Endothelium-dependent Flow-mediated Vasodilation Research Articles

(134) Early Impact of Androgen Deprivation Therapy on Endothelial Function and Metabolic Parameters in Prostate Cancer Patients: A Prospective Study

Abstract Introduction Androgen deprivation therapy (ADT) is considered one of the mainstays in the treatment of prostate cancer. ADT slows cancer progression, alleviates cancer-related symptoms, and is associated with survival gains. Despite these proven benefits, this treatment is related to several side effects, such as increased cardiovascular risk, changes in body composition and various metabolic changes. Although the well-established association between circulating testosterone level and endothelial integrity, the direct effects of ADT on endothelial function remain controversial. Objective This study aimed to investigate the impact of ADT on endothelial function, through the analysis of vascular parameters of the brachial artery and measurement of serum inflammatory markers. It was also our aim to evaluate the early impact of ADT on body composition and metabolic parameters. Methods We prospectively evaluated men with moderate to high-risk prostate cancer treated with ADT from January to December 2022 at our institution. Smokers and those who quit smoking less than five years ago, decompensated diabetics (glycated hemoglobin > 9%) and those who had already had a cardiovascular event were excluded. High-resolution B-mode ultrasound was used to assess vascular diameter and endothelium-dependent flow-mediated vasodilation (FMD) of the brachial artery. Our metabolic and inflammatory profile included measurement of serum total cholesterol and fractions, triglycerides, fasting glucose, glycated hemoglobin, basal insulin, C-reactive protein and assessment of body fat distribution through bioelectrical impedance. Subjects were evaluated at baseline and 3 months after starting ADT with goserelin acetate 10.80 mg. Results A total of 32 men were included. The mean age was 69 years and the prevalence of diabetes was 31.25%. FMD demonstrated a worsening trend after ADT, which did not reach statistical significance after 3 months (mean 3.39 ± 6.83 vs 1.16 ± 7.65; p = 0.14) (figure 1). Baseline brachial artery diameter also showed a tendency to worsen with ADT compared to baseline (0.44 ± 0.06 vs 0.42 ± 0.06; p = 0.06). With regard to the metabolic profile, ADT significantly increased insulin resistance: fasting glucose (mean 104.10 ± 18.96 vs 110.60 ± 25.29; p = 0.01), fasting insulin levels (mean 13.05 ± 8.76 vs 16.82 ± 11.36; p = 0.003), glycated hemoglobin (mean 5.89% ± 0.46 vs 6.15% ± 0.67; p = 0.008) and homeostatic model assessment insulin resistance (mean 3.47 ± 2.55 vs 5.05 ± 4.50; p = 0.005) increased significantly after 3 months. Triglycerides concentrations (mean 142.30 ± 69.66 vs 165.50 ± 93.04; p = 0.03) were higher after 3 months of ADT. Abdominal circumference (mean 98.66 ± 10.16 vs 99.76 ± 9.39; p = 0.02) and body mass index (mean 27.46 ± 4.06 vs 27.76 ± 3.89; p = 0.02) also increased after ADT. Conclusions Although not statistically significant, the present study demonstrated a trend towards a decrease in brachial artery FMD. We also observed an important and surprisingly early worsening of the metabolic profile with ADT, especially increased insulin resistance and dyslipidemia, which represent well-established risk factors for cardiovascular events. Disclosure No.

Subclinical atherosclerosis in young adults predicting cardiovascular disease: The Cardiovascular Risk in Young Finns Study

Background and aimsAtherosclerosis is accompanied by pre-clinical vascular changes that can be detected using ultrasound imaging. We examined the value of such pre-clinical features in identifying young adults who are at risk of developing atherosclerotic cardiovascular disease (ASCVD). MethodsA total of 2641 individuals free of ASCVD were examined at the mean age of 32 years (range 24–45 years) for carotid artery intima-media thickness (IMT) and carotid plaques, carotid artery elasticity, and brachial artery flow-mediated endothelium-dependent vasodilation (FMD). The average follow-up time to event/censoring was 16 years (range 1–17 years). ResultsSixty-seven individuals developed ASCVD (incidence 2.5%). The lowest incidence (1.1%) was observed among those who were estimated of having low risk according to the SCORE2 risk algorithm (<2.5% 10-year risk) and who did not have plaque or high IMT (upper decile). The highest incidence (11.0%) was among those who were estimated of having a high risk (≥2.5% 10-year risk) and had positive ultrasound scan for carotid plaque and/or high IMT (upper decile). Carotid plaque and high IMT remained independently associated with higher risk in multivariate models. The distributions of carotid elasticity indices and brachial FMD did not differ between cases and non-cases. ConclusionsScreening for carotid plaque and high IMT in young adults may help identify individuals at high risk for future ASCVD.

