Brachial Flow-mediated Dilation Research Articles

Acute hypotension attenuates brachial flow-mediated dilation in young healthy men.

This study aimed to test our hypothesis that acute hypotension attenuates brachial flow-mediated dilation (FMD) as an index of endothelial function in healthy humans. Twelve healthy men (21.8 ± 1.6years, body mass index; 22.2 ± 1.6kg/m2) participated in this study. Brachial FMD was measured in three trials: standardized FMD protocol (control trial), abrupt decrease in blood pressure (BP) via thigh cuff inflation-deflation (hypotension trial) and decrease in shear rate (SR) via a shortened forearm occlusion time (SR reduction trial). Brachial diameter and blood velocity were measured using Duplex ultrasound. Mean arterial pressure during reactive hyperaemia showed a marked decrease in the hypotension trial (- 23.7 ± 6.0mmHg), but not in the control and SR reduction trials. SR area under the curve was attenuated in the SR reduction trial (P < 0.001), but not in the control and hypotension trials (P = 0.316). Consequently, FMD was attenuated in the hypotension and SR reduction trials compared with that in the control trial (P = 0.003 and P = 0.043, respectively), and was attenuated to a greater extent in the hypotension trial compared with the SR reduction trial (P = 0.006; control, 6.9 ± 3.5%; hypotension, 3.5 ± 1.7%; SR reduction, 5.0 ± 2.2%). After adjusting FMD using SR, FMD remained attenuated in the hypotension trial (P = 0.014), but not in the SR reduction trial. Our findings indicate that arterial pressure as well as sympathetic nervous system activation could be an important determinant of FMD. Blunted FMD of peripheral arteries may be a rational response to restore BP and/or prevent further reduction of BP following acute hypotension in healthy humans.

P1573Chemotherapy-induced vasotoxicity in patients undergoing therapy for breast cancer

Abstract Background Cardiotoxicity is a well-known adverse effect of anthracycline and HER-2 monoclonal antibodies, however the vascular effects of these agents remain less-well studied. Purpose To explore the effects of breast chemotherapy on vascular function. Methods A total of 57 female patients undergoing breast diagnosed with breast cancer and scheduled for anthracycline-based and HER-2 chemotherapy were included in this study. At baseline, at 3, 6 and 12 months, patients underwent assessment of cardiac function by transthoracic echocardiography, endothelial function assessment by brachial flow mediated dilation (FMD) and assessment of arterial stiffness by carotid-radial pulse wave velocity (PWV) and augmentation index (Aix). Results There was a significant decrease in left ventricular ejection fraction (LVEF) overtime compared to baseline (A). This was paralleled by a significant decrease in brachial FMD at 6 months (B) and a significant increase in PWV compared to baseline (C). There was no significant change in Aix compared to baseline levels (D). Chemotherapy-induced cardiotoxicity (expressed by the change in LVEF) was not associated with either the change in FMD or PWV at 6 months. Conclusions Breast chemotherapy-induced cardiotoxicity is paralleled by vasotoxicity, which is manifested as endothelial dysfunction and increased arterial stiffness. Systemic vasotoxicity is not directly related to cardiotoxicity, suggesting that monitoring of both cardiac and vascular function could be useful in identifying early signs of cardiovascular toxicity.

P6136Intense daily cigarette smoking accelerates vascular damage of smokers with a moderate cumulative tobacco smoke exposure

Abstract Purpose Coronary artery disease death has been associated with increased cigarette smoking intensity. Aim of the study is to investigate the impact of cigarette smoking intensity on vascular function and structure changes among male smokers with similar age at starting smoking and moderate cumulative tobacco smoke exposure. Methods Indices of vascular function and structure including carotid-femoral pulse wave velocity (PWV), brachial flow-mediated dilation (bFMD), carotid intima media thickness (cIMT) and microvascular damage (penile vasculature) were measured in 118 smokers consuming up to 1 pack (20 cigarettes)/day and 58 patients smoking &gt;1 pack (20 cigarettes)/day. The two groups had a similar mean cigarette smoking exposure (32 pack/years). Microvascular damage was examined by measuring penile peak systolic velocity (PSV) with a dynamic penile color Doppler ultrasonography after intracavernous injection of prostanglandin E1. Lower PSV values indicate severe penile vascular disease. Results The individuals smoking more than 1 pack/day were 10 years younger than smokers consuming up to 1 pack/day, however systolic, diastolic blood pressure, body-mass index, fasting blood glucose levels, lipid profile, C-reactive protein and total testosterone concentration were similar between the two groups. Figure shows mean bFMD, penile PSV, PWV and cIMT of the two groups. Interestingly, despite the similar cumulative smoking exposure between the two groups, the younger in age individuals with the intense cigarette smoking history had significantly lower mean bFMD and penile PSV (all P&lt;0.05) and similar PWV and cIMT compared to the mean values of older subjects smoking up to 1 pack/day. Smoking intensity and vascular changes Conclusions Intense daily smoking accelerates damage of large arteries and significantly impairs microvascular and systemic endothelial function. Considering the predictive value of vascular biomarkers, the findings of this study imply the possibility that baseline daily smoking intensity could be a better summary measure of smoking-related cardiovascular risk among young heavy smokers, relative to total pack-years of smoking.

