Brachial Flow-mediated Dilation Research Articles

Brain atrophy, reduced cerebral perfusion, arterial stiffening, and wall thickening with aging coincide with stimulus-specific changes in fMRI-BOLD responses.

The aim of this study was to investigate how aging affects blood flow and structure of the brain. It was hypothesized older individuals would have lower gray matter volume (GMV), resting cerebral blood flow (CBF0), and depressed responses to isometabolic and neurometabolic stimuli. In addition, increased carotid-femoral pulse-wave velocity (PWV), carotid intima-media thickness (IMT), and decreased brachial flow-mediated dilation (FMD) would be associated with lower CBF0, cerebrovascular reactivity (CVR), and GMV. Brain scans (magnetic resonance imaging) and cardiovascular examinations were conducted in young (age = 24 ± 3 yr, range = 22-28 yr; n = 13) and old (age = 71 ± 4 yr; range = 67-82 yr, n = 14) participants, and CBF0, CVR [isometabolic % blood oxygen level-dependent (BOLD) in response to a breath hold (BH)], brain activation patterns during a working memory task (neurometabolic %BOLD response to N-back trial), GMV, PWV, IMT, and FMD were measured. CBF0 and to a lesser extent CVRBH were lower in the old group (P ≤ 0.050); however, the increase in the %BOLD response to the memory task was not blunted (P ≥ 0.2867). Age-related differential activation patterns during the working memory task were characterized by disinhibition of the default mode network in the old group (P < 0.0001). Linear regression analyses revealed PWV, and IMT were negatively correlated with CBF0, CVRBH, and GMV across age groups, but within the old group alone only the relationships between PWV-CVRBH and IMT-GMV remained significant (P ≤ 0.0183). These findings suggest the impacts of age on cerebral %BOLD responses are stimulus specific, brain aging involves alterations in cerebrovascular and possibly neurocognitive control, and arterial stiffening and wall thickening may serve a role in cerebrovascular aging.NEW & NOTEWORTHY Cerebral perfusion was lower in old versus young adults. %Blood oxygen level-dependent (BOLD) responses to an isometabolic stimulus and gray matter volume were decreased in old versus young adults and associated with arterial stiffening and wall thickening. The increased %BOLD response to a neurometabolic stimulus appeared unaffected by age; however, the old group displayed disinhibition of the default mode network during the stimulus. Thus, age-related alterations in cerebral %BOLD responses were stimulus specific and related to arterial remodeling.

Impact of heat-not-burn cigarette passive smoking on children's oxidative stress, endothelial and platelet function

Growing global use of heat-not-burn cigarettes (HNBC) prompts investigation. Prior studies assessed HNBC's effects on cardiovascular health, revealing heightened oxidative stress, platelet activation, and endothelial dysfunction. However, limited understanding exists regarding passive smoking's impact on children exposed to HNBC.This study aims to assess levels of oxidative stress, endothelial and platelet function among children exposed to passive smoke from HNBC, traditional tobacco (TT) cigarettes and unexposed subjects.Seventy-eight children (2–18 years) were divided into three groups: HNBC passive smokers (n = 26), TT cigarette exposed (n = 26), and control (CNT) group (n = 26, unexposed).Oxidative stress was evaluated by serum NADPH oxidase-2 (NOX2) activity, assessed by soluble Nox2-derived peptide (sNOX2-dp), isoprostanes, hydrogen peroxide (H2O2) production, hydrogen break-down activity (HBA) and NO bioavailability. Endothelial function was assessed by brachial flow-mediated dilation (FMD). Platelet function was evaluated by soluble CD40 ligand (sCD40L), soluble P-selectin (sP-selectin) and thrombus formation by T-TAS analysis.Passive smoking-exposed children (both HNBC and TT) exhibited significantly increased serum sNOX2-dp, isoprostanes, H2O2, sCD40L sP-selectin and thrombus formation versus controls. Conversely, exposed children displayed reduced brachial FMD and serum NO bioavailability. No significant differences were found between children exposed to passive smoking of HNBC vs TT.Multivariable regression linked sNOX2 (standardized coefficient β: 0.284; SE: 0.040; p = 0.01) and H2O2 (standardized coefficient β: 0.243; SE: 0.0; p = 0.02) as independent predictors of FMD, and isoprostanes (standardized coefficient β:0.388; SE: 0.022; p < 0.001) and serum cotinine (standardized coefficient β:0.270; SE: 0.048; p = 0.01) with sNOX2-dp levels.Exposure to HNBC smoke heightened oxidative stress, endothelial dysfunction, platelet activation, and thrombus formation in children. Findings suggest avenues for interventions to curb childhood passive smoking exposure.