Seasonal variations in endothelium-dependent flow-mediated vasodilation and endothelium-independent nitroglycerine-induced vasodilation.

Cardiovascular mortality has been shown to vary seasonally. However, it has not been determined whether vascular function is affected by the season. The purpose of this study was to investigate the associations of vascular function with season and outdoor temperature. Between April 2007 and March 2022, measurements of flow-mediated vasodilation (FMD) of the brachial artery as an index of endothelial function and nitroglycerine-induced vasodilation (NID) as an index of endothelium-independent vasodilation were performed in 2190 subjects. There was no significant seasonal difference in FMD (spring, 3.9 ± 3.1%; summer, 3.5 ± 3.0%; fall, 3.7 ± 3.0%; winter, 3.6 ± 3.2%; P = 0.14). There was no significant correlation between FMD and daily mean outdoor temperature (r = -0.02, P = 0.25). Multivariate analyses revealed that neither season (β = -0.020, P = 0.31) nor outdoor temperature (β = 0.005, P = 0.81) was significantly associated with FMD after adjustment for other confounding factors. There were significant seasonal differences in NID (spring, 12.8 ± 6.3%; summer, 12.0 ± 6.1%; fall, 11.7 ± 6.1%; winter, 12.3 ± 5.9%; P = 0.02). However, multivariate analysis revealed that there was no significant association between season and NID after adjustment for other confounding factors (β = -0.012, P = 0.56). There was no significant correlation between NID and daily outdoor mean temperature (r = -0.03, P = 0.17). Multivariate analysis revealed that outdoor temperature was not significantly associated with NID (β = -0.006, P = 0.78). There was no significant association of FMD or NID with season or outdoor temperature, suggesting that it is not necessary to take into account the effects of season and outdoor temperature on vascular function when interpreting the results of FMD and NID measurements. Public trials registry number: UMIN000039512.

(297) Evaluation of Endothelial Function and Metabolic Profile in Patients with Prostate Cancer Undergoing Androgen Deprivation Therapy

Abstract Introduction Androgen deprivation therapy (ADT) has been the cornerstone of prostate cancer treatment. ADT delays cancer progression, alleviates cancer-related symptoms, and is associated with survival gains. Despite these established benefits, the therapy comes with known side effects, such as increased cardiovascular adverse events and metabolic changes. Despite the well-established association between the level of circulating testosterone and endothelial integrity, the direct effects of ADT on endothelial function remain controversial. Objective The aim of the present study was to investigate the impact of ADT on endothelial function, through the analysis of vascular parameters of the brachial artery, and the measurement of serum inflammatory markers. It was also our goal to evaluate early impact of ADT on anthropometric and metabolic parameters Methods We prospectively evaluated men with moderate to high-risk prostate cancer treated with ADT from January to July 2022 at our institution. Patients with decompensated diabetes mellitus (HbA1c &amp;gt;9%), active smokers or smokers who have ceased for less than 5 years and those with confirmed diagnosis of peripheral artery disease, coronary artery disease, angina, congestive heart failure, myocardial infarction, coronary revascularization or stroke, were excluded. Brachial artery assessment included vascular diameter and flow-mediated (endothelium-dependent) vasodilation (FMD) using high-resolution B-mode ultrasound. Our metabolic and inflammatory profile included serum measurement of total cholesterol and fractions, triglycerides, fasting glucose, glycated hemoglobin, basal insulin, C-reactive protein, and bioimpedance assessment of body fat distribution. All measurements were performed at baseline and after 3 months of ADT initiation with goserelin acetate 10.80mg. Results A total of 14 men with mean age of 67.9 ± 6.9 years were included. The prevalence of diabetes in the present cohort was 21.4%. FMD demonstrated a slight increase following ADT, which did not reach statistical significance after 3 months (median 2.2% vs. 5.0%; p = 0.8224 – Figure 1). Baseline brachial artery diameter significantly decreased with ADT compared to baseline (median diameter 0.43cm vs 0.40cm; p = 0.006). With regard to the metabolic profile, ADT significantly increased insulin resistance: fasting insulin levels (mean 9.67 ± 6.09 vs 13.19 ± 7.47; p = 0.002), glycated hemoglobin (mean 5.79% ± 0.47 vs 6.22% ± 0.75; p = 0.009) and homeostatic model assessment insulin resistance increased significantly after 3 months (p = 0.006). Low-density lipoprotein cholesterol (mean 112.00 ± 27.35 vs 128.90 ± 29.00; p = 0.01) and triglycerides (mean 145.40 ± 78.52 vs 168.20 ± 105.80; p = 0.03) concentrations were higher after 3 months of ADT. No significant differences were found in body fat distribution. Conclusions Although the present study has not demonstrated a significant change in brachial artery FMD, we verified an important and surprisingly early worsening of the metabolic profile with ADT, especially increased insulin resistance and dyslipidemia, which represent well-established risk factors for cardiovascular events. Disclosure No