Impact of low-intensity resistance and whole-body vibration training on aortic hemodynamics and vascular function in postmenopausal women.

To examine the effects of low-intensity resistance exercise training (LIRET) and whole-body vibration training (WBVT) with an external weighted vest on arterial stiffness, wave reflection, brachial flow-mediated dilation (FMD), and physical performance in postmenopausal women. Thirty-three postmenopausal women were stratified by age, body mass index (BMI), and maximal voluntary contraction (MVC) (age, 65 ± 4 years; BMI, 23.3 ± 2.6 kg/m2; MVC, 17.4 ± 2.6 kg) and randomized into LIRET, WBVT, or a nonexercising control group for 12 weeks. Arterial stiffness, augmentation index (AIx), augmented pressure (AP), brachial FMD, gait speed and leg strength were measured at baseline and 12 weeks. WBVT induced improvements in pulse pressure amplification (PPA) (0.04 ± 0.02) compared to control (P = 0.048) and in wave reflection indices [AIx (-4.3 ± 1.4%) and AP (-2.9 ± 1.3 mmHg)] compared to LIRET (P = 0.039 and 0.048, respectively). WBVT (3.8 ± 1.4%) and LIRET (5.0 ± 1.5%) induced similar improvements in FMD compared to control (P = 0.029 and 0.008, respectively). WBVT and LIRET elicited similar increases in leg strength (P = 0.001 and 0.019, respectively), compared to no improvement in the control group. LIRET significantly increased gait speed compared to WBVT (P = 0.043). Although both WBVT and LIRET increased brachial artery FMD (systemic effect), WBVT seemed to be more efficacious in improving wave reflection and cardiac pulsatile load. Interestingly, LIRET elicited a significant improvement in gait speed. Both modalities seem effective in improving systemic endothelial function and muscle strength in postmenopausal women.

The effects of sympathetic activity induced by ice water on blood flow and brachial artery flow-mediated dilatation response in healthy volunteers.

ObjectiveTo investigate the association between sympathetic activity, reactive hyperemia and brachial artery flow-mediated dilation (FMD).BackgroundIt is claimed that major surgery has an impact on endothelial function, as observed by post-operative reduced brachial artery FMD response. However, another explanation for the observed reduced FMD response post-operatively may be sympathetic stress-induced reduction in blood flow.MethodsSeventeen healthy volunteers with a median age (25th-75th percentiles) of 23.5 (23–24.8) years were recruited. Participants’ brachial blood flow and FMD response were measured (i) during normal non-stress conditions (Normal1); (ii) during exposure to ice water; and (iii) afterwards, under normal non-stress conditions (Normal2). We continuously measured arterial blood pressure (Finometer), heart rate (ECG), skin blood flow of the index finger (laser Doppler), and brachial artery blood flow and diameter (Ultrasound Doppler). Measurements were taken at baseline; before a 5-min suprasystolic forearm occlusion; and following a 3-min post-occlusion, to measure reactive hyperemia and FMD.ResultsMedian (25th-75th percentiles) FMD response after exposure to ice water was reduced compared to non-stress conditions [4.9 (2.9–8.4) % during ice water vs. 9.7 (7.6–12.2) % Normal1 and 9.7 (6.4–10.3) % Normal2, P < 0.001]. Blood flow 60 s after cuff-deflation during ice water exposure was significantly reduced to 328 (289–421) mL compared to non-stress conditions (both P < 0.05). No differences were observed between Normal1 [446 (359–506) mL] and Normal2 [455 (365–515) mL] (both P > 0.05). Heart rate significantly increased during ice water exposure [67 (59–69) beats/min)] compared to 55 (49–60) beats/min during Normal1 and 54 (47–60) beats/min during Normal2 (both P < 0.05). MAP did not change during Normal1 [72 (64–84)] or during Normal2 [71 (65–81) mm Hg] (both P > 0.05), but increased to 86 (75–98) mm Hg during ice water exposure (P < 0.05).ConclusionsIncreased sympathetic activity resulted in decreased blood flow and brachial artery FMD response in healthy volunteers, independent of endothelial dysfunction. Future studies should adjust for blood flow when interpreting the FMD response.

