Decrease In Flow-mediated Dilation Research Articles

Enalapril Is Superior to Lisinopril in Improving Endothelial Function without a Difference in Blood-Pressure-Lowering Effects in Newly Diagnosed Hypertensives.

Here, we tested if lipophilicity affects the efficacy of ACE inhibitory drugs when used as the first therapy in newly identified hypertensives in a prospective study. We tested the differences in the cardiovascular efficacy of the hydrophilic lisinopril (8.3 ± 3.0 mg/day) and the lipophilic enalapril (5.5 ± 2.3 mg/day) (n = 59 patients). The cardiovascular parameters were determined using sonography (flow-mediated dilation (FMD) in the brachial artery, intima-media thickness of the carotid artery), 24 h ambulatory blood pressure monitoring (peripheral arterial blood pressure), and arteriography (aortic blood pressure, augmentation index, and pulse wave velocity) before and after the initiation of ACE inhibitor therapy. Both enalapril and lisinopril decreased blood pressure. However, lisinopril failed to improve arterial endothelial function (lack of effects on FMD) when compared to enalapril. Enalapril-mediated improved arterial endothelial function (FMD) positively correlated with its blood-pressure-lowering effect. In contrast, there was no correlation between the decrease in systolic blood pressure and FMD in the case of lisinopril treatment. The blood-pressure-lowering effects of ACE inhibitor drugs are independent of their lipophilicity. In contrast, the effects of ACE inhibition on arterial endothelial function are associated with lipophilicity: the hydrophilic lisinopril was unable to improve, while the lipophilic enalapril significantly improved endothelial function. Moreover, the effects on blood pressure and endothelial function did not correlate in lisinopril-treated patients, suggesting divergent mechanisms in the regulation of blood pressure and endothelial function upon ACE inhibitory treatment.

The effect of anthracycline-based chemotherapy on endothelial function and arterial stiffness in breast cancer patients

Abstract Introduction Cardiotoxicity restricts anthracycline and trastuzumab treatment of Human Epidermal Growth Factor Receptor 2 positive early breast cancer. Endothelial dysfunction and arteriosclerosis are significant cardiovascular risk factors. Purpose We studied the effect of anthracycline-based chemotherapy, with or without trastuzumab, on endothelium and arteriosclerosis in patients with breast cancer. Methods In this case-control study, 52 women with breast cancer and 104 women without breast cancer were examined longitudinally up to 15 months following (in the breast cancer group) initiation of chemotherapy. Arterial stiffness was evaluated through pulse wave velocity (PWV), while endothelial function via flow-mediated dilatation (FMD) at baseline (T0), 3 (T1), 6 (T2), and 15 (T3) months later. Results There was no difference between subjects with breast cancer and control in PWV and FMD at baseline. Longitudinally, participants with breast cancer exhibited considerable impairment of PWV and FMD compared to the control group (p for interaction < 0.001 for both parameters). In breast cancer patient there was a significant increase from T0 to T3 in PWV (7.43 ± 1.68 m/sec vs. 8.18 ± 2.00 m/sec, p = 0.01) and decrease in FMD (6.95 ± 2.86 % vs. 5.03 ± 2.83 %, p = 0.006). The addition of trastuzumab in the treatment did not have any effect on PWV (p = 0.74) or FMD (p = 0.91). Conclusions In patients with breast cancer, there is progression of endothelial dysfunction and arteriosclerosis up to 15 months following initiation of anthracycline-based chemotherapy. Trastuzumab has no additive effect on endothelial function or arterial stiffness.Figure 1Figure 2

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.

Prolonged impact of anti-cancer therapy on endothelial function and arterial stiffness in breast cancer patients