The efficacy of sodium ferulate combination therapy in coronary heart disease: A systematic review and meta-analysis

BackgroundSodium ferulate (SF), a derivative of ferulic acid, is one of the active constituents in medicinal plants thought to be useful in fighting cardiovascular diseases. However, there still lacks a systematic review of the efficacy and safety of SF in treating coronary heart disease (CHD). It is therefore the purpose of this study to comprehensively review all clinical randomized controlled trials (RCTs) of SF in CHD to assess its efficacy and safety. MethodsAll analysis is based on 8 databases as of February 2023, which includes 35 outcomes of RCTs that investigate the effect of SF combination therapy in CHD. The present study evaluates the quality and bias of selected literature by the Jadad scale and Cochrane Collaboration's tools, and also the quality of evidence by GRADE Profiler. Furthermore, it applies sensitivity analysis to assess the high heterogeneity impact of outcomes and conducted subgroup analysis to estimate the influence factors in these studies. The study protocol was set documented, and published beforehand in PROSPERO (Registration No.CRD42022348841). ResultsThe meta-analysis of 36 studies (with 3207 patients) shows that SF combined with conventional drugs has improved clinical effectiveness for patients with CHD [RR: 1.21 (95% CI 1.17,1.26); p < 0.00001]. Statistically significant results of meta-analyses are also seen in electrocardiography (ECG) efficacy, frequency of angina attacks, endothelium-dependent flow-mediated vasodilation (FMD), nitric oxide (NO), endothelin (ET), whole Blood low shear rate (LS), platelet aggregation test (PAgT), C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL6), triglyceride (TG). Adverse events are reported in 6 RCTs. By GRADE approaches, 2 outcomes (clinical efficacy, CRP) indicate a moderate quality of evidence, 17 outcomes indicate low quality of evidence, with the other 16 very low-quality. ConclusionSF combination therapy has a better curative effect than conventional therapy. However, due to items with low-quality evidence demonstrated in the study, the presence of clinical heterogeneity, and imprecision in partial outcome measures, all these led to limitations in the evidence of this study. Thus, the conclusion needs to be further verified by more in-depth research.

Effect of menopause and age on vascular impairment

AimsThe prevalence of cardiovascular diseases increases in women after menopause. The aim of the study was to determine the impact of conventional cardiovascular risk factors such as age, blood pressure, smoking, cholesterol, obesity, and glucose balance, but also menopausal state and sleep-disordered breathing on vascular impairment during menopausal transition. Methods89 women initiated the study and 74 of them participated in the 10-year follow-up. Cardiovascular disease risk factor assessments, ultrasound measurements of brachial artery function, including nitroglycerin-mediated vasodilatation and flow-mediated endothelium-dependent vasodilation, and sleep studies were repeated at baseline and at 5-year and 10-year follow-ups. ResultsOver the study period, all the cardiovascular disease risk estimates increased. Both flow-mediated endothelium-dependent vasodilatation (decline 55 %) and nitroglycerin-mediated vasodilatation (decline 18 %) worsened over the 10 years (p < 0.001). Vascular function was not associated with menopausal state (determined with follicle stimulating hormone). Systolic blood pressure (p = 0.009) and smoking (p = 0.006) at baseline were negatively associated with nitroglycerin-mediated vasodilatation at 5-year follow-up and the use of hormonal therapy at 5-year follow-up was positively associated with concurrent nitroglycerin-mediated vasodilatation (p = 0.041). Intermittent nocturnal hypoxemia at baseline was associated with flow-mediated endothelium-dependent vasodilatation at 10-year follow-up (p = 0.043). High body mass index and impaired glucose balance at 5-year follow-up were associated with nitroglycerin-mediated vasodilatation decline at 10-year follow-up (p = 0.022 and p = 0.037, respectively). ConclusionsWe demonstrate how cardiovascular risk factors and vascular function evolve during menopausal transition. Although menopause was not associated with vascular impairment, short-term improvement in vascular function was observed in those using menopausal hormonal therapy. Intermittent nocturnal hypoxemia, obesity and impaired glucose control are early predictors of vascular decline during postmenopause.