Brachial flow-mediated dilation by continuous monitoring of arterial cross-section with ultrasound imaging.

Impairment of flow-mediated dilation of the brachial artery is a marker of endothelial dysfunction and often predisposes atherosclerosis and cardiovascular events. In this study, we propose a user-guided automated approach for monitoring arterial cross-section during hyperemic response to improve reproducibility and sensitivity of flow-mediated dilation. Ultrasound imaging of the brachial artery was performed in 11 volunteers in cross-sectional and in 5 volunteers in longitudinal view. During each examination, images were recorded continuously before and after inducing ischemia. Time-dilation curves of the brachial lumen cross-section were measured by user-guided automated segmentation of brachial images with the feed-forward active contour (FFAC) algorithm. %FMD was determined by the ratio of peak dilation to the baseline value. Each measurement was repeated twice in two sessions 1 h apart on the same arm to evaluate the reproducibility of the measurements. The intra-subject variation in flow-mediated dilation between two sessions (subject-specific) and inter-group variation in flow-mediated dilation with all the subjects within a session grouped together (group-specific) were measured for FFAC. The FFAC measurements were compared with the conventional diameter measurements made using echo tracking in longitudinal views. Flow-mediated dilation values for cross-sectional area were greater than those measured by diameter dilation: 33.1% for cross-sectional area compared to 22.5% for diameter. Group-specific flow-mediated dilation measurements for cross-sectional area were highly reproducible: 33.2% vs. 33.0% (p > 0.05) with coefficient of variation CV of 0.4%. The group-specific flow-mediated dilations measured by echo tracking for the two sessions were 21.1 vs. 23.9% with CV of 9%. Subject-specific CV for cross-sectional area by FFAC was 10% ± 2% versus 24% ± 10% for the conventional approach. Using correlation as a metric of evaluation also showed better performance for cross-sectional imaging: correlation coefficient, R, between two sessions for cross-sectional area was 0.92 versus 0.72 for the conventional approach based on diameter measurements. Peak dilation area measured by continuous automated monitoring of cross-sectional area of the brachial artery provides more reproducible and higher-sensitivity measurement of flow-mediated dilation compared to the conventional approach of using vascular diameter measured using longitudinal imaging.

Impaired endothelial function may predict treatment response in restless legs syndrome.

While dopaminergic dysfunction is believed to be a crucial role in restless legs syndrome (RLS), changes in peripheral microvasculature system such as peripheral hypoxia and altered skin temperature, have been found. This study aimed to investigate whether patients with RLS would have a cerebral and peripheral endothelial dysfunction, and this may have association with treatment responsiveness. We evaluated cerebral endothelial function using breath-holding index (BHI) on transcranial Doppler in bilateral middle cerebral artery (MCA), posterior cerebral artery (PCA) and basilar artery (BA) and peripheral endothelial function using brachial flow-mediated dilation (FMD) in 34 patients with RLS compared with age and sex-matched controls. The values of BHI in both MCA and BA were significantly lower in RLS group than control group. The values of FMD also were significantly lower in RLS patients. There was a weak correlation between BHI and FMD (p = 0.038 in Rt MCA, p = 0.032 in Lt MCA, p = 0.362 in BA) in RLS, but not in controls. BHI differed according to treatment responsiveness. (p < 0.005). Our study suggests that RLS patients have poorer cerebral and peripheral endothelial function than controls, showing an underlying mechanism of RLS and further evidence of a possible association between RLS and cardiovascular disease.

2357-PUB: Dapagliflozin for 52 Weeks Improves Diastolic Dysfunction and Vascular Reactivity in T2D