BackgroundCardiotoxicity restricts anthracycline and trastuzumab treatment of Human Epidermal Growth Factor Receptor 2 positive early breast cancer. Endothelial dysfunction and arteriosclerosis are significant cardiovascular risk factors. ObjectivesWe studied the effect of anthracycline-based chemotherapy, with or without trastuzumab, on endothelium and arteriosclerosis in patients with breast cancer. MethodsIn this case-control study, 52 women with breast cancer and 104 women without breast cancer were examined longitudinally up to 15 months following (in the breast cancer group) initiation of chemotherapy. Arterial stiffness was evaluated through pulse wave velocity (PWV), while endothelial function via flow-mediated dilatation (FMD) at baseline (T0), 3 (T1), 6 (T2), and 15 (T3) months later. ResultsThere was no difference between subjects with breast cancer and control in PWV and FMD at baseline. Longitudinally, participants with breast cancer exhibited considerable impairment of PWV and FMD compared to the control group (p for interaction <0.001 for both parameters). In breast cancer patients, there was a significant increase from T0 to T3 in PWV (7.43 ± 1.68 m/s vs. 8.18 ± 2.00 m/s, p = 0.01) and decrease in FMD (6.95 ± 2.86% vs. 5.03 ± 2.83%, p = 0.006). The addition of trastuzumab in the treatment did not have any effect on PWV (p = 0.74) or FMD (p = 0.91). ConclusionsIn patients with breast cancer, there is progression of endothelial dysfunction and arteriosclerosis up to 15 months following initiation of anthracycline-based chemotherapy. Trastuzumab has no additive effect on endothelial function or arterial stiffness.

Sex Differences in Vascular Response to Mental Stress and Adverse Cardiovascular Events Among Patients With Ischemic Heart Disease.

Microvascular measures of vascular dysfunction during acute mental stress may be important determinants of major adverse cardiovascular events (MACE), especially among younger and middle-aged women survivors of an acute myocardial infarction. In the MIMS2 study (Myocardial Infarction and Mental Stress 2), individuals who had been hospitalized for a myocardial infarction in the past 8 months were prospectively followed for 5 years. MACE was defined as a composite index of cardiovascular death and first/recurring events for nonfatal myocardial infarction and hospitalizations for heart failure. Reactive hyperemia index and flow-mediated dilation were used to measure microvascular and endothelial function, respectively, before and 30 minutes after a public-speaking mental stress task. Survival models for recurrent events were used to examine the association between vascular response to stress (difference between poststress and resting values) and MACE. Reactive hyperemia index and flow-mediated dilation were standardized in analyses. Of 263 patients (the mean age was 51 years; range, 25-61), 48% were women, and 65% were Black. During a median follow-up of 4.3 years, 64 patients had 141 adverse cardiovascular events (first and repeated). Worse microvascular response to stress (for each SD decrease in the reactive hyperemia index) was associated with 50% greater risk of MACE (hazard ratio, 1.50 [95% CI, 1.05-2.13]; P=0.03) among women only (sex interaction: P=0.03). Worse transient endothelial dysfunction in response to stress (for each SD decrease in flow-mediated dilation) was associated with a 35% greater risk of MACE (hazard ratio, 1.35 [95% CI, 1.07-1.71]; P=0.01), and the association was similar in women and men. Peripheral microvascular dysfunction with mental stress was associated with adverse events among women but not men. In contrast, endothelial dysfunction was similarly related to MACE among both men and women. These results suggest a female-specific mechanism linking psychological stress to adverse outcomes.

Abstract P407: Sex Differences in Microvascular Response to Mental Stress and Adverse Cardiovascular Events Among Patients With Ischemic Heart Disease

Introduction: Microvascular dysfunction during acute mental stress may be an important determinant of major adverse cardiovascular outcomes (MACE) especially among middle-aged women survivors of an acute myocardial infarction (MI). Hypothesis: There are sex differences in the association between microvascular dysfunction and MACE. Methods: The Myocardial Infarction and Mental Stress Study 2 enrolled individuals who had been hospitalized for an MI in the past 8 months at the age of 60 years or younger, with an oversampling of women. Reactive hyperemia index (RHI) was used to measure digital microvascular function before and 30 minutes after a public-speaking mental stress task. This assessment was contrasted with macrovascular endothelial function at the brachial artery through flow-mediated dilation (FMD). Participants were followed for 5-years, and MACE was defined as a composite of cardiovascular death, first/recurring events for nonfatal MI, and hospitalizations for heart failure. Cox proportional hazards models were used to examine vascular response to stress (difference between post-stress and resting values) and MACE adjusting for demographics, clinical risk factors, medications, psychological factors, and mental stress ischemia. Lower RHI and FMD values are indicative of greater microvascular and endothelial dysfunction, respectively. Results: Of 263 participants, the mean age was 51 years and 48% were women. There were 64 patients with 141 adverse cardiovascular events (first and repeated). In the overall sample, there was no significant association between microvascular response to stress and MACE, but there was a significant interaction with sex (p = 0.03). Each standard deviation decrease in RHI response to stress was associated with 50% greater risk of MACE (HR: 1.50, 95% CI: 1.05, 2.13) among women only, while no association was observed in men (HR 0.93, 95% CI: 0.69, 1.26). Transient endothelial dysfunction in response to stress (for each standard deviation decrease in FMD) was associated with 35% greater risk of MACE (HR: 1.35; 95% CI: 1.07, 1.71), and was similar in women and men. Conclusions: Peripheral microvascular dysfunction with mental stress is associated with MACE among women but not among men. In contrast, brachial artery endothelial dysfunction is similarly related to MACE among both men and women. These results suggest that microvascular dysfunction is a female-specific mechanism linking psychological stress to adverse outcomes.

