insufficient clinical evidence exists for drawing clear conclusions regarding the long-term effects of periodontal disease on endothelial function, and even less evidence is available specifically on ADMA concentrations and their relationship with periodontitis. The objective of this study was to evaluate the effects of intensive periodontal treatment in modulating the endothelial function via the assessment of plasma ADMA concentration in patients diagnosed severe periodontitis. Methods: This was a 6-month randomized controlled trial, including 140 patients between 41 and 63 years old who were diagnosed with severe periodontitis, free from cardiovascular disease (CVD), and had traditional cardiovascular risk factors. All patients underwent a complete medical and clinical periodontal examination, a laboratory analysis of ADMA, and an ultrasound assessment of FMD of the right brachial artery. After the screening, they were randomly assigned to receive either intensive periodontal treatment (test group, n = 70) or community-based periodontal care (control group, n = 70). A full examination was carried out at baseline, 3 and 6 months after the periodontal treatment. Results: A total of 236 individuals diagnosed with periodontitis were screened. One hundred forty participants were enrolled. No statistically significant difference was observed over the time in ADMA concentration after the intensive periodontal treatment within the test group. No differences were revealed between the groups in the ADMA concentration at baseline and during follow-up. Conclusions: Intensive periodontal treatment does not affect the plasma levels of ADMA in patients without any risk for cardiovascular disease.

FLOW MEDIATED-DILATATION IS ALREADY ABNORMAL IN PRE-IMPAIRED GLUCOSE TOLERANCE (PRE-IGT) AND WITH NO CORRELATION WITH SYSTOLIC BLOOD PRESSURE AND DIASTOLIC BLOOD PRESSURE

Objective: Pre-impaired glucose tolerance (Pre-IGT) is a stage of compensatory hyperinsulinemia to maintain normoglycemia. It is the earliest stage of glucose dysmetabolism, where beta cells can still compensate for the insulin resistance thru hyperinsulinemia. Endothelial dysfunction is a critical part in the pathogenesis of macrovascular and microvascular chronic complications in type 2 diabetes, ordinarily due to uncontrolled hyperglycemia. In pre-IGT the main problem is hyperinsulinemia on a background of normal blood sugar. C-peptide, a segment cleaved off from pro-insulin is equimolar to insulin, and has shown to cause intima media thickening. This study was undertaken to determine endothelial function of patients with pre-IGT thru flow-mediated dilatation of the brachial artery and to correlate the FMD with the insulin level, systolic blood pressure and diastolic blood pressure. Design and method: This is a cross-sectional analytical study of adult patients with risk factors for developing diabetes such as, having first-degree relative with diabetes, obesity, history of gestational diabetes, and polycystic ovary syndrome (PCOS). Systolic and diastolic BP, BMI, 2-hour serum insulin, blood sugar, and lipids were determined. Patients with pre-IGT underwent brachial artery FMD. Results: Of the 27 subjects, 21 (77.8%) had pre-IGT. The mean oral glucose tolerance test at 2-hours post-prandial was normal at 109.53 mg/dL (SD = 30.26). Results of the laboratory tests were as follows: mean Hba1c and insulin at 2 hours were 5.34% (SD = 0.44) and 112.21 uIU/mL (SD = 111.24, normal range 2.60–24.90), respectively. Comparative analyses of the demographic and clinical profiles showed similar characteristics between the normoinsulinemic and the pre-IGT subjects (p &gt; 0.05), although there were more with positive history of type 2 DM and obesity on the latter group. Systolic and diastolic BP levels were normal. Of the 27 subjects, four (4) had abnormal FMD which had a small positive correlation with thee insulin level, systolic BP, and diastolic BP, although not statistically significant (p &gt; 0.05). Conclusions: Endothelial dysfunction has shown to exist already in the pre-IGT subjects depicted in the abnormality in the arterial flow-mediated dilatation study. Systolic BP and diastolic BP levels have not shown any significant correlation with the FMD finding, and the insulin level.