Ranolazine Improves Glycemic Variability and Endothelial Function in Patients with Diabetes and Chronic Coronary Syndromes: Results from an Experimental Study.

Background Ranolazine is a second-line drug for the management of chronic coronary syndromes (CCS). Glucose-lowering and endothelial effects have also been reported with this agent. However, whether ranolazine may improve short-term glycemic variability (GV), strictly related to the prognosis of patients with type 2 diabetes (T2D), is unknown. Thus, we aimed to explore the effects of adding ranolazine to standard anti-ischemic and glucose-lowering therapy on long- and short-term GV as well as on endothelial function and oxidative stress in patients with T2D and CCS. Methods Patients starting ranolazine (n = 16) were evaluated for short-term GV, haemoglobin 1Ac (Hb1Ac) levels, endothelial-dependent flow-mediated vasodilation (FMD), and oxidative stress levels at enrolment and after 3-month follow-up. The same measurements were collected from 16 patients with CCS and T2D that did not receive ranolazine, matched for age, gender, and body mass index. Results A significant decline in Hb1Ac levels was reported after 3-month ranolazine treatment (mean change -0.60%; 2-way ANOVA p = 0.025). Moreover, among patients receiving ranolazine, short-term GV indexes were significantly improved over time compared with baseline (p = 0.001 for time in range; 2-way ANOVA p = 0.010). Conversely, no significant changes were reported in patients without ranolazine. Finally, greater FMD and lower oxidative stress levels were observed in patients on ranolazine at 3 months. Conclusions Ranolazine added to standard anti-ischemic and glucose-lowering therapy demonstrated benefit in improving the glycemic status of patients with T2D and CCS. How this improvement contributes to the overall myocardial benefit of ranolazine requires further studies.

Clinical impacts of endothelium-dependent flow-mediated vasodilation assessment on primary aldosteronism

ObjectivePrimary aldosteronism (PA) is divided into two major subtypes, aldosterone-producing adenoma (APA) and bilateral idiopathic hyperplasia (IHA) and is associated with a higher risk of cardiovascular events. However, the nature of vascular function in PA patients remains to be determined. The aim of this study was to determine the vascular function and investigate the implications of vascular function assessments in the patients.MethodsFlow-mediated dilation (FMD), as an index of endothelial function, and cardio-ankle vascular index (CAVI), as an index of arterial stiffness, were retrospectively compared between 42 patients with APA, 37 patients with IHA, and 42 patients with essential hypertension (EH). These values were also compared with background factors, KCNJ5 mutation and clinical outcome in terms of blood pressure reduction after adrenalectomy in the APA group.ResultsFMD was significantly lower in the APA group (4.8 ± 2.1%) and IHA group (4.1 ± 1.9%) than in the EH group (5.7 ± 2.1%). CAVI did not differ significantly among groups. Although no significant correlations were seen between FMD and background factors in the IHA group, FMD correlated negatively with BMI and plasma aldosterone concentration in the APA group (rs = −0.313, rs = −0.342, respectively). KCNJ5 mutational status was not associated with FMD value. High FMD was associated with blood pressure normalization after adrenalectomy in the APA group.ConclusionsPatients with PA displayed impaired endothelial function. Complete clinical success after adrenalectomy was associated with preserved endothelial function. This study provides a better understanding of FMD assessment in patients with PA.