Protective effect of N-acetyl cysteine on vascular function of young individuals after a bout of resistance exercise: a randomized placebo-controlled study

Abstract Background High intensity resistance exercise may temporarily induce vascular dysfunction mediated by pro-oxidant and pro-inflammatory pathways. Whether antioxidant supplements ameliorate this dysfunction has not been clarified. Purpose In the present study we aimed to evaluate the effect of the antioxidant N-acetyl cysteine (NAC) on vascular function after a bout of high-intensity resistance exercise in healthy young individuals. Methods In this randomized, cross-over, placebo-controlled study, ten healthy male volunteers (mean age 24.2±2.1 years) who exercised regularly were randomized to a daily oral administration of NAC or placebo during an 8-day recovery after an acute intense eccentric exercise protocol. In order to estimate changes in vascular parameters of interest -pulse wave velocity (PWV) and flow-mediated dilation (FMD)-, measurements were performed pre-exercise and across 6 pre-specified time points post-exercise (from 2 to 120 hours) in both arms. Blood samples were collected at baseline, immediately after exercise, 2 hours after exercise, and daily for eight consecutive days thereafter for the measurement of cellular components of the immune system. Results Muscle exercise induced a significant decrease in FMD in the placebo arm (F=2.74, p=0.017). This phenomenon was evident until 48 hours after exercise while FMD progressively returned to baseline values thereafter. In contrast, in the NAC arm, FMD did not decrease significantly (p&amp;gt;0.05 for all time-points). By linear mixed model analysis, a higher increase in CD4 cells levels correlated with preserved FMD (coefficient=0.025, p=0.046) in the placebo arm whereas this association was not significant (coefficient=0.004, p=0.811) in the NAC arm. PWV did not present significant fluctuations before and after exercise in either arm (p&amp;gt;0.05 for all comparisons). Conclusion A bout of eccentric exercise in young regularly training individuals induced endothelial dysfunction peaking at 48 hours, possibly partly mediated by an attenuated CD4 response. NAC exerted protective action on FMD, indicating that oxidative stress may be implicated in vivo in this setting. Funding Acknowledgement Type of funding sources: None.

Laser Doppler flowmetry evaluation of skin microvascular endothelial function in patients with metabolic syndrome.

Metabolic syndrome (MetS) is associated with high cardiovascular morbidity and mortality, and endothelial dysfunction is an early pathogenetic event in the MetS. Lifestyle changes and pharmacological intervention might partly restore endothelial function in MetS. Whereas an optimal non-invasive test for endothelial dysfunction is still being sought, the aim of this study was to assess the relationship between changes in skin microvascular endothelial function, detected by Laser Doppler flowmetry, and cardiovascular risk factors (CVRFs) of patients with MetS. 3081 patients (1865 women and 1216 men, mean age 53±6years) with MetS were enrolled in the study, which was conducted during the period of 2010-2014 at Vilnius University Hospital Santaros Klinikos. Skin microvascular endothelial function was evaluated using the Laser Doppler flowmetry in combination with the post-occlusive reactive hyperaemia test. The percentage change of flow from peak to the rest flow (PF-RF) was calculated and used as the main measure of endothelial function. The study showed that decrease in flow-mediated dilatation reflected by PF-RF was associated with increased triglycerides (p=0.002), male sex (p<0.001), and diabetes (p=0.002). Patients with quite a few CVRFs (body mass index ≥25kg/m2, smoking, diabetes, arterial hypertension, a positive history of dyslipidaemia) had significantly lower PF-RF score than patients only with one of these risk factors (p<0.001). Changes in skin microvascular endothelial function are significantly associated with most CVRFs and depend on the number of CVRFs.