Impaired brachial flow-mediated dilation may predict choroidal and retinal nerve fibre layer thickness changes in people with obesity

ABSTRACT Clinical relevance Choroidal thickness and peripapillary retinal nerve fibre layer (RNFL) changes are known to occur in obesity. Endothelial dysfunction and systemic atherosclerosis may play a role in the pathophysiology of these differences. Background Flow-mediated dilation (FMD) is reduced in patients with endothelial dysfunction, and the ankle-brachial index is a surrogate marker for atherosclerosis. This study was conducted to examine the relationship between systemic vascular parameters (FMD, and ankle-brachial index), subfoveal choroidal thickness, and peripapillary RNFL thickness in obese individuals. Methods This observational, cross-sectional study involved 108 total participants who were divided into two groups. One group consisted of 54 obese subjects who each had a body mass index of 30 kg/m2 or more. The other control group contained 54 participants who each had a body mass index of 25 kg/m2 or less but higher than 20 kg/m2 . For each participant, only one eye was examined in this study. Subfoveal choroidal thickness, RNFL thickness, ankle-brachial index, and ultrasound measurement of the brachial artery FMD were performed. FMD was categorised according to receiver operating characteristic analysis, and endothelial dysfunction was defined as an FMD ≤ 7.29%. Results Subfoveal choroidal and RNFL thicknesses in the temporal quadrant were significantly lower in the obese group (p < 0.05). Lower mean values of subfoveal choroidal and RNFL thicknesses in the temporal and inferior quadrants were observed in subjects with an FMD ≤ 7.29% (p < 0.05). In people with obesity, FMD was positively correlated with subfoveal choroidal thickness (r = 0.322, p = 0.001), inferior RNFL thickness (r = 0.259, p = 0.007), and temporal RNFL thickness (r = 0.297, p = 0.002). However, the ankle-brachial index was not correlated with obesity. Conclusions Impaired FMD was associated with reduced subfoveal choroidal and RNFL thicknesses in the temporal and inferior quadrants of people with obesity.

Brachial artery FMD and carotid artery IMT in glaucoma

Aims/Purpose: The purpose of the study was to assess the ultrasound measurements of the brachial artery flow‐mediated dilation (FMD) and carotid artery intima‐media thickness (IMT) and their relationship in glaucoma patients.Methods: Thirty‐seven patients with glaucoma and thirty‐one healthy controls were included in the study. All glaucoma patients and controls underwent ultrasound measurement of FMD of the brachial artery and ultrasound measurement of IMT of the carotid artery.Results: The mean values of brachial FMD were significantly lower among the glaucoma compared with controls (15.3 ± 9.5% vs 19.8 ± 9.3%, p = 0.04). No significant difference was found in carotid IMT (1.2 ± 0.4 vs. 1.1 ± 0.3, p = 0.4), and brachial artery diameter at rest (4.7 ± 0.6 vs. 4.9 ± 0.3, p = 0.2) between the glaucoma patients and controls. The significant difference in brachial artery diameter in hyperemia between the glaucoma patients and controls (5.4 ± 0.6 vs. 5.9 ± 0.4, p = 0.002) was found. A negative correlation among brachial FMD and carotid IMT as well as among brachial FMD and brachial artery diameter at rest was found.Conclusions: Impaired brachial FMD indicates presence of systemic vascular endothelial dysfunction in glaucoma; glaucoma patients with lower values of the brachial FMD are at increased risk of having thickened carotid IMT.

High-density lipoprotein cholesterol subfraction HDL2 is associated with improved endothelial function in systemic lupus erythematosus.

Patients with systemic lupus erythematosus (SLE) have increased risk of premature atherosclerosis but the exact mechanisms remains unclear. Flow-mediated dilatation (FMD) is an established non-invasive assessment of vascular endothelial function. Lipoprotein subfractions may be better predictors of FMD than conventional cholesterol measurements. We tested the hypothesis that lipoprotein subfractions are independently associated with FMD. Forty-one consecutive adult patients with SLE without known cardiovascular risk factors or disease were recruited in this cross-sectional study. Endothelial function and early atherosclerosis were assessed by brachial FMD and common carotid artery (CCA) intima-media thickness (IMT). High-density lipoprotein (HDL)/low-density lipoprotein (LDL) subfractions were measured. Machine learning models were also constructed to predict FMD and CCA IMT. Median FMD was 4.48% (IQR 5.00%) while median IMT was 0.54 mm (IQR 0.12 mm). Univariate analysis showed lower LDL1 (r=-0.313, p<0.05) and higher HDL2 subfractions (r=0.313, p<0.05) were significantly associated with higher log-transformed FMD. In a multiple linear regression model, HDL2 (β=0.024, SE=0.012, p<0.05) remained an independent predictor of higher FMD after adjusting for age, body mass index, LDL1 and systolic blood pressure. The machine learning model included parameters such as HDL2 (positive association), prednisolone dose, LDL cholesterol and LDL1 for prediction of FMD (r=0.433, p<0.01). Age, LDL cholesterol and systolic blood pressure were independently associated with higher CCA IMT after adjusting for body mass index and HDL2. HDL 2, a large HDL particle, was independently associated with greater FMD and may be a biomarker of vascular health in SLE.