CHA2DS2 VASc score and brachial artery flow-mediated dilation as predictors for no-reflow phenomenon in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention

BackgroundFollowing primary percutaneous coronary intervention (PCI), no-reflow is associated with a high rate of long-term unfavorable clinical outcomes. Despite the importance of early no-reflow prediction in cardiovascular medicine, noninvasive assessment is lacking. This study aimed to evaluate the preprocedural CHA2DS2 VASc score and the brachial artery flow-mediated dilation percentage (FMD%) as predictors of the no-reflow phenomenon in patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing primary PCI.ResultsThis study included 150 patients who presented with acute STEMI, underwent primary PCI, and were divided into two groups according to the flow result, reflow group and a no-reflow group. The CHA2DS2 VASc score was calculated and evaluation of endothelial function by measuring the brachial artery FDM% was done for each patient before the procedure. There were 39 (26%) patients in the no-reflow group and 111 (74%) in the reflow group. The no-reflow patients were older and had significantly higher body mass index (BMI), higher frequency of diabetes mellitus, hypertension, history of heart failure, dyslipidemia, Killip class IV on admission, thrombus grade V, multiple affected vessels, conventional stenting, and multiple stents placement, longer ischemic times, higher CHA2DS VASc score, and lower brachial artery FMD% (p-values of < 0.05 for all). Moreover, there was a significant negative correlation between CHA2DS VAS score and preprocedural FMD%, with the higher the score indicating lower FMD among cases (p-value = 0.000).ConclusionsPreprocedural CHA2DS2 VASc score and the brachial artery FMD can be used as predictors for the no-reflow phenomenon in patients with STEMI, undergoing primary PCI.

Vascular and Cardiac Prognostic Determinants in Patients with Gynecological Cancers: A Six-Year Follow-up Study

Background: The aim of this study was to assess the role of cardiac and vascular parameters as all-cause mortality determinants in patients suffering from gynecological cancers. Methods: This was an observational, prospective, non-randomized, and non-controlled study. Forty-seven consecutive patients (mean age: 58 ± 13 years) were enrolled after cancer staging. All patients underwent evaluation of vascular (common carotid intima-media thickness (mean C-IMT), flow-mediated dilation of the brachial artery (FMD), and antero-posterior diameter of the infrarenal abdominal aorta (APAO)) and cardiac function and morphology before cancer-related interventions. A 6-year follow-up was carried out to assess the overall survival of the whole population. Results: Twenty patients (42%) died by the time of the 6-year follow-up. The brachial artery FMD values were higher in the survivors than the non-survivors (9.71 ± 3.53% vs. 6.13 ± 2.62%, p &lt; 0.001), as well as the LVEF (60.8 ± 3.0% vs. 57.8 ± 4.4%, p = 0.009). There were no differences in the mean C-IMT, APAO, and other echocardiographic parameters. ROC curve analysis identified a baseline LVEF &lt; 57% and FMD value &lt; 5.8% as the best cut-offs. Kaplan–Meier evaluation showed that the LVEF, tricuspid annular plane systolic excursion, and FMD were the best predictors of all-cause mortality, although only the LVEF and FMD were confirmed in multivariate Cox regression analysis. Conclusions: The LVEF and brachial artery FMD are independent prognostic determinants in patients with gynecological cancers.

Acute flywheel exercise does not impair the brachial artery vasodilation in healthy men of varying aerobic fitness.