Background: SGLT2i proved efficacy in reducing cardiovascular morbidity and mortality in T2D patients at high cardiovascular risk. Aims: In real-word setting, we prospectively evaluated long-term effects of Dapagliflozin (DAPA) on left diastolic ventricular function (LDVF) and vascular reactivity in T2D patients without known cardiovascular disease. Population, Study and Methods: 13 patients (9 male, 57± 8 years, BMI 29.6± 3.6, HbA1c 8.9±1.2%, years of T2D 9±5, fasting glucose 185±51 mg/dl) initiated DAPA 10 mg daily as add-on to metformin. Following data were collected at baseline (T0), after 12 weeks (T1) and 52 weeks (T2) of treatment: blood pressure, anthropometrics, fasting glucose, HbA1c, eGFR and lipids. Ratio of the early (E) to late (A) ventricular filling velocities (E/A) was used to evaluate LDVF. Arterial stiffness was evaluated by Pulse Wave Velocity (PWV) and Augmentation Index (AIxHR75) with radial approach (SphygmoCor System). Endothelial function was assessed by non-invasive flow mediated dilatation (FMD). Results: We observed significant percent variation in HbA1c (T1 vs. T0 -17.9%, p=0.001; T2 vs. T0 -17.4%, p=0.01), fasting glucose (T1 vs. T0 -25.9%, p=0.002, T2 vs. T0 -31.8%, p=0.005) systolic blood pressure (T1 vs. T0 -6.7%, p=0.03; T2 vs. T0 -10.2% p=0.02) and BMI (T1 vs. T0 -3.3%, p=0.001; T2 vs. T0 -3%, p=0.02). Significant improvements from baseline of E/A ratio (T1 vs. T0 +15%, p=0.03; T2 vs. T0 +27.5%, p=0.003) and brachial FMD (T1 vs. T0 +50.7%, p=0.02; T2 vs. T0 +39.4%, p=0.04) were also seen. No significant changes in eGFR, lipids and arterial stiffness measures were seen. Conclusions: Intensification of treatment with DAPA 10 mg was accompanied by significant improvements in LVDF and endothelial-dependent vasodilation measures, which persist after 52 weeks of treatment. These preliminary observational results shed light on potential mechanisms responsible for cardiovascular protection with SGLT2i in T2D patients, even in absence of overt cardiovascular disease. Disclosure I. D'ippolito: None. E. De Carli: None. A. Andreadi: None. M. Romano: None. A. Galli: None. A. Capria: None. M. Massaro: None. P. Sbraccia: None. D. Della-Morte: None. A. Bellia: None. D. Lauro: None. Funding University of Rome

Coronary Microvascular Dysfunction by Myocardial Contrast Echocardiography in Nonelderly Patients Referred for Computed Tomographic Coronary Angiography

Microvascular dysfunction (MVD) is a potential cause of chest pain in younger individuals. The authors hypothesized that nonelderly patients referred for computed tomographic angiography (CTA) but without significant stenosis would have a high prevalence of MVD by myocardial contrast echocardiography (MCE). Secondary aims were to test whether the presence of nonobstructive coronary artery disease (CAD) or reduced brachial flow-mediated dilation (FMD) predicted MVD. Subjects ≤60years of age undergoing CTA were recruited if they had either no evidence of coronary plaque or evidence of mild CAD (<50% stenosis) and at least one high-risk plaque feature. Subjects underwent quantitative perfusion imaging using MCE at rest and during regadenoson vasodilator stress. MVD was defined as global or segmental delay of microvascular refill (≥2sec) during regadenoson. FMD of the brachial artery was also performed. Of the 29 patients in whom MCE could be performed, 12 (41%) had MVD. These subjects, compared with those with normal microvascular function, had lower hyperemic perfusion (mean, 236±68 vs 354±161 intensity units/sec; P=.02) and microvascular flux rate (mean, 1.6±0.4 vs 2.5±0.9sec-1; P=.002) on quantitative MCE. The degree of FMD was not significantly different in those with or without MVD (mean, 11±4% vs 9±4%; P=.32), and there was a poor correlation between results on stress MCE and FMD. Only eight of the 29 subjects were classified as having nonobstructive CAD. There were no groupwise differences in the prevalence of MVD function in those with versus without CAD (43% vs 38% for negative and positive findings on CTA, respectively, P=.79). MVD is a common finding in the nonelderly population referred for CTA for evaluation of possible CAD but without obstructive stenosis. Neither the presence of noncritical atherosclerotic disease nor abnormal FMD increases the likelihood for detecting MVD in this population.

Hyperbaric oxygen may improve vascular endothelial function in patients undergoing coronary stent implantation

Hyperbaric oxygen (HBO2) therapy improves myocardial function and reduces clinical restenosis in coronary arteries. This study aims to evaluate whether the HBO2 therapy can improve vascular endothelial dysfunction in patients undergoing coronary stent implantation. The retrospective study included 115 patients undergoing coronary stent implantation. Patients receiving HBO2 therapy were included in the HBO2 group (n=55) and those without HBO2 therapy were included as controls (n=60). The levels of brachial artery endothelial-dependent flow-mediated dilation (FMD), endothelial-independent nitrate-mediated dilatation (NMD), nitric oxide (NO), endothelin-1(ET-1), calcitonin gene-related peptide (CGRP) and high-sensitivity C-reactive protein (hs-CRP) were used to evaluate vascular endothelial function. There were no significant differences with regard to the above parameters at baseline in either group (p⟩0.05). In both the HBO2 and control groups the levels of FMD, NO and CGRP after treatment were significantly higher than those before treatment (p⟨0.05). The levels of hs-CRP and ET-1 after treatment were significantly lower than those before treatment (p⟨0.05). After treatment, the levels of FMD, NO and CGRP in the HBO2 group were significantly higher than those of the control group (p⟨0.05), whereas the hs-CRP and ET-1 levels were significantly lower than those of the control group (p⟨0.05). Using HBO2 therapy as an adjunct treatment in patients undergoing coronary stent implantation may significantly improve vascular endothelial function. HBO2 therapy may have the potential to alter the course of coronary artery disease in the future. Further randomized, multicenter, prospective studies are needed.