Association of number of siblings with preclinical markers of cardiovascular disease. The cardiovascular risk in Young Finns study

To investigate the association of number of siblings with preclinical cardiovascular disease (CVD) markers in adulthood.The sample comprised 2776 participants (54 % female) from the Cardiovascular Risk in Young Finns Study who had CVD risk factor data measured in childhood in 1980 (aged 3–18 years) and markers of preclinical CVD measured in adulthood. Echocardiography was performed in 2011, and carotid intima-media thickness, carotid distensibility, brachial flow-mediated dilatation, and arterial pulse wave velocity were measured in 2001 or 2007. The association between the number of siblings and preclinical CVD was assessed using generalized linear and logistic regression models. Analyses were stratified by sex as associations differed between sexes.Women with 1 sibling had lower E/e’-ratio (4.9, [95%CI 4.8–5.0]) in echocardiography compared with those without siblings (5.1[4.9–5.2]) and those with ≥2 more siblings (5.1[5.0–5.2]) (P for trend 0.01). Men without siblings had the lowest E/A-ratio (1.4[1.3–1.5]) compared with those with 1 sibling (1.5[1.5–1.5]), or ≥2 siblings (1.5[1.5–1.5]) (P for trend 0.01). Women without siblings had highest left ventricular ejection fraction (59.2 %[58.6–59.7 %]) compared with those with 1 sibling (59.1 %[58.8–59.4 %]), or ≥2 siblings (58.4 %[58.1–58.8 %])(P for trend 0.01). In women, brachial flow-mediated dilatation, a measure of endothelial function, was the lowest among participants with ≥2 siblings (9.4 %[9.0–9.8 %]) compared with those with 1 sibling (10.0 %[9.6–10.3 %]) and those without siblings (10.4 %[9.7–11.0 %])(P for trend 0.03).We observed that number of siblings may be associated with increased risk of heart failure in women. As the associations were somewhat inconsistent in males and females, further research is warranted.

Fat intake impairs the recovery of endothelial function following mental stress in young healthy adults.

Mental stress has been identified as a trigger of cardiovascular events. A single episode of stress can induce acute impairments in endothelial function in healthy adults. Importantly, during stressful periods, individuals often resort to unhealthy behaviors, such as increased consumption of high-fat foods, which is also known to negatively impact endothelial function. Therefore, this study examined whether consumption of a high-fat meal would further exacerbate the negative effect of mental stress on vascular function. In a randomized, counterbalanced, cross- over, postprandial intervention study, 21 healthy males and females ingested a high-fat (56.5 g fat) or a low-fat (11.4 g fat) meal 1.5 h before an 8-min mental stress task (Paced-Auditory-Serial-Addition-Task, PASAT). Plasma triglyceride (TAG) concentration was assessed pre-and post-meal. Forearm blood flow (FBF), blood pressure (BP), and cardiovascular activity were assessed pre-meal at rest and post-meal at rest and during stress. Endothelial function, measured by brachial flow-mediated dilatation (FMD) was assessed pre-meal and 30 and 90 min following mental stress. Plasma TAG concentration was significantly increased following the high-fat meal compared to the low-fat condition. Mental stress induced similar increases in peripheral vasodilation, BP, and cardiovascular activity, and impaired FMD 30 min post-stress, in both conditions. FMD remained significantly impaired 90 min following stress in the high-fat condition only, suggesting that consumption of fat attenuates the recovery of endothelial function following mental stress. Given the prevalence of fat consumption during stressful periods among young adults, these findings have important implications for dietary choices to protect the vasculature during periods of stress.