ПОДАВЛЕНИЕ МАЛОНОВЫМ ДИАЛЬДЕГИДОМ И МЕТИЛГЛИОКСАЛЕМ ЭНДОТЕЛИЙ-ЗАВИСИМОЙ ДИЛАТАЦИИ ПОДВЗДОШНОЙ АРТЕРИИ КРЫС, ВЫЗЫВАЕМОЙ УВЕЛИЧЕНИЕМ КРОВОТОКА

Arterial vessels dilate in response to an increase in blood flow. This regulation is based on the ability of endothelial cells to induce relaxation of vascular smooth muscle cells in response to a rise in wall shear stress. Previously, we demonstrated that dimeric glutaraldehyde (dGA) selectively inhibits endothelium-dependent flow-mediated vasodilation via reinforcing endothelial cell stiffness. The present study aims to find out whether the products of oxidative and carbonyl stress, malonyldialdehyde (MDA) and methylglyoxal (MG), are also able to selectively suppress endothelium-dependent flow-mediated dilation. In experiments on anesthetized rats, the changes in vascular conductance of the intact iliac artery, induced by a stepwise flow rise, were studied under control and after infusion of MDA, MG, or DGA into the arterial bed. Simultaneously, a dilation of the artery in response to intra-arterial injection of ACh was tested before and after exposure of the artery to any of the above aldehydes in order to make sure that endothelium retains its ability to relax smooth muscles. Both MDA and DGA strongly and selectively suppressed the flow-mediated dilation of the iliac artery with virtually no effect on the response to ACh. MG suppressed both arterial responses, with a more profound effect exerted on the flow-mediated dilation and a much lesser effect on the response to ACh. These data suggest that aldehydes produced in the process of lipid peroxidation can lead to endothelial dysfunction. Since the endothelial glycocalyx is referred to as a potential mechanosensor that provides the transduction of wall shear stress into the endothelial cell response, the observed detrimental effects of the tested aldehydes on the ability of the iliac artery to tune its diameter in accordance with blood flow can result from the structural derangement of the endothelial glycocalyx.

Impact of whole body passive heat stress and arterial shear rate modification on radial artery function in young men.

We sought to determine how whole body heating acutely influences radial artery function, characterized using flow-mediated dilation (FMD) and low-flow-mediated constriction (L-FMC), and the mechanistic role of shear rate modification on radial artery functional characteristics during heating. Eleven young healthy men underwent whole body heating (water-perfused suit) sufficient to raise the core temperature by +1°C. Trials were repeated with (heat + WC) and without (heat) the application of a wrist cuff located distal to the radial artery examined, known to prevent increases in mean and anterograde shear rates but increase retrograde shear rate. Radial artery characteristics were assessed throughout each trial, with FMD and L-FMC assessed before and upon reaching the target core temperature. Heat markedly increased radial artery mean and anterograde shear rates, along with radial artery diameter and blood flow (P < 0.05). Heat + WC abolished the heat-induced increase in mean and anterograde shear rates (P > 0.05) but markedly increased retrograde shear rate (P < 0.05). Concomitantly, increases in radial artery diameter and blood flow were decreased (heat + WC vs. heat, P < 0.05). Heat attenuated FMD (8.6 ± 1.2% vs. 2.2 ± 1.4%, P < 0.05), whereas no change in FMD was observed in heat + WC (7.8 ± 1.2% vs. 10.8 ± 1.2%, P > 0.05). In contrast, L-FMC was not different in either trial (P > 0.05). In summary, acute whole body heating markedly elevates radial artery shear rate, diameter, and blood flow and diminishes FMD. However, marked radial artery vasodilation and diminished FMD are absent when these shear rate changes are prevented. Shear rate modifications underpin the radial artery response to acute whole body heat stress, but further endothelium-dependent vasodilation (FMD) is attenuated likely as the vasodilatory range limit is approached.NEW & NOTEWORTHY We observed that acute whole body heating elevates radial artery shear rate, diameter, and blood flow. This results in a diminished flow-meditated dilatation (FMD) but does not change low-flow-mediated constriction (L-FMC). Preventing shear rate changes during whole body heating reduces radial artery vasodilation and reverses FMD reductions but has no effect on L-FMC. These findings indicate that shear rate changes underpin conduit artery responses to acute whole body heat stress, but further endothelium-dependent flow-mediated vasodilation is attenuated as the vasodilatory range limit is approached.

Endothelial dysfunction in patients with myocardial ischemia or infarction and nonobstructive coronary arteries.