The cardiovascular response to variable load exercise on a flywheel ergometer is still unknown. This study examined the effects of flywheel exercise on cardiovascular response and brachial artery vasodilation capacity in healthy, active men. In this cross-sectional study, nineteen men (20-57 years old) completed three laboratory visits, including a ramp exercise test to determine their maximal oxygen uptake JOURNAL/blpmo/04.03/00126097-202106000-00008/inline-graphic1/v/2021-04-27T091817Z/r/image-tiff max, and exercise intervention on a flywheel ergometer set at 0.075 kg·m2 moment of inertia. After the ramp test cessation, all participants were allocated into aerobically untrained (n = 10) and trained (n = 9) groups. Throughout the flywheel exercise, cardiovascular demands were continuously monitored via Finapres, while a pre/postflow-mediated dilation (FMD) assessment was performed using ultrasound imaging. There were no differences observed between the groups in their anthropometrics, age or resting brachial artery diameter, while the JOURNAL/blpmo/04.03/00126097-202106000-00008/inline-graphic2/v/2021-04-27T091817Z/r/image-tiff max was ~15% higher (P = 0.001) in trained compared to aerobically untrained group. The cardiovascular response to the flywheel exercise was similar between the groups, with peak mean arterial pressure and heart rate readings reaching ~160 mmHg and ~140 bpm, respectively. The flywheel exercise did not impair the FMD (%) response, which was comparable between the groups (P = 0.256). When these data were pooled, the regression analysis showed an inverse relationship among FMD (%), age (β = -0.936, P = 0.001) and JOURNAL/blpmo/04.03/00126097-202106000-00008/inline-graphic3/v/2021-04-27T091817Z/r/image-tiffmax. (β = -0.359, P = 0.045). Although aerobic fitness alone does not directly explain the FMD response to flywheel exercise, aerobically untrained individuals, as they get older, tend to have lower brachial artery FMD.

Endothelial-protective effects of a G-protein-biased sphingosine-1 phosphate receptor-1 agonist, SAR247799, in type-2 diabetes rats and a randomized placebo-controlled patient trial.

AimsSAR247799 is a G‐protein‐biased sphingosine‐1 phosphate receptor‐1 (S1P1) agonist designed to activate endothelial S1P1 and provide endothelial‐protective properties, while limiting S1P1 desensitization and consequent lymphocyte‐count reduction associated with higher doses. The aim was to show whether S1P1 activation can promote endothelial effects in patients and, if so, select SAR247799 doses for further clinical investigation.MethodsType‐2 diabetes patients, enriched for endothelial dysfunction (flow‐mediated dilation, FMD <7%; n = 54), were randomized, in 2 sequential cohorts, to 28‐day once‐daily treatment with SAR247799 (1 or 5 mg in ascending cohorts), placebo or 50 mg sildenafil (positive control) in a 5:2:2 ratio per cohort. Endothelial function was assessed by brachial artery FMD. Renal function, biomarkers and lymphocytes were measured following 5‐week SAR247799 treatment (3 doses) to Zucker diabetic fatty rats and the data used to select the doses for human testing.ResultsThe maximum FMD change from baseline vs placebo for all treatments was reached on day 35; mean differences vs placebo were 0.60% (95% confidence interval [CI] −0.34 to 1.53%; P = .203) for 1 mg SAR247799, 1.07% (95% CI 0.13 to 2.01%; P = .026) for 5 mg SAR247799 and 0.88% (95% CI −0.15 to 1.91%; P = .093) for 50 mg sildenafil. Both doses of SAR247799 were well tolerated, did not affect blood pressure, and were associated with minimal‐to‐no lymphocyte reduction and small‐to‐moderate heart rate decrease.ConclusionThese data provide the first human evidence suggesting endothelial‐protective properties of S1P1 activation, with SAR247799 being as effective as the clinical benchmark, sildenafil. Further clinical testing of SAR247799, at sub‐lymphocyte‐reducing doses (≤5 mg), is warranted in vascular diseases associated with endothelial dysfunction.

Sacubitril-valsartan improves conduit vessel function and functional capacity and reduces inflammation in heart failure with reduced ejection fraction.