Vascular effects and benefits through Helical stent implantation vs. conventional stenting: Methodology and initial Results of The MIMICS FLOW investigator-initiated randomized controlled trial

Abstract Aims Endovascular treatment is the primary revascularization strategy for symptomatic peripheral artery disease (PAD), which not only restores tissue perfusion but also affects local lower limb arterial endothelial function. Endothelial dysfunction is the pathophysiologic principle involved in the progression of atherosclerosis and is a prognostically relevant cardiovascular biomarker. A helical stent with a unique 3D helical geometry promotes laminar swirling blood flow elevating wall sheer stress, providing superior hemodynamic advantages and excellent clinical performance as compared to conventional stenting. The potential impact on endothelial homeostasis and the detailed mechanisms following a biomimetic or conventional stent are unknown. To this aim we now determined the effect of the Biomimics or a conventional stent on endothelial and vascular function in symptomatic PAD. Methods The MIMICS-FLOW is an investigator-initiated single-blind, randomized controlled trial (NCT05447052). The influence of novel stent-platforms with improved hemodynamic capabilities with respect to vasomotion of the vessel wall, vascular function and vascular compliance was measured by flow-mediated dilation (FMD) and arterial stiffness indices. Vascular function was determined in 70 PAD patients, Rutherford 2, 3 and 4 randomized to a helical stent and the conventional straight nitinol stent before and after lower limb intervention with a one-month follow-up in the nonstenotic segment of the proximal SFA. Perfusion indices, TLR rate and primary patency were assessed. Results The methodology and initial results regarding endothelial function after 1 month will be presented at ESC. In brief, 70 Patients aged 67 years were 1:1 randomized to each group prior to stent implantation in the SFA. Rutherford and PACSS class and target lesion locations were balanced between groups. One patient in the helical and 2 patients in the Straight group required a reintervention. A higher improvement in SFA FMD was observed in the helical group as compared to conventional stenting (p&amp;lt;0.05). Importantly, this effect was mirrored also by a greater increase in brachial FMD in the helical vs. conventional group (p&amp;lt;0.05). No impact was observed between groups regarding arterial or aortic stiffness. Conclusions Our RCT data provide evidence for an improved vascular function through swirling flow with superior hemodynamics following a helical stent implantation. These findings support the concept for a better mechanistic understanding to enhance endovascular treatment strategies in PAD.

Impaired cardiorespiratory fitness and endothelial function after SARS-CoV-2 infection in a sample of mainly immunocompromised youth.

This study aimed to compare cardiopulmonary fitness and endothelial function 6 months after hospital diagnosis in a sample mainly comprising immunocompromised patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection versus noninfected controls. Youth (n = 30; age: 14 yr; 60% females) with confirmed SARS-CoV-2 seen in a tertiary hospital of Sao Paulo, Brazil, were matched by propensity score based on BMI, age, sex, and pre-existing diseases with a control group who had not been tested positive for SARS-CoV-2 infection (n = 30; age: 15 yr; 50% females). Cardiopulmonary fitness (by means of a cardiopulmonary exercise test: CPET) and brachial flow-mediated dilation (%b-FMD) were assessed 3-6 mo after diagnosis. Patients were matched by propensity score based on BMI, age, sex and pre-existing diseases, if any, with a control group who had not been tested positive for SARS-CoV-2. Compared with controls, patients with COVID-19 showed reduced ventilatory anaerobic threshold (VAT) and peak exercise time and minute ventilation/maximum voluntary ventilation (V̇e/MVV) (all P < 0.01). Brachial endothelial function variables were all adjusted for body surface area (BSA). Patients with COVID-19 had decreased %b-FMD (3.6 vs. 5.4; P = 0.03) mean and positive flow (P = 0.02 and P = 0.03, respectively) versus controls. Adjusted linear regression models exploring associations between CPET variables, %b-FMD and the potential predictors post-COVID-19 syndrome, number of symptoms, hospitalization, and COVID severity did not detect significant associations, except for total shear rate in hospitalization (coefficient: -65.07 [95%CI -119.5;-10.5], P = 0.02). Immunocompromised and previously healthy children and adolescents with COVID-19 presented with impaired exercise capacity and endothelial dysfunction when compared with their noninfected counterparts, but the mechanisms remain unknown.NEW & NOTEWORTHY COVID-19 appeared to impair recovery of exercise capacity and endothelial function in a sample mainly comprising immunocompromised patients, but the mechanisms are unknown. These findings support the need for preventive measures against COVID-19 in this vulnerable population and suggest the necessity of proper monitoring and treatment for these patients.

Effect of Yoga on Endothelial Function: A Systematic Review and Meta-Analysis.