COVID-19 IS ASSOCIATED WITH ENDOTHELIAL DYSFUNCTION: A META-ANALYSIS OF OBSERVATIONAL STUDIES

Objective: A number of studies have indicated a deleterious effect of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection on endothelial function of enrolled subjects, further impairing during post-infectious stage. Endothelial function might indeed have a prognostic role in coronavirus disease-19 (COVID-19). Herein we sought to determine the effect of SARS-CoV-2 on endothelial function as quantified by flow-mediated dilation (FMD). Design and method: We searched the PubMed database from inception till 21st December, 2021, for observational studies assessing the impact of SARS-CoV-2 on endothelial function either in the in-hospital or the outpatient setting. We set as primary efficacy outcome the mean difference in FMD between infected patients and healthy controls. Results: We pooled data from 5 observational studies in a total of 541 enrolled subjects. One study enrolled children, while the rest 4 enrolled adults. Overall, COVID-19 induced a significant decrease in FMD by 3.29% (95% CI; -4.57 to -2.01, I2 = 81%) compared to healthy controls. Conclusions: Despite being preliminary, these results suggest a significant effect of SARS-CoV-2 on endothelial system, leading to significant endothelial dysfunction. Prognostic implications of that effect have to be determined in prospective studies.

Effect of Acute Isometric Handgrip Exercise on Vascular Function in Children with Congenital Heart Disease

ObjectiveThe reactivity of conduit vessels such as the brachial artery is important in influencing arterial diameter, and subsequently, blood flow. Flow‐mediated dilation (FMD) measures vessel reactivity. The increase in shear stimuli from transient arterial occlusion enhances arterial diameter in an endothelial‐dependent manner, and this is thought to be impaired in individuals with congenital heart disease (CHD). Isometric handgrip (IHG) exercise is a proposed intervention to improve vessel reactivity by optimizing the shear stimuli to provoke changes in arterial diameter. Indeed, IHG training has been found to improve FMD in healthy adults and children. Whether IHG training improves endothelial dysfunction in CHD remains unknown. Improving vessel reactivity in the young becomes increasingly important in optimizing vascular health into adulthood. The effects of acute IHG exercise on the brachial artery were examined in children with CHD.HypothesisWe tested the hypothesis that acute IHG exercise would increase FMD in children with CHD.MethodsFour subjects with CHD (mean, 13 ± 1 year, 3 female) completed a single session of 4 × 2 mins of acute IHG (30% maximum voluntary contraction using the right hand) with 1‐min rest intervals between bouts. Before and after IHG exercise, the right brachial artery was imaged with Duplex ultrasound using a 1‐min baseline, 5 mins of forearm circulatory occlusion, followed by 3 mins of cuff deflation. Blood pressure and heart rate were measured continuously.ResultsPre‐FMD (baseline) mean arterial pressure (pre: 102 ± 17 mmHg vs. post: 110 ± 16 mmHg, p = 0.496) and heart rate (pre: 75 ± 13 bpm vs. post: 66 ± 5 bpm, p = 0.253) were not different. Baseline brachial artery diameter increased following acute IHG in 3 of 4 subjects (pre: 3.11 ± 0.45 mm vs. post: 3.23 ± 0.39 mm, Cohen’s d = 0.3). Peak shear rate was greater post‐IHG in 3 of 4 subjects (pre: 995 ± 346 sec‐1vs. post: 1158 ± 501 sec‐1, Cohen’s d = 0.4). FMD% (4.7% vs. 6.3% and 8.2% vs. 10.5%) and FMD% normalized to shear rate area under the curve (AUC) ratio (2.2E‐5 vs. 7.4E‐5 a.u. and 3.1E‐5 vs. 4.3E‐5 a.u., Cohen’s d = 2.0) increased post‐IHG in 2 of 4 subjects. When brachial artery diameter increased, peak shear rate, FMD%, and FMD% normalized to shear rate AUC improved post‐IHG in 2/3 subjects whereas subject four showed a decrease in brachial artery diameter, FMD% and FMD% normalized to shear rate AUC, with the exception of peak shear rate post‐IHG.ConclusionFavorable changes in brachial artery diameter, peak shear rate, FMD% and FMD% normalized to shear rate AUC following acute IHG may be a promising intervention for improving vascular tone and endothelial function in children with CHD.