The Prospective comparison of ARNI with angiotensin-converting enzyme inhibitor to Determine Impact on Global Mortality and morbidity in Heart Failure trial identified a marked reduction in the risk of death and hospitalization for heart failure in patients with heart failure with reduced ejection fraction (HFrEF) treated with sacubitril-valsartan (trade name Entresto), but the physiological processes underpinning these improvements are unclear. We tested the hypothesis that treatment with sacubitril-valsartan improves peripheral vascular function, functional capacity, and inflammation in patients with HFrEF. We prospectively studied patients with HFrEF (n = 11, 10 M/1 F, left ventricular ejection fraction = 27 ± 8%) on optimal, guideline-directed medical treatment who were subsequently prescribed sacubitril-valsartan (open-label, uncontrolled, and unblinded). Peripheral vascular function [brachial artery flow-mediated dilation (FMD, conduit vessel function) and reactive hyperemia (RH, microvascular function)], functional capacity [six-minute walk test (6MWT) distance], and the proinflammatory biomarkers tumor necrosis factor-α (TNF-α) and interleukin-18 (IL-18) were obtained at baseline and at 1, 2, and 3 mo of treatment. %FMD improved after 1 mo of treatment, and this favorable response persisted for months 2 and 3 (baseline: 3.25 ± 1.75%; 1 mo: 5.23 ± 2.36%; 2 mo: 5.81 ± 1.79%; 3 mo: 6.35 ± 2.77%), whereas RH remained unchanged. 6MWT distance increased at months 2 and 3 (baseline: 420 ± 92 m; 1 mo: 436 ± 98 m; 2 mo: 465 ± 115 m; 3 mo: 460 ± 110 m), and there was a sustained reduction in TNF-α (baseline: 2.38 ± 1.35 pg/mL; 1 mo: 2.06 ± 1.52 pg/mL; 2 mo: 1.95 ± 1.34 pg/mL; 3 mo: 1.92 ± 1.37 pg/mL) and a reduction in IL-18 at month 3 (baseline: 654 ± 150 pg/mL; 1 mo: 595 ± 140 pg/mL; 2 mo: 601 ± 176 pg/mL; 3 mo: 571 ± 127 pg/mL). This study provides new evidence for the potential of this new drug class to improve conduit vessel function, functional capacity, and inflammation in patients with HFrEF.NEW & NOTEWORTHY We observed an approximately twofold improvement in conduit vessel function (brachial artery FMD), increased functional capacity (6MWT distance), and a reduction in inflammation (TNF-α and IL-18) following 3 mo of sacubitril-valsartan therapy. These findings provide important new information concerning the physiological mechanisms by which this new drug class provokes favorable changes in HFrEF pathophysiology.

Abstract 16510: Acute Use Impairs Vascular Function in Exclusive Juul Users (the Jive Study)

Introduction: The use of pod-based electronic cigarettes such as JUUL has especially increased among youth and young adults. Due to its popularity and high nicotine delivery as salts, JUUL warrants assessment of its cardiovascular effects. Hypothesis: JUUL use alters vascular function. Methods: In the JUUL Impact on Vascular Effects (JIVE) Study, we evaluated endothelial function and blood pressure (BP) in healthy young adults aged 18-40 who were either tobacco nonusers (N=23), exclusive combustible cigarette users (N=17) or exclusive JUUL users (N=15). Results: As shown in the figure, no differences were noted in baseline brachial artery FMD across the 3 groups. Both JUUL and combustible cigarette users had higher systolic and diastolic BP compared to nonusers (P&lt;0.01). Following 10-minute structured use, JUUL decreased FMD more than nonuse (P&lt;0.01) and was similar to combustible cigarette use (P=0.30 vs JUUL). These differences persisted in models adjusted for age, race and sex. Additionally, JUUL use induced an acute rise in systolic BP (6 ± 6mmHg) that differed from nonuse (0.3 ± 5 mmHg, P=0.001) but was similar to combustible cigarette use (8 mmHg, P=1.0). Urinary cotinine and nicotine levels were higher in combustible cigarette and JUUL users following acute exposure (general linear model adjusted for urinary creatinine with overall P&lt;0.01, combustible cigarette vs nonusers P&lt;0.01, JUUL vs nonusers P&lt;0.01). Conclusions: Our results indicate that acute and chronic JUUL use are associated with higher BP, and acute use with a decrease in endothelial function similar to acute combustible cigarette use, thereby suggesting that JUUL alters vascular function both chronically and upon acute exposure in healthy young adults. Further studies are needed to evaluate the long-term impact of JUUL use on vascular health.