Introduction: Endothelial dysfunction is the initial step in the pathogenesis of atherosclerosis; and it plays a central role in the development of cardiovascular diseases and many types of human diseases (diabetes, kidney failure, cancer, and viral infections). Strategies that are effective in protecting vascular endothelial function and retard or reversing endothelial dysfunction in the early stage appear to be potential in the prevention of vascular, cardiac, and many human diseases. Several studies have been carried out on the effects of yoga on endothelial function, but the results of these studies have not been synthesized. This study aimed at conducting a systematic review and meta-analysis to determine the effectiveness of yoga on endothelial function. Methods: A systematic review and meta-analysis of studies that assessed the effect of yoga practice on vascular endothelial function was done as per the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The PubMed, Scopus, Google Scholar, and Cochrane controlled register of trials (CENTRAL) were searched from inception to August 2022. The search strategy was constructed around yoga-based techniques and endothelial function. All the yoga-based interventional studies on endothelial function or dysfunction were included in this review. A narrative synthesis and descriptive analysis were done due to the diverse methodology of selected studies. We carried out a formal meta-analysis of controlled trials that assessed the effect of yoga on flow-mediated dilatation (FMD), a measure of endothelial function. Results: A total of 18 studies were included for review involving 1043 participants. Yoga training showed improved endothelial function in 12 studies, whereas 6 studies did not find any statistically robust effect. Meta-analysis (n = 395 participants, 6-studies, 7 comparisons) showed an increase in brachial FMD by yoga practice (mean difference = -1.23%; 95% confidence interval -2.23 to -0.23; p = 0.02). The heterogeneity between the studies was 43% (Tau2 = 0.70, χ2 = 10.49). The risk of bias was low to moderate in these studies. No adverse effects were reported. Conclusions: Yoga practice improved endothelial function. Yoga could be a safe and potential integrative medicine to improve endothelial function. However, as the statistical heterogeneity, that is, variation in the FMD among the studies was moderate, large clinical trials are necessary for its clinical recommendations.

Prevalence and Determinants of Endothelial Dysfunction among Adults Living with HIV in Northwest Nigeria.

Endothelial dysfunction constitutes an early pathophysiological event in atherogenesis and cardiovascular disease. This study aimed to assess the prevalence, determinants, and degree of endothelial dysfunction in antiretroviral therapy (ART)-treated people living with HIV (PLWH) in northwestern Nigeria using brachial flow-mediated dilatation (FMD). This was a comparative, cross-sectional study. A total of 200 ART-treated adults living with HIV with no evidence of kidney disease were compared with 200 HIV-negative participants attending a tertiary hospital in Kano, Nigeria, between September 2020 and May 2021. Endothelial function was evaluated by measuring FMD with a high-resolution vascular ultrasound transducer. FMD was calculated as the ratio of the brachial artery diameter after reactive hyperemia to baseline diameter and expressed as a percentage of change. Blood and urine samples were obtained from participants in both arms. Urine albumin-to-creatinine ratio (uACR) was calculated using the 2021 CKD-EPI estimated glomerular filtration rate (eGFR) creatinine-cystatin C equation without the race variable, and low-density lipoprotein (LDL) cholesterol was measured using enzymatic method. The overall mean age (± standard deviation) of the study participants was 42 ± 11 years. Participants in the comparison arm were younger than PLWH (38 ± 11 versus 46 ± 10 years, respectively). The median (interquartile range) uACR was 41.6 (23.2-162.9) mg/g for the ART-treated PLWH versus 14.5 (7.4-27.0) mg/g for healthy controls. PLWH had a significantly lower mean percent FMD when compared to HIV-negative participants (9.8% ± 5.4 versus 12.1% ± 9.2, respectively). Reduced FMD was independently associated with HIV infection (β = -2.83%, 95% CI, -4.44% to -1.21%, p = 0.001), estimated glomerular filtration rate (β = -0.04%, 95% CI, -0.07% to -0.01%, p = 0.004) and LDL cholesterol (β = -1.12%, 95% CI, -2.13% to -0.11%, p = 0.029). HIV-positive status, lower estimated GFR, and higher LDL cholesterol levels were independently associated with endothelial dysfunction. Future prospective studies with larger cohorts of persons living with HIV (and age- and sex-matched HIV-negative controls) are needed to gain further insight into these important findings. In the interim, aggressive management of modifiable risk factors is warranted.

Correlation Between Monocyte to High-Density Lipoprotein Cholesterol Ratio, Blood Flow-Mediated Dilation, and Arteriosclerosis in Young and Middle-Aged Patients With Essential Hypertension