Maraviroc Intensification Modulates Atherosclerotic Progression in HIV-Suppressed Patients at High Cardiovascular Risk. A Randomized, Crossover Pilot Study.

BackgroundExperimental CCR5 antagonism with maraviroc in atherosclerosis-prone mice and preliminary data in humans suggest an anti-atherosclerotic effect of the drug. We assessed the impact of maraviroc treatment in persons living with HIV on subclinical indicators of atherosclerosis.MethodsPersons living with HIV on effective antiretroviral therapy (ART) including only protease inhibitors were recruited if they had a Framingham risk score >20% and brachial flow-mediated dilation (bFMD) <4%, as indices of high cardiovascular risk. Maraviroc (300 mg per os for 24 weeks) was administered, in addition to ongoing ART, to all patients using a crossover design. Brachial FMD, carotid-femoral pulse wave velocity (cfPWV), and carotid intima-media thickness (cIMT) were measured as markers of atherosclerosis. Vascular competence—as expressed by the ratio of circulating endothelial microparticles (EMPs) to endothelial progenitor cells (EPCs)—and markers of systemic inflammation and monocyte and platelet activation were assessed.ResultsMaraviroc treatment significantly improved bFMD, cfPWV, and cIMT by 66%, 11%, and 13%, respectively (P = .002, P = .022, P = .038, respectively). We also found a beneficial effect of maraviroc on the EMP/EPC ratio (P < .001) and platelet/leucocyte aggregates (P = .013). No significant changes in markers of systemic inflammation, monocyte activation, and microbial translocation were observed.ConclusionsMaraviroc led to significant improvements in several markers for cardiovascular risk, endothelial dysfunction, arterial stiffness, and early carotid atherosclerosis, which was accompanied by an increase of vascular competence, without seeming to affect systemic inflammation. Our data support the need for larger studies to test for any effects of maraviroc on preventing atherosclerosis-driven pathologies.

Brachial intima-media thickness is associated with coronary artery atherosclerosis in patients with diabetes mellitus.

Coronary artery calcification (CAC) as measured by computed tomography is a strong predictor of coronary artery disease. The brachial intima-media thickness (IMT) was recently reported to be associated with cardiovascular risk factors. This study investigated the association of brachial IMT with CAC, which is a marker of coronary artery atherosclerosis, in patients with diabetes. We enrolled 292 patients with diabetes (mean age, 65 ± 12years; 59% men) who underwent both endothelial function testing and computed tomography for risk assessment of coronary artery disease. Flow-mediated dilation (FMD) and IMT in the brachial artery were measured with a specialized machine. FMD was lower and brachial IMT was thicker in patients with than without CAC. The CAC score was significantly correlated with both brachial IMT and FMD, while the multivariate logistic analysis demonstrated that brachial IMT (> 0.32mm) but not FMD (< 5.1%) was significantly associated with the presence of CAC (odds ratio, 2.03; 95% confidence interval, 1.10-3.77; p = 0.02). The receiver operating characteristic curve analysis showed that the area under the curve for discriminating patients with CAC was 0.67 for IMT (p < 0.001) and 0.62 for FMD (p < 0.001). When patients were classified into four groups based on brachial IMT and FMD, the CAC score was higher in patients with thicker brachial IMT and lower FMD than in patients of the other groups (p < 0.001). Measurement of brachial IMT could be useful for the risk assessment of patients with diabetes.

Association of aortic stiffness, carotid intima-media thickness and endothelial function with cardiovascular events in metabolic syndrome subjects