The effects of alcohol consumption on flow-mediated dilation in humans: A systematic review.

Changes in endothelial function may contribute to the positive and negative effects of alcohol consumption on cardiovascular conditions, such as hypertension and coronary artery disease. Numerous studies have used brachial artery flow‐mediated dilation (FMD) to examine the effects of alcohol consumption on endothelial function in humans. However, the findings are inconsistent and may be due to multiple factors such as heterogeneity in subject characteristics, the alcohol use pattern, and amount/dose of alcohol consumed. Therefore, the aim of this systematic review was to investigate the effect of alcohol consumption on brachial artery FMD in humans considering the above‐mentioned factors. This review found that while light to moderate alcohol consumption may have minimal effects on FMD, heavy alcohol consumption was associated with a decrease in FMD. However, most of the published studies included healthy, younger, and male individuals, limiting generalizability to other populations. Future studies should include more women, older subjects, and those from diverse and underrepresented backgrounds.

The Effects of Acute Exposure to Prolonged Sitting, With and Without Interruption, on Vascular Function Among Adults: A Meta-analysis.

Exposure to acute prolonged sitting can result in vascular dysfunction, particularly within the legs. This vascular dysfunction, assessed using flow-mediated dilation (FMD), is likely the consequence of decreased blood flow-induced shear stress. With mixed success, several sitting interruption strategies have been trialled to preserve vascular function. The objectives of this meta-analysis were to (1) assess the effects of acute prolonged sitting exposure on vascular function in the upper- and lower-limb arteries, and (2) evaluate the effectiveness of sitting interruption strategies in preserving vascular function. Sub-group analyses were conducted to determine whether artery location or interruption modality explain heterogeneity. Electronic databases (PubMed, Web of Science, SPORTDiscus, and Google Scholar) were searched from inception to January 2020. Reference lists of eligible studies and relevant reviews were also checked. Inclusion criteria for objective (1) were: (i) FMD% was assessed pre- and post-sitting; (ii) studies were either randomised-controlled, randomised-crossover, or quasi-experimental trials; (iii) the sitting period was ≥ 1h; and (iv) participants were healthy non-smoking adults (≥ 18years), and free of vascular-acting medication and disease at the time of testing. Additional inclusion criteria for objective (2) were: (i) the interruption strategy must have been during the sitting period; (ii) there was a control (uninterrupted sitting) group/arm; and (iii) the interruption strategy must have involved the participants actively moving their lower- or upper-limbs. One thousand eight hundred and two articles were identified, of which 17 (22 trials, n = 269) met inclusion criteria for objective (1). Of those 17 articles, 6 studies (9 trials, n = 127) met the inclusion criteria for objective (2). Weighted mean differences (WMD), 95% confidence intervals (95% CI), and standardised mean difference (SMD) were calculated for all trials using random-effects meta-analysis modelling. SMD was used to determine the magnitude of effect, where < 0.2, 0.2, 0.5, and 0.8 was defined as trivial, small, moderate, and large respectively. (1) Random-effects modelling showed uninterrupted bouts of prolonged sitting resulted in a significant decrease in FMD% (WMD = - 2.12%, 95% CI - 2.66 to - 1.59, SMD = 0.84). Subgroup analysis revealed reductions in lower- but not upper-limb FMD%. (2) Random-effects modelling showed that interrupting bouts of sitting resulted in a significantly higher FMD% compared to uninterrupted sitting (WMD = 1.91%, 95% CI 0.40 to 3.42, SMD = 0.57). Subgroup analyses failed to identify an optimum interruption strategy but revealed moderate non-significant effects for aerobic interventions (WMD = 2.17%, 95% CI - 0.34 to 4.67, SMD = 0.69) and simple resistance activities (WMD = 2.40%, 95% CI - 0.08 to 4.88, SMD = 0.55) and a trivial effect for standing interruptions (WMD = 0.24%, 95% CI - 0.90 to 1.38, SMD = 0.16). Exposure to acute prolonged sitting leads to significant vascular dysfunction in arteries of the lower, but not upper, limbs. The limited available data indicate that vascular dysfunction can be prevented by regularly interrupting sitting, particularly with aerobic or simple resistance activities.