Abstract OBJECTIVE To investigate the relationship between monocyte to high-density lipoprotein cholesterol ratio (MHR), flow-mediated dilation (FMD), and arteriosclerosis in young and middle-aged patients with essential hypertension (EH). METHODS A total of 188 young and middle-aged patients with EH admitted to the Department of Cardiovascular Medicine of the First Affiliated Hospital of Anhui Medical University from August 2020 to August 2022 were enrolled. The clinical data, laboratory results, and brachial ankle pulse wave velocity (baPWV) and FMD of all patients were collected. According to baPWV, patients were divided into non-arteriosclerosis group (baPWV &amp;lt;1,400 cm/s, n = 43), mild arteriosclerosis group (baPWV 1,400 to &amp;lt;1,700 cm/s, n = 100), and moderate to severe atherosclerosis group (baPWV 1,700 to &amp;lt;2,000 cm/s, baPWV ≥2,000 cm/s, n = 45). The differences of body mass index, fasting blood glucose, blood lipid, FMD, MHR, hypersensitive C-reactive protein (hsCRP), systolic blood pressure, diastolic blood pressure, monocyte, and other indicators were compared. Spearman correlation analysis was used to analyze the correlation between all variables and baPWV. Multivariate logistic regression analysis was used to analyze the influencing factors of arteriosclerosis in young and middle-aged patients with EH. RESULTS MHR of non-atherosclerosis, mild, and moderate to severe atherosclerosis groups were 0.29 (0.22–0.42), 0.36 (0.27–0.49), and 0.52 (0.43–0.62) 109/mmol, respectively. The difference was statistically significant (H = 33.803, P &amp;lt; 0.05). The FMD of non-atherosclerosis, mild, and moderate to severe atherosclerosis groups were (6.0 ± 1.9)%, (4.9 ± 1.6)%, and (3.5 ± 1.8)%, respectively. The difference was statistically significant (F = 24.239, P &amp;lt; 0.05). Spearman correlation analysis showed that MHR was positively correlated with baPWV (r = 0.39, P &amp;lt; 0.001), and FMD was negatively correlated with baPWV (r = −0.47, P &amp;lt; 0.001). Multivariate logistic regression analysis showed that MHR, FMD, systolic blood pressure, and age were independent influencing factors for arteriosclerosis in in young and middle-aged EH patients, odds ratio (95% CI) was 45.874 (2.140–983.243), 0.763 (0.587–0.991), 1.068 (1.016–1.123), and 1.075 (1.038–1.113), respectively; all P &amp;lt; 0.05. CONCLUSIONS MHR is positively correlated with the occurrence of arteriosclerosis in young and middle-aged patients with EH, and FMD is negatively correlated with the occurrence of arteriosclerosis, and both are independent influencing factors for arteriosclerosis.

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.

The incidence of subclinical atherosclerosis in subjects with low and moderate cardiovascular risk.

The cardiovascular risk models and subclinical atherosclerotic indicators are both recommended for cardiovascular risk stratification. The accordance between the incidence of subclinical atherosclerosis and subjects with low and moderate cardiovascular risk is unclear. Subjects with low and moderate cardiovascular risk have a lower incidence of subclinical atherosclerosis compared with subjects with high risk. Brachial-ankle pulse wave velocity (BaPWV) and brachial flow-mediated dilation (BFMD) were measured in 421 subjects without a history of atherosclerotic cardiovascular disease (ASCVD) from October 2016 to January 2020. All subjects were classified into low, moderate, and high risk based on Framingham and China-par risk models respectively. Mean age was 57.05 ± 9.35 years and 248 (58.9%) were male. In subjects with low, moderate, and high risk assessed by Framingham and China-par risk models, the percentage of abnormal BaPWV ( > 1400 cm/s) was 42.9%, 70.1%, 85.7%, and 40.4%, 71.4%, 89.7%, respectively. Meanwhile, the percentage of abnormal BFMD ( ≤ 7%) was 43.8%, 68.5%, 77.3%, and 44.9%,72.1%, and 76.6%. According to Framingham-based high-risk categories, positive predictive value (PPV), negative predictive value (NPV), sensitivity and specificity for BaPWV abnormality were 85.7%, 39.4%, 36.1%, and 87.5%, respectively. For BFMD abnormality, the values were 77.3%, 40.1%, 34.1%, and 81.8%, respectively. According to China-par high-risk categories, the values for BaPWV abnormality were 89.7%, 43.8%, 45.6%, and 89.0%, respectively. For BFMD abnormality, the values were 76.6%, 41.3%, 40.7%, and 77%, respectively. In multivariate analysis, age and blood pressure were the independent predictors for subclinical atherosclerosis in subjects with low-moderate risk. More than one-half of subjects with low and moderate risk already have detectable subclinical atherosclerosis, indicating higher cardiovascular risk beyond the traditional stratification.

Normalization of Flow-mediated Dilation to Brachial Artery Material Property: A Feasibility Study.