Purpose: The objective of this study was to assess predictive value of various arterial markers for cardiovascular (CV) events in patients with metabolic syndrome (MetS).Materials and methods: A longitudinal study with the follow-up period of 3.9 ± 1.7 years investigated 2728 middle-aged (53.9 ± 6.2 years old, 63% women) MetS subjects without overt CV disease. The study cohort was comprised of the participants of the Lithuanian High Cardiovascular Risk primary prevention program. The baseline assessment included the evaluation of brachial flow-mediated dilatation (FMD), carotid intima-media thickness (cIMT), carotid stiffness index, aortic pulse wave velocity (aPWV), aortic augmentation index (AIx), and cardio-ankle vascular index). The data on the cardiovascular outcome (fatal or non-fatal myocardial infarction or stroke) was collected by using the databases of the two major national registries.Results: Over the follow-up period, 83 (3%) patients had at least one cardiovascular event. In a univariate analysis, occurrence of CV events was associated with the following parameters: higher mean blood pressure, aPWV, AIx and cIMT, and lower FMD (all p < .05).In Cox proportional hazard regression analysis, the occurrence of CV event was associated with an increase in aPWV (HR 1.29, 95% CI 1.04–1.60, p = .019), AIx (HR 1.53, 95% CI 1.16–2.02, p = .003), and cIMT (HR 1.31, 95% CI 1.14–1.50, p < .001), and with the decrease in FMD (HR 0.83, 95% CI 0.71–0.97, p = .016) even after the adjustment for age, gender, and common cardiometabolic risk factors.In a two-level survival trees analysis, we established that patients with cIMT > 794 mcm had higher CV risk (p < .001) and their prognosis was further compromised by aPWV > 11.1 m/s (p = .023). Meanwhile, in patients with cIMT ≤ 794mcm, the FMD cut-off point of 6.5% further stratified the risk (p = .003).Conclusions: In our prospective study, CV risk in the middle-aged patients with MetS was associated with an increase in cIMT and aPWV, and with a decrease in FMD.

Evaluation of endothelial function and arterial stiffness in obese individuals with insulin resistance.

Obesity is associated with metabolic imbalance, including insulin resistance and endothelial dysfunction. We aimed to evaluate clinical and vascular parameters in obese with or without insulin resistance. Participants ( n=39) were divided into two groups according to Homeostasis Model Assessment - Insulin Resistance lower (group 1) or higher (group 2) than 2.7. All patients were submitted to clinical, anthropometric, biochemical, vascular structure and endothelial function assessment. The mean age (53±9 vs. 52±7 years, p=0.784) and body mass index (34.3±4.1 vs. 35.2±3.9 kg/m2, p=0.464) were similar in both groups, and 74.4% were treated hypertensive subjects. Fasting glucose (84±7 vs. 97±18 mg/dl, p=0.004) and insulin (9.32±2.48 vs. 22.74±7.49 μU/ml, p<0.001) were higher in group 2. Group 2 presented lower HDL-cholesterol (59±14 vs. 42±12 mg/dl, p<0.001) and higher triglycerides (122±87 vs. 191±112 mg/dl, p=0.042) levels compared with group 1. HOMA-IR was correlated with abdominal circumference ( r=0.51, p=0.001), abdominal/hip ratio ( r=0.57, p<0.001) and triglycerides/HDL ratio ( r=0.53, p=0.001). Differences in brachial flow-mediated dilation did not reach statistical significance (10.2±6.2 vs. 7.9±4.7%, p=0.245). Carotid intima-media thickness, carotid-femoral pulse wave velocity (8.5±1.9 vs. 9.1±1.5 m/s, p=0.334) and central hemodynamic parameters were also similar between groups. Obese individuals with insulin resistance have higher visceral adiposity associated with impaired glucose and lipid metabolism. Endothelial function and arterial stiffness were similar between the groups, perhaps because of antihypertensive treatment in most of these subjects.

Is There an Association of Vascular Disease and Atherosclerosis in Children and Adolescents With Obesity and Non-alcoholic Fatty Liver Disease?

Carotid intima media thickness (cIMT) and brachial flow-mediated dilation (FMD) evaluated by ultrasound are non-invasive markers of atherosclerosis. Increased cIMT in adults has been correlated to early vascular damage. Several studies show similar correlations of elevated cIMT in children with obesity, hyperlipidemia, and metabolic syndrome. Additionally, several articles have correlated non-alcoholic fatty liver disease (NAFLD) with elevated cIMT, indicating early atherosclerosis. It is alarming that these vascular changes may be seen in children as young as 10 years of age. Children with NAFLD may also have an increased pulse wave velocity that correlates to increased arterial stiffness and increased left ventricular dimension, mass, and diastolic dysfunction. These articles are persuasive, indicating a correlation of Pediatric NAFLD and early vascular disease. However, study limitations include the use of elevated alanine aminotransferase (ALT) and echogenic changes on ultrasound that may have low accuracy to identify NAFLD. Ultrasound has low sensitivities and specificities for detection of NAFLD and therefore is not recommended for diagnosis. In comparison, studies that used liver biopsy or proton magnetic resonance spectroscopy to identify NAFLD did not find a correlation with elevated cIMT or reduction in FMD. Due to these conflicting findings, more studies looking at cIMT and FMD changes in children with NAFLD are needed with more accurate diagnostic methods for steatosis to identify if there truly is a correlation of increased liver steatosis to early atherosclerosis.