Validation Of Flow-mediated Slowing As A Measure Of Endothelial Function

BACKGROUND: Flow-Mediated Slowing (FMS) is a potentially simple, automated and user-objective test for assessing endothelial function. FMS can be defined as the minimum pulse wave velocity (PWVmin) during reactive hyperemia. PURPOSE: The purpose of this study was to determine the effects of acute endothelial dysfunction on PWVmin. It was hypothesized that endothelial dysfunction would increase PWVmin. METHODS: 22 young, healthy adults (23.8 yrs ± 4.1, 73% F, 22.8 kg/m2 ± 2.8) underwent simultaneous assessment of Flow-Mediated Dilation (FMD) and PWVmin at baseline and immediately following 30min of an endothelial dysfunction protocol. FMD is the current gold-standard test of endothelial function and was used to confirm endothelial dysfunction. Endothelial dysfunction was induced by increasing retrograde shear stress in the brachial artery via inflation of a pneumatic tourniquet to 75 mm Hg around the forearm. PWV was measured from the upper-arm to the wrist using an oscillometric-based device, and brachial FMD was measured using duplex Doppler ultrasound. FMD (%) was calculated as the mean increase in diameter during reactive hyperemia, and PWVmin as the minimum pulse wave velocity during reactive hyperemia. Linear mixed models were used to assess baseline versus endothelial dysfunction changes in PWVmin and FMD, controlling for within-subject changes in mean arterial pressure. Inter-individual associations between baseline PWVmin and FMD were examined using Pearson’s product moment correlation, and intra-individual associations between change (baseline vs. endothelial dysfunction) in PWV and change in FMD using the repeated measures correlation package for R. RESULTS: The endothelial dysfunction protocol resulted in large effect size (ES) decrease in FMD (∆ = -3.10, 95%CI: -4.15, -2.05, ES = -1.3), and a moderate significant increase in PWVmin (∆ = 0.16, 95%CI: 0.05, 0.28, ES = 0.6). There was a moderate inter-individual association between FMD and PWVmin (r = 0.46), and a large intra-individual association between FMD and PWVmin (r = -0.61). CONCLUSIONS: Acute changes in PWVmin may be a user-objective, automated, and viable tool for monitoring acute changes in endothelial function.

Endothelium function dependence of acute changes in pulse wave velocity and flow-mediated slowing

Flow-mediated slowing (FMS), defined as the minimum pulse wave velocity (PWVmin) during reactive hyperemia, is potentially a simple, user-objective test for examining endothelial function. The purpose of the current study was to determine the effects of a known endothelial dysfunction protocol on arm PWV and PWVmin. Complete data were successfully collected in 22 out of 23 healthy adults (23.8 years [SD 4.1], 16 F, 22.8 kg/m2 [SD 2.8]). Local endothelial dysfunction was induced by increasing retrograde shear stress in the upper arm, through inflation of a distal (forearm) tourniquet to 75 mmHg, for 30 min. Pre- and post-endothelial dysfunction, PWV was measured followed by simultaneous assessment of PWVmin and flow-mediated dilation (FMD). PWV was measured between the upper arm and wrist using an oscillometric device, and brachial FMD using ultrasound. FMD (%) and PWVmin (m/s) were calculated as the maximum increase in diameter and minimum PWV during reactive hyperemia, respectively. Endothelial dysfunction resulted in a large effect size (ES) decrease in FMD (∆ = −3.10%; 95% CI: –4.15, –2.05; ES = −1.3), and a moderate increase in PWV (∆ = 0.38 m/s; 95% CI: 0.07, 0.69; ES = 0.5) and PWVmin (∆ = 0.16 m/s; 95% CI: 0.05, 0.28; ES = 0.6). There was a large intra-individual (pre- vs post-endothelial dysfunction) association between FMD and PWVmin (r = −0.61; 95% CI: –0.82, –0.24). In conclusion, acute change in PWV and PWVmin are at least partially driven by changes in endothelial function.

İnvestigation of endothelial dysfunction in children with acute rheumatic fever.