Mitochondrial Targeted Antioxidant Intake Improves Vascular Function And Exercise Tolerance In Peripheral Artery Disease Patients

Peripheral artery disease (PAD) is a manifestation of atherosclerosis in the lower leg arteries, which causes reduced blood flow and leg pain. This may be in part due to excessive mitochondria-produced reactive oxygen species (ROS) and attenuated mitochondrial respiratory function. Mitoquinol mesylate, a mitochondrial-targeted antioxidant, has been shown to scavenge ROS and improve vascular function in older adults and animal models. However, the impacts of mitoquinol on vascular function in patients with PAD are unknown. PURPOSE: To examine the impacts of acute mitoquinol intake (80mg) on endothelial function (flow mediated dilation, FMD), resting heart rate (RHR), blood pressure (BP), arterial stiffness (pulse wave velocity, PWV), and exercise tolerance in patients with PAD. METHODS: 10 patients with PAD (stage II-III) received either mitoquinol or placebo in a randomized crossover design. At each visit, measurements of RHR, central and peripheral BP, brachial and popliteal artery FMD, PWV, augmentation index (AIx), maximal walking capacity, and time to claudication (COT) were measured before and after mitoquinol and placebo. RESULTS: There were significant group by time interactions (p<0.05) for brachial FMD, popliteal FMD, and COT, which significantly increased (p<0.05). There were trends for decreases in diastolic BP (p=0.10), carotid-to-ankle PWV (p=0.08), and increases in maximal walking time (p=0.06), and maximal walking distance (p=0.06). There were no changes in RHR, systolic BP, central BP, deceleration time, max dP/dt, carotid-to-radial PWV, carotid-to-femoral PWV, or AIx (p>0.05). CONCLUSIONS: Mitoquinol intake may be an effective strategy for targeting mitochondrial ROS, which may be useful for treating endothelial dysfunction, leg pain, and improving walking time in patients with PAD.

Abstract 071: Endothelin-1 Contributes to Vascular Dysfunction in Peri-Menopausal Women

Declines in vascular function occur early in the menopausal transition, as previously demonstrated by a reduction in endothelial function in perimenopausal women (PERI). However, the mechanisms contributing to this decline remain to be elucidated. We have previously shown that vascular impairments in postmenopausal women (POST) are due in part to endothelin-1 (ET-1). Thus, the purpose of this study is to determine if ET-1 contributes to reductions in vascular function across the stages of the menopausal transition. We hypothesized plasma ET-1 levels would be elevated across menopausal stages, and negatively associated with endothelial function. We further hypothesized that ETB receptors would contribute to impaired vascular function in PERI. Methods: We measured vascular endothelial function (flow-mediated dilation, FMD) and plasma ET-1 in 180 women classified as premenopausal (PRE, n=33, 33±7 years), early PERI (n=20, 50±3 years), late PERI (n=25, 50±4 years), early POST (n=36, 55±3 years), and late POST (n=58, 60±4 years) based on the STRAW criteria. In a separate, secondary study, we measured cutaneous microvascular endothelial function via local heating during microdialysis perfusions of lactated Ringers (control) or ETB receptor antagonist (BQ-788, 300 nM) in 6 PRE (22±2 years) and 8 PERI (50±3 years). Results: Plasma ET-1 concentration increased in a step-wise fashion across menopausal stage (PRE 5.4±1.1, early PERI 5.8±1.0, late PERI 6.1±1.6, early POST 6.4±1.6, late POST 6.4±1.5 pg/mL; P&lt;0.01). Furthermore, there was a significant inverse correlation between plasma ET-1 and brachial artery FMD (r=0.28; P&lt;0.001). In our secondary study, cutaneous microvascular vasodilation was lower in PERI compared to PRE (82±7 vs 92±8 %CVCmax, P &lt;0.05). In PRE, ETB receptor blockade mediated dilation (control: 92±8 vs ETB: 83±9 %CVCmax, P &lt;0.05), however this effect was lost in PERI (82±7 vs 92±4 %CVCmax, P &lt;0.05). Conclusions: These data suggest that elevated ET-1 contributes to impairments in vascular endothelial function across the menopausal transition. Furthermore, the decline in endothelial function is evident in the macro- and micro- circulation during the perimenopausal transition, due in part to a loss of ETB mediated dilation.