Tefillin use induces remote ischemic preconditioning pathways in healthy men.

The present study assessed whether tefillin use (tight, nonocclusive, wrapping of the arm) elicits a remote ischemic preconditioning (RIPC)-like effect in subjects with both acute and chronic use. RIPC, created by short bursts of ischemia-reperfusion, has not been successfully taken to the bedside. Several large population studies have found that Orthodox Jewish men (who wear tefillin almost daily) have decreased cardiovascular mortality compared with non-Orthodox counterparts. We hypothesized that tefillin use is a relevant component in triggering a preconditioning effect. Jewish men ( n = 20) were enrolled; 9 men were daily tefillin users (conditioned) and 11 men were nonusers of tefillin as controls (naïve). Subjects were evaluated for adherence to traditional Jewish practice, had vital signs measured, blood drawn for analysis of circulating cytokines and monocyte function, and underwent brachial flow-mediated dilation to evaluate vascular reactivity at baseline (basal) and after 30 min of using tefillin (acute treatment). Under basal conditions, both groups had similar peak systolic velocity (SV), diameter, and flow volume, although the conditioned group had higher SV at 120 s postdeflation ( P = 0.05). Acute tefillin use augmented artery diameter and flow volume in both groups, with conditioned subjects experiencing higher SV than control subjects at 90 and 120 s postdeflation ( P = 0.03 and P = 0.02, respectively). Conditioned subjects had decreased inflammation, monocyte migration and adhesion, and endothelial activation compared with control subjects at baseline. Acute use of tefillin did not significantly alter monocyte function in either group. In this pilot study, acute tefillin use improves vascular function, whereas chronic tefillin use is associated with an anti-inflammatory RIPC-like phenotype. NEW & NOTEWORTHY We hypothesized that tefillin use among Orthodox Jewish men (who practice a nonocclusive leather banding of their nondominant arm) will induce a remote ischemic preconditioning phenotype. Chronic use of tefillin in Orthodox Jewish men was associated with increased systolic velocity and attenuated inflammation and monocyte chemotaxis and adhesion versus Jewish men who do not wear tefillin. Acute use of tefillin in both populations augmented brachial artery diameter and blood flow but not inflammatory profiles compared with baseline.

Simple intermittent resistance activity mitigates the detrimental effect of prolonged unbroken sitting on arterial function in overweight and obese adults.

Prolonged sitting contributes to cardiovascular disease (CVD) risk. The underlying mechanisms are unknown but may include changes in arterial function and vasoactive mediators. We examined the effects of prolonged unbroken sitting, relative to regular active interruptions to sitting time, on arterial function in adults at increased CVD risk. In a randomized crossover trial, 19 sedentary overweight/obese adults (mean ± SD age 57 ± 12 yr) completed 2 laboratory-based conditions: 5 h uninterrupted sitting (SIT) and 5 h sitting interrupted every 30 min by 3 min of simple resistance activities (SRA). Femoral artery function [flow-mediated dilation (FMD)], blood flow, and shear rate were measured at 0 h, 30 min, 1 h, 2 h, and 5 h. Brachial FMD was assessed at 0 and 5 h. Plasma was collected hourly for measurement of endothelin-1 (ET-1), nitrates/nitrites, vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1). There was a significant decline in femoral artery FMD, averaged over 5 h in the SIT condition, relative to SRA (P < 0.001). Plasma ET-1 total area under the curve over 5 h increased in the SIT condition compared with SRA (P = 0.006). There was no significant difference between conditions in femoral or brachial shear rate, brachial FMD, nitrates/nitrites, VCAM-1, or ICAM-1 (P > 0.05 for all). Five hours of prolonged sitting, relative to regular interruptions to sitting time, impaired femoral artery vasodilator function and increased circulating ET-1 in overweight/obese adults. There is the need to build on this evidence beyond acute observations to better understand the potential longer-term vascular-related consequences of prolonged sitting.NEW & NOTEWORTHY This is the first study to examine the effect of prolonged sitting on arterial function in adults at increased cardiovascular disease risk. We have shown that 5 h of prolonged sitting, relative to regular interruptions to sitting time, impaired femoral artery vasodilator function and increased circulating endothelin-1 in overweight/obese adults. There is now the need to build on this evidence beyond acute observations to better understand the potential longer-term vascular-related consequences of prolonged sitting.