Background:Acute rheumatic fever (ARF) is an important cause of valvular heart disease in children. Endothelial dysfunction plays an important role in the pathogenesis of valvular heart diseases. The role of endothelial dysfunction in valvular heart diseases due to ARF is not exactly known. In ARF, autoimmune injury, inflammation, oxidative stress, and impairment of nitric oxide in valvular endothelium may be the causes of endothelial dysfunction. The purpose of this study is to evaluate endothelial dysfunction and arterial stiffness in children with ARF.Materials and Methods:Thirty-six patients diagnosed with ARF (the mean age was 11.80 ± 2.82 years) and 36 volunteered individuals with similar age, sex, and body mass index were included in the study. The study groups were compared in terms of M-mode echocardiography parameters, carotid arterial strain (CAS), beta-stiffness index (βSI), and flow-mediated dilation (FMD).Results:In patients with ARF, there was a decrease in FMD% (10.36 ± 7.26 and 12.76 ± 4.59; P < 0.001) compared to the control group. In addition, CAS (0.16 ± 0.06 and 0.18 ± 0.08; P = 0.44) and βSI (3.65 ± 1.61 and 3.57 ± 2.38; P = 0.24) were similar in the patient and the control groups. Furthermore, no correlation was detected between decreased FMD value and mitral regurgitation (r = −0.07; P = 0.66), aortic regurgitation (r = −0.04; P = 0.78), CAS (r = −0.08; P = 0.61), and βSİ (r = −0.20; P = 0.22).Conclusion:In our study, a decrease in FMD value, which is a marker of endothelial dysfunction, was found in children with rheumatic carditis.

The Effect of Perimenopausal Transdermal Estradiol and Micronized Progesterone on Markers of Risk for Arterial Disease.

The arterial effects of hormone therapy remain controversial. This study tested the effects of transdermal estradiol plus intermittent micronized progesterone (TE + IMP) in healthy perimenopausal and early postmenopausal women on several mechanisms involved in the pathophysiology of arterial disease. Healthy perimenopausal and early postmenopausal women, ages 45 to 60 years, were enrolled in this randomized, double-blind, placebo-controlled trial. Women were randomized to receive TE (0.1 mg/day) + IMP (200 mg/day for 12 days) or identical placebo patches and pills for 12 months. Outcomes included: change in stress reactivity composite z-score (combining inflammatory, cortisol, and hemodynamic responses to a standardized psychological laboratory stressor); flow-mediated dilation (FMD) of the brachial artery (an index of vascular endothelial function); baroreflex sensitivity; and metabolic risk (presence of the metabolic syndrome or insulin resistance), all assessed at baseline and at months 6 and 12. Of 172 women enrolled, those assigned to TE + IMP tended to have higher resting baroreflex sensitivity than those assigned to placebo across the 6- and 12-month visits. Although treatment groups did not differ in terms of the other prespecified outcomes, a significant treatment-by-age interaction was found for FMD and stress reactivity such that an age-related decrease in FMD and increase in stress reactivity were seen among women assigned to placebo but not those assigned to TE + IMP. Women on TE + IMP also had lower resting diastolic blood pressure, lower levels of low-density lipoprotein cholesterol, and higher baroreflex sensitivity during stress testing. TE + IMP tended to improve cardiac autonomic control and prevented age-related changes in stress reactivity and endothelial function among healthy perimenopausal and early postmenopausal women.

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.

Aerobic or resistance exercise performed the previous day does not attenuate postprandial hyperglycemia-induced endothelial dysfunction in overweight/obese adults.

Postprandial hyperglycemia (PPH) impairs vascular endothelial function (VEF). A single bout of aerobic exercise (AE) attenuates PPH-induced decreases in brachial artery flow-mediated dilation (FMD), a non-invasive measure of VEF, in healthy adults for up to 17h post-exercise. Studies examining the effects of resistance exercise (RE) on postprandial FMD responses are lacking. We hypothesized that a single bout of exercise performed the prior evening would attenuate PPH-induced decreases in FMD, independent of exercise modality. In a randomized, cross-over design, overweight/obese adults [n = 11 (8 women); 22 ± 4years; 32.3 ± 5.8kgm-2] completed 3 separate trials: control (seated rest), AE (30min at ~ 60% VO2max), or whole-body RE (30min, 6 exercises, 3 × 10-repetition maximum). Each trial occurred 14-17h prior to an oral glucose tolerance test (OGTT). Brachial artery FMD and plasma glucose and insulin were measured prior to and at 30-min intervals for 2h following the OGTT. Repeated-measures ANOVA and Bonferroni post hoc tests were used to evaluate differences within and between trials. Trials occurred 15.3 ± 1.0h prior to the OGTT. Relative to baseline, FMD transiently decreased (P < 0.05) at 30-60min post-ingestion, plasma glucose increased (P < 0.01) at 30-90min post-ingestion, and plasma insulin increased (P < 0.01) at 30-120min post-ingestion. No between trial differences were observed for FMD, glucose, or insulin. Aerobic or resistance exercise performed the evening prior to an OGTT does not attenuate postprandial decreases in brachial artery FMD in overweight/obese adults.