The syndromes of myocardial infarction/myocardial ischemia with No Obstructive Coronary Artery Disease (MINOCA/INOCA) are seen more and more often. Endothelial dysfunction (ED) leading to ischemic events has been reported in many of these patients. We aimed to compare patients with MINOCA and INOCA regarding brachial artery flow-mediated endothelium-dependent vasodilation (flow-mediated dilation [FMD]) and plasma concentration of cardiotrophin-1 (CT-1). We included 42 patients with MINOCA and 38 patients with INOCA. Endothelial function was assessed by measuring FMD% and nitroglycerin-mediated dilatation (NMD%) in the brachial artery. The plasma level of CT-1 was determined by solid-phase enzyme-linked immunosorbent assay. FMD% was significantly lower in MINOCA than in INOCA patients (6.45 ± 2.65 vs 8.94 ± 3.32, P < .001), without significant difference in NMD% (10.69 ± 3.19 vs 12.16 ± 3.69, P = .06). Plasma CT-1 levels were not significantly different: 40.1 pg/mL (22.5-102.1) vs 37.2 pg/mL (23.5-67.2), P = .53. Our results suggest worse ED in MINOCA than in INOCA patients, but demonstrated no difference in CT-1 levels between patients with stable and unstable ischemic heart disease and normal coronary arteries.

Seasonal variations on endothelium-dependent flow-mediated vasodilation in adults with type 2 diabetes and nondiabetic adults with hypertension and/or dyslipidaemia who perform regular exercise.

IntroductionEndothelium‐dependent flow‐mediated dilation (FMD) of the brachial artery often changes seasonally. We aimed to examine the association between the seasonal variation on FMD and regular exercise in adults with type 2 diabetes (T2D) and nondiabetic adults with hypertension and/or dyslipidaemia (non‐T2D).MethodsThis retrospective study included 14 T2D and 17 non‐T2D adults, who started to perform moderate‐intensity aerobic exercise for 30‐40 min/d at a hospital gym in 2006‐2010 and maintained exercise performance at least 2 d/wk until the end of the observation period. We observed and analysed the data for 5 years (from March 2011 to February 2016). FMD, cardio‐ankle vascular index (CAVI) and metabolic outcomes were compared among seasons in the T2D and non‐T2D groups.ResultsThe FMD values were lower in winter than in other seasons in both groups (all P < .01). The annual range of FMD was larger by 31% in the T2D group than in the non‐T2D group (P < .05). The systolic blood pressure (BP) values were higher in winter than in other seasons in both groups (all P < .01), and the diastolic BP values were higher in winter than in summer in both groups (T2D: P < .05; non‐T2D: P < .01). CAVI and other outcomes did not change seasonally.ConclusionsFlow‐mediated vasodilation showed seasonal variation in T2D adults, even if they performed exercise regularly for a long period of time. Additionally, we found that the annual range of FMD might increase with the presence of T2D.

Correlations of carotid intima-media thickness with endothelial function and atherosclerosis degree in patients with type 2 diabetes mellitus.

To investigate the correlation of carotid intima-media thickness (IMT) with endothelial function and atherosclerosis degree in patients with type 2 diabetes mellitus. A total of 80 patients with type 2 diabetes mellitus admitted and treated in our hospital from January 2017 to January 2018 were selected and randomly divided into two groups (n = 40). Patients who were definitely diagnosed with type 2 diabetes mellitus were selected as observation group, and individuals who received health examination and were excluded from type 2 diabetes mellitus were enrolled as control group. The diagnosed proportions of carotid plaque, Crouse scores, endothelial-dependent flow-mediated vasodilation (FMD) function and nitroglycerin-mediated dilation (NMD) function of the brachial arteries in the two groups were compared. The indexes related to vascular endothelial functions [vascular endothelial growth factor (VEGF), endothelin-1 (ET-1) and nitric oxide (NO) levels] in the two groups were detected. The correlations of Crouse score with brachial arterial FMD value, VEGF level, ET-1 level and NO level in observation group were analyzed. The diagnosed proportion of carotid plaque in observation group was significantly higher than that in control group (P < 0.05), and the Crouse score in observation group was higher than that in control group (P < 0.05). The brachial arterial FMD value in observation group was remarkably lower than that in control group (P < 0.05). Compared with control group, VEGF and ET-1 levels were significantly reduced in observation group (P < 0.05), with the statistical increase of NO level (P < 0.05). In observation group, the Crouse score was negatively correlated with the brachial arterial FMD value, VEGF level and ET-1 level, whereas positively correlated with the NO level (P < 0.05). Our data show that the carotid IMT is increased significantly among patients with type 2 diabetes mellitus, and the vascular endothelial function is impaired. Moreover, after the occurrence of atherosclerosis, we found the carotid IMT is negatively correlated with endothelial-dependent FMD, as well as levels of VEGF and ET-1, whereas shows positive correlation with the vasodilative factor NO.