Effect of flaxseed consumption on flow-mediated dilation and inflammatory biomarkers in patients with coronary artery disease: a randomized controlled trial

Available data indicate a possible beneficial effect of flaxseed on cardiovascular disease, but limited studies have evaluated the effects of flaxseed on endothelial dysfunction and biomarkers of inflammation in patients with coronary artery disease (CAD). The purpose of the present study was to examine the effect of flaxseed consumption on flow-mediated dilation (FMD) and inflammatory markers in CAD patients. In this randomized controlled parallel trial, 50 patients with CAD of both genders were randomly allocated to 12 weeks consumption of flaxseed (30 g/day) or usual care control. Before and after the intervention, changes in brachial FMD and plasma high-sensitivity C-reactive protein (hs-CRP), interleukine-6 (IL-6), and tumor necrosis factor-α (TNF-α) were measured. Forty-four participants (aged 56.43 ± 8.21 years; BMI 26.65 ± 2.44 kg/m2) completed the study. No significant weight change was observed in either group. Compared to control (n = 23), flaxseed consumption (n = 21) was associated with improved FMD (mean of change from baseline was 5.1 vs -0.55%; p = 0.001 for the flaxseed and control, respectively). When compared to control, flaxseed consumption was associated with reduced inflammatory markers (mean of change from baseline for hs-CRP was -1.18 and -0.3 mg/L, p = 0.003; for IL-6 was -7.65 and -0.77 pg/mL, p = 0.017; for TNF-α was -34.73 and -2.18 pg/mL p = 0.001 in flaxseed and control, respectively). The results of this study indicate that by adding flaxseed to diet of CAD patients, it is possible to improve FMD and plasma levels of inflammatory markers.

Impaired Brachial Flow-Mediated Dilatation May Predict Symptomatic Intracranial Arterial Dissections

Background and PurposeSpontaneous intracranial arterial dissections are characterized by the sudden disruption of the internal elastic lamina in the intracranial arteries. The purpose of our retrospective study was to investigate whether patients with nontraumatic intracranial arterial dissections had normal endothelial function. MethodsThe study included symptomatic patients with nontraumatic intracranial arterial dissections who underwent an endothelial function test. Controls were selected from headache patients matched for sex and age. Endothelial function was assessed using flow-mediated dilatation. We investigated patients’ ankle brachial index and pulse wave velocity to determine the degree of atherosclerosis. Patient characteristics, brachial flow-mediated dilatation, ankle brachial index, and pulse wave velocity were compared between the 2 groups. ResultsDuring the study period, there were 22 patients with nontraumatic intracranial arterial dissections matched with 22 controls. Clinical characteristics were compared between the groups. Although there were no significant differences in ankle brachial index or pulse wave velocity between the 2 groups, patients with intracranial arterial dissections had lower flow-mediated dilatation values than controls (median flow-mediated dilatation, 3.95% in dissection patients versus 7.3% in controls, P = .0035). Brachial flow-mediated dilatation was impaired in symptomatic patients with nontraumatic intracranial arterial dissections despite the normal ankle brachial index and pulse wave velocity. ConclusionsImpaired brachial flow-mediated dilatation is a probable predictor of intracranial arterial dissections.

Improvement of arterial wall phenotype in subjects at moderate cardiovascular risk induced by very low-dose fluvastatin/valsartan combination: a pilot study.

The largest population that suffers from cardiovascular events are subjects at moderate cardiovascular risk. However, no effective and safe preventive treatment is available for this population. We investigated whether their arterial wall phenotype could be turned to a lower risk direction by low-dose fluvastatin/valsartan combination (low-flu/val). Twenty males at moderate cardiovascular risk (as classified by SCORE) were blindly randomized into the intervention group (N.=10, low-flu/val: 10 mg/20 mg) or control group (N.=10, placebo). At inclusion and after 30 days of treatment, brachial flow-mediated dilatation (FMD), β-stiffness coefficient, carotid pulse wave velocity (c-PWV), carotid-femoral PWV, Reactive Hyperemia Index, high-sensitivity C-reactive protein (hs-CRP), interleukin 6, vascular cell adhesion molecule 1, total antioxidant status and expression of several protective genes (SIRT1, mTOR, NF-κB1, NFE2L2, PRKAA1) were followed. Treatment resulted in improved FMD (from 3% to 4.2%, P=0.008), c-PWV (from 6.7 to 6.2 m/s, P=0.006), hs-CRP (from 5.39 to 3.35 mg/L, P=0.041) and SIRT1 expression (3.34-fold difference, P=0.047). No other vascular, inflammation and genetic parameters changed. The hs-CRP values after intervention correlated significantly with SIRT1 expression. The improved FMD persisted even 10 weeks after treatment discontinuation. The obtained changes were not followed by changes of lipids or blood pressure. Overall, the results revealed improvement in three different, although interrelated preventive arterial wall characteristics. This pilot study revealed that intervention with low-flu/val importantly shifts the arterial wall phenotype in a lower risk direction. This improvement could be interpolated into clinical benefits that remain to be further studied.