Altered bioavailability of epoxyeicosatrienoic acids is associated with conduit artery endothelial dysfunction in type 2 diabetic patients

BackgroundThis pathophysiological study addressed the hypothesis that soluble epoxide hydrolase (sEH), which metabolizes the vasodilator and anti-inflammatory epoxyeicosatrienoic acids (EETs) to dihydroxyeicosatrienoic acids (DHETs), contributes to conduit artery endothelial dysfunction in type 2 diabetes.Methods and resultsRadial artery endothelium-dependent flow-mediated dilatation in response to hand skin heating was reduced in essential hypertensive patients (n = 9) and type 2 diabetic subjects with (n = 19) or without hypertension (n = 10) compared to healthy subjects (n = 36), taking into consideration cardiovascular risk factors, flow stimulus and endothelium-independent dilatation to glyceryl trinitrate. Diabetic patients but not non-diabetic hypertensive subjects displayed elevated whole blood reactive oxygen species levels and loss of NO release during heating, assessed by measuring local plasma nitrite variation. Moreover, plasma levels of EET regioisomers increased during heating in healthy subjects, did not change in hypertensive patients and decreased in diabetic patients. Correlation analysis showed in the overall population that the less NO and EETs bioavailability increases during heating, the more flow-mediated dilatation is reduced. The expression and activity of sEH, measured in isolated peripheral blood mononuclear cells, was elevated in diabetic but not hypertensive patients, leading to increased EETs conversion to DHETs. Finally, hyperglycemic and hyperinsulinemic euglycemic clamps induced a decrease in flow-mediated dilatation in healthy subjects and this was associated with an altered EETs release during heating.ConclusionsThese results demonstrate that an increased EETs degradation by sEH and altered NO bioavailability are associated with conduit artery endothelial dysfunction in type 2 diabetic patients independently from their hypertensive status. The hyperinsulinemic and hyperglycemic state in these patients may contribute to these alterations.Trial registration NCT02311075. Registered December 8, 2014.

Cardiovascular risk and the possibility of its correction in women with premature ovarian insufficiency

Since recently, the association of premature ovarian insufficiency (POI) with an increased risk of mortality and morbidity caused by cardiovascular diseases (CVD) has been extensively discussed in the context of early detection and prevention of CVD in these patients.Aim: to evaluate the relative cardiovascular risk (CV risk) before and after hormone replacement therapy (HRT) in women with POI.Materials and methods. The study included 170 women aged from 18 to 40; among them, 85 women with POI and 85 women with regular periods. We evaluated the usual CV risk factors: smoking habits, arterial blood pressure, total cholesterol (TC), low-density lipoproteins (LDL), high-density lipoproteins; in addition, we determined apolipoprotein B (Apo B), high-sensitivity C-reactive protein (hs-CRP), uric acid, and endotelin-1, as well as the functional markers: the right and left carotid intima-media thickness (CIMT) and the brachial artery flow-mediated dilatation (FMD). The CV risk was calculated using the relative risk SCORE scale before and after HRT lasted for 12 months.Results. In the POI group, there were 3.8 times more women with a moderate CV risk (per the SCORE scale), whereas in the POI-free group, women with a low CV risk dominated. In addition, the levels of CV risk markers were 4-fold higher in patients with POI (high levels of Apo B, hs-CRP and uric acid, increased CIMT bilaterally, decreased FMD in the brachial artery). Cyclic HRT during 12 months contributed to the lipid profile normalization, decrease in TC, LDL and FMD in the brachial artery as well as to the decrease of relative CV risk in general.Conclusion. The estrogen deficiency in patients with POI is an independent factor in the increased relative risk of CVD. The HRT has anti-atherogenic, antiinflammatory, and angioprotective effects, regulates the production of endothelium-dependent factors of vasoconstriction and vasodilation, leading to a reduction in the relative risk of CVD in general.