Short-Term Water- and Land-Based Exercise Training Comparably Improve Exercise Capacity and Vascular Function in Patients After a Recent Coronary Event: A Pilot Randomized Controlled Trial.

BackgroundWe hypothesized that a 2-week twice daily aquatic endurance plus calisthenics exercise training program: (i) increases aerobic exercise capacity (peak oxygen uptake/O2peak), (ii) improves endothelium-dependent flow-mediated vasodilation (FMD), and (iii) reduces circulating markers of low-grade inflammation and hemostasis, as compared to land-based endurance plus calisthenics exercise training or no exercise in patients undergoing short-term residential cardiac rehabilitation after a recent coronary artery disease (CAD) event.MethodsPatients with a recent myocardial infarction or revascularization procedure were randomized into two interventional groups and a control group. The interventional groups underwent supervised aerobic endurance plus calisthenics exercise training either in thermo-neutral water or on land at moderate intensity (60–80% of the peak heart rate achieved during symptom-limited graded exercise testing) for 30 min twice daily for 2 weeks (i.e., 24 sessions). The control group was deferred from supervised exercise training for the 2-week duration of the intervention, but was advised low-to-moderate intensity physical activity at home while waiting. At baseline and after the intervention period, all participants underwent estimation of aerobic exercise capacity, brachial artery flow-mediated dilatation (FMD, measured ultrasonographically at rest and during reactive hyperemia after 4.5 min of forearm cuff inflation), markers of cardiac dysfunction (NT-proBNP), inflammation (hsCRP, IL-6, IL-8, IL-10), cell adhesion (ICAM, P-selectin), and hemostasis (fibrinogen, D-dimer).ResultsA total of 89 patients (mean age 59.9 ± 8.2 years, 77.5% males, O2peak at baseline 14.8 ± 3.5 ml kg-1 min-1) completed the study. Both exercise modalities were safe (no significant adverse events recorded) and associated with a significant improvement in O2peak as compared to controls: age and baseline O2peak-adjusted end-of-study O2peak increased to 16.7 (95% CI 16.0–17.4) ml kg-1 min-1 with land-based training (p < 0.001 for change from baseline) and to 18.6 (95% CI 17.9–19.3) ml kg-1 min-1 with water-based training (p < 0.001 for change from baseline), but not in controls (14.9 ml kg-1 min-1; 95% CI 14.2–15.6; p = 0.775 for change from baseline). FMD also increased in both intervention groups (from 5.5 to 8.8%, p < 0.001 with land-based, and from 7.2 to 9.2%, p < 0.001 with water-based training, respectively), as compared to controls (p for change 0.629). No significant changes were detected in biomarkers of inflammation, cell adhesion or hemostasis, whereas levels of NT-proBNP (marker of cardiac dysfunction) decreased in the water-based training group (p = 0.07 vs. controls).ConclusionEndurance plus calisthenics exercise training in thermo-neutral water is safe, and improves aerobic exercise capacity and vascular function in patients undergoing short-term residential cardiac rehabilitation after a recent CAD event.Clinical Trial Registrationwww.ClinicalTrials.gov, identifier NCT02831829.

Significance of the pulsatility index in the evaluation of hemodynamic changes in peripheral arterial circulation in the obese treated with orlistat

Background/Aim. Prolonged hyperinsulinemia accelerates the process of endothelial dysfunction and arteriosclerotic changes affecting the development of cardiovascular and cerebrovascular diseases. There are various measuring techniques for the evaluation of early functional changes in the arterial wall such as: flow-mediated endothelium-dependent vasodilation, impulse wave analysis, intima-media thickness assessment, venous plethysmography and so on; however, each has certain limitations in results interpretation. The aim of this study was to indicate the association of the pulsatility index (PI) that shows peripheral arterial contractility, with the changes in metabolic parameters under insulin resistance conditions. Methods. The study included a total of 30 healthy obese subjects with the values of body mass index more than 30 kg/m2, randomized with double blind design into two groups: placebo and orlistat. The extent of insulin sensitivity was calculated on the basis of glycemia and insulinemia values using an appropriate formula. Results. The obtained results suggest a statistically significant improvement in the PI index in the orlistat group (p &lt; 0.002), while there was no such improvement in the placebo group. Conclusion. The results obtained in this study indicate the improvement in insulin sensitivity within early arteriosclerosis is a significantly favorable effect of orlistat on peripheral arterial circulation additionally supported by the reduction in levels of lipid fractions, especially triglycerides. Early hemodynamic changes under conditions of the reduced insulin resistance are characterized by the increase in arterial wall contractility evaluated by the PI determination.