Endothelial reactivity (ER) is widely measured using flow-mediated dilation (FMD) of brachial artery. Conventional measurement of FMD is influenced by factors such as input shear stress, arterial transmural pressure, diameter and thereby arterial material properties (ε). Thus, for a reliable interpretation of FMD, it has to be normalized with respect to the above confounding factors. Normalization of FMD with shear stress at the time of measurement has been reported to reduce measurement variability. However, its widespread usage among the research community is limited. In this work, we examine the feasibility of normalizing the brachial FMD index (FMD%) to ε : extrema (εp), baseline (εb) and extrema change (∆ε) post-ischemia using its inter-day variability against FMD. In-vivo measurements were performed on 10 participants for 2 consecutive days and simultaneous pressure-diameter cycles were collected to estimate the material properties during reactive hyperemia (RH). The box-whisker plot reveals differences in the mean and deviation of FMD to FMD|εb. A significant value for repeatability (ICC ≥ 0.6) was obtained for normalized FMD (FMD|εb) for specific stiffness index (β), pressure-strain elastic modulus (Ep), and local pulse wave velocity (PWV) as compared to FMD. Hence, normalization of FMD% to arterial ε can potentially improve the measurement reliability of ER assessment.Clinical Relevance- This pilot study demonstrates the feasibility of brachial artery stiffness assessment during FMD and its potential use for normalizing the standard FMD measurement.

Skipping breakfast does not accelerate the hyperglycemia-induced endothelial dysfunction but reduces blood flow of the brachial artery in young men.

Postprandial hyperglycemia is assumed to have a negative impact on flow-mediated dilation (FMD), an index of endothelial function, and blood flow of the peripheral conduit arteries. This study aimed to determine whether the enhancement of postprandial hyperglycemia by skipping breakfast accelerates endothelial dysfunction and reduces the blood flow in the brachial artery in young men. Using a randomized cross-over design, ten healthy men completed two trials: with and without breakfast (Eating and Fasting trials, respectively). Venous blood sampling and brachial FMD tests were conducted before, 30, 60, 90, and 120min after a 75-g oral glucose tolerance test (OGTT). Skipping breakfast boosted post-OGTT glucose levels than having breakfast (P = 0.01). The magnitude of the decrease in FMD via OGTT did not vary between trials (main effect of trial P = 0.55). Although brachial blood flow tended to decrease after OGTT in both trials (interaction and main effect of time P = 0.61 and P = 0.054, respectively), the decrease in blood flow following OGTT was greater in the Fasting trial than in the Eating trial (main effect of trial, mean difference = -15.8mL/min [95%CI = -25.6 to -6.0mL/min], P < 0.01). Skipping breakfast did not enhance the magnitude of the decrease in FMD following glucose loading, but did accelerate hyperglycemia-induced reduction in brachial blood flow. Current findings suggest that even missing one breakfast has negative impacts on the blood flow regulation of the peripheral conduit arteries in young men who habitually eat breakfast.

#3145 ASSOCIATION OF ENDOTHELIAL NITRIC OXIDE SYNTHASE GENE POLYMORPHISM WITH ENDOTHELIAL DYSFUNCTION IN DIABETIC NEPHROPATHY AMONG AZERBAIJANIS

Abstract Background and Aims Vascular endothelial dysfunction resulting from impaired nitric oxide synthase (NOS) activity in the endothelial cells of blood vessels has been suggested as playing an important role in the pathogenesis of Diabetic nephropathy (DN). It regulates endothelial function and maintains endothelial-dependent vasodilation in multiple organs, including the kidney. The study was carried out to investigate the association of T-786C single nucleotide polymorphisms with the flow mediated dilation (FMD) in DN among type 2 diabetic subjects. Method 90 patients (45 male and 45 female) with diabetic nephropathy were recruited from Nephrology and Endocrinology departments of the Azerbaijan Medical University hospital. As a control group the results were compared with the findings in 100 healthy Azerbaijani individuals (50 males and 50 females). The study was approved by ethics committee and informed consent was obtained from all patients in written form. Brachial endothelial function was determined by brachial artery vasodilator response or brachial FMD in the dominant arm according to previously validated techniques. T786C polymorphism was detected using polymerase chain reaction-restriction fragment length polymorphism analysis. Results The results showed significant differences between DN group and control group regarding the genotype and allele distributions of the T786C single nucleotide polymorphisms. The CC genotype was significantly more frequent in diabetics nephropathy patients than in control group (42% vs. 8%, p = 0.01). FMD in allele homozygote T786C(TT), T786C(CC) and heterozygote T786C(CT) were respectively 13.5 ±0.16%, 12.3±0.19%,13.9 ±0,28%. In the study groups, Azerbaijani patients showed dominance of the C allele and a mutant homozygous genotype CC of the T786C gene of eNOS. Subjects with the 786C(CC) (n = 48) showed significantly reduced FMD with those with T786C (TT) (n = 7) (p = 0.021) and T786C (CT) (n = 35) (p = 0.023), whereas there was no significant difference in endothelial-independent vasodilation between these groups. Although subjects with homozygote T786C(TT), did not show significantly reduced levels of FMD. Who were carriers of the T786C allele demonstrated markedly reduced levels of FMD compared with noncarriers (p = 0.019). Conclusion The data suggest that in diabetic nephropathy, the eNOS T786C allele may be involved in endothelial dysfunction. Azerbaijani patients showed dominance of the C allele and a mutant homozygous genotype CC of the T786C gene of eNOS.