Correlation analysis of age with endothelial function and oxidative stress in the healthy population

Objective To evaluate the vascular endothelial function and oxidative stress level in the healthy population, and to provide evidence for preliminary nursing care regarding abnormal endothelial function in healthy people. Methods A total of 296 healthy people who had physical examination in Beijing Hospital from March to October 2016 were selected in this study using convenience sampling. The participants were divided into the youth group (30-44 years old) , middle-aged group (45-59 years old) and elderly group (60-79 years old) . The routine biochemical indexes, blood nitric oxide (NO) , blood endothelin (ET-1) , blood malondialdehyde (MDA) , blood superoxide dismutase (SOD) , and brachial artery flow mediated endothelium dependent vasodilatation function (FMEDD) were measured for the participants. Results There were significant differences in FMEDD, NO and SOD among different age groups (P<0.05) . The age was negatively correlated with fasting FMEDD, NO and SOD (r=-0.767 8, -0.465 2, -0.625 0; P<0.05) . However, a positive correlation was found between age and ET-1 and MDA (r= 0.112 6, 0.095 7; P<0.05) . Conclusions The vascular endothelial function and antioxidant stress index decrease with age in the healthy population. The decline of vascular endothelial function in the elderly over 60 years old should be concerned. The elderly people should strictly control their blood pressure, blood glucose, blood lipid and other risk factors for vascular endothelial function to prevent endothelial dysfunction in the early stage, especially in people who have no history of hypertension, diabetes, or hyperlipidemia. Key words: Age groups; Vascular endothelial function; Oxidative stress

Arterial endothelial dysfunction in stable COPD patients and the correlation between the degree of endothelial dysfunction and the severity of COPD

Objective To investigate arterial endothelial dysfunction in stable chronic obstructive pulmonary disease (COPD) patients and the correlation between the degree of endothelial dysfunction and the severity of COPD. Methods Forty stable COPD patients were enrolled in a COPD group and 30 non-COPD individuals in a control group.The endothelium-dependent flow-mediated vasodilatation (FMD) of the brachial artery and serum eNO value were measured in both groups.Forced expiratory volume in 1 second (FEV1)/prediction of FEV1 was determined and expressed as FEV1 (% pred). Results The mean FMD was significantly lower in the COPD group (11.21±5.19)% than in the control group (19.86±5.24)%(t=6.090, P=0.001). The Pearson’s correlation analysis showed FMD was positively correlated with FEV1 (%pred) in COPD patients (r=0.440, P<0.05). The mean serum eNO level in the COPD group (108.58±42.22)μmol/L was significantly lower than in the control group (151.17±97.40)μmol/L (t=2.242, P=0.039). Conclusions The endothelium-dependent flow-mediated vasodilatation is significantly impaired in stable COPD patients, and the degree of impairment is proportional to the FEV1 (% prediction of FEV1) in COPD patients. Key words: Vascular endothelium; Pulmonary disease, chronic obstructive; Nitric oxide

The relationship between number and function of EPCs and concentration of VEGF165 and SDF-1 in coronary artery spasm.

We aimed at investigating the functions of endothelial progenitor cells (EPCs) in the pathophysiology of coronary artery spasm (CAS) and coronary artery disease (CAD), as well as to evaluate the correlation of these diseases with the number and function of EPCs, the plasma concentration of vascular endothelial growth factor 165 (VEGF165) and stromal cell-derived factor 1 (SDF-1). Participants were recruited into three groups, CAS, CAD and the control. The number and functions of early EPCs and outgrowth endothelial cells (OECs) were determined in peripheral blood samples, and the endothelial function was evaluated by measuring endothelium-dependent flow-mediated vasodilation (FMD). No differences of baseline characteristics were found among CAS, CAD, and the control groups. The OECs isolated from CAS and CAD exhibited significant decrease in the percentage of CD34+/CD45- population, OEC colony formation, OEC proliferation and OEC tubulogenesis, nitric oxide