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

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

Nordic Walking in Water on Cerebrovascular Reactivity and Cognitive Function in Elderly Patients with Type 2 Diabetes.

Aquatic Nordic walking (ANW) is a novel whole-body low-impact exercise that can be practiced by a variety of older adults with chronic conditions. However, its efficacy on several aspects of health is largely unknown. This study aimed to determine the effects of regular ANW on glycemic control and vascular function in older adults with type 2 diabetes and mild cognitive impairment. Thirty-three older adults with type 2 diabetes age 60-75 yr were randomly allocated to nonexercising control ( n = 17) or ANW ( n = 17) groups. Nordic walking was performed in a pool at water temperature of 34°C-36°C, three times per week for 12 wk. Measures of functional physical fitness including chair stand, timed up and go, chair sit and reach, reach and back scratch, and 6-min walk test scores were all improved after ANW (all P < 0.05). Plasma glucose, glycosylated hemoglobin, and homeostasis model assessment of insulin resistance decreased (all P < 0.05) in ANW. Vascular reactivity as assessed by brachial flow-mediated dilation increased, and arterial stiffness as assessed by brachial-ankle pulse wave velocity decreased in ANW (all P < 0.05). No significant changes were observed in the control group. Middle cerebral artery pulsatility index decreased with ANW under normocapnia condition ( P < 0.05). Cerebrovascular conductance increased with ANW under hypercapnia condition. Montreal Cognitive Assessment score increased in the ANW group ( P < 0.001). Changes in Montreal Cognitive Assessment scores were positively associated with corresponding changes in brain-derived neurotrophic factor ( r = 0.540, P = 0.031). Nordic walking in water was a safe and effective innovative exercise modality to improve glycemic control, vascular function, physical fitness, cerebrovascular reactivity, and cognitive function in older adults with type 2 diabetes.

Effect of modernized collaborative care for depression on depressive symptoms and cardiovascular disease risk biomarkers: eIMPACT randomized controlled trial

Although depression is a risk and prognostic factor for cardiovascular disease (CVD), clinical trials treating depression in patients with CVD have not demonstrated cardiovascular benefits. We proposed a novel explanation for the null results for CVD-related outcomes: the late timing of depression treatment in the natural history of CVD. Our objective was to determine whether successful depression treatment before, versus after, clinical CVD onset reduces CVD risk in depression. We conducted a single-center, parallel-group, assessor-blinded randomized controlled trial. Primary care patients with depression and elevated CVD risk from a safety net healthcare system (N = 216, Mage = 59 years, 78% female, 50% Black, 46% with income <$10,000/year) were randomized to 12 months of the eIMPACT intervention (modernized collaborative care involving internet cognitive-behavioral therapy [CBT], telephonic CBT, and/or select antidepressants) or usual primary care for depression (primary care providers supported by embedded behavioral health clinicians and psychiatrists). Outcomes were depressive symptoms and CVD risk biomarkers at 12 months. Intervention participants, versus usual care participants, exhibited moderate-to-large (Hedges’ g = -0.65, p < 0.01) improvements in depressive symptoms. Clinical response data yielded similar results – 43% of intervention participants, versus 17% of usual care participants, had a ≥ 50% reduction in depressive symptoms (OR = 3.73, 95% CI: 1.93–7.21, p < 0.01). However, no treatment group differences were observed for the CVD risk biomarkers – i.e., brachial flow-mediated dilation, high-frequency heart rate variability, interleukin-6, high-sensitivity C-reactive protein, β-thromboglobulin, and platelet factor 4 (Hedges’ gs = -0.23 to 0.02, ps ≥ 0.09). Our modernized collaborative care intervention – which harnessed technology to maximize access and minimize resources – produced clinically meaningful improvements in depressive symptoms. However, successful depression treatment did not lower CVD risk biomarkers. Our findings indicate that depression treatment alone may not be sufficient to reduce the excess CVD risk of people with depression and that alternative approaches are needed. In addition, our effective intervention highlights the utility of eHealth interventions and centralized, remote treatment delivery in safety net clinical settings and could inform contemporary integrated care approaches.Trial Registration:ClinicalTrials.gov Identifier: NCT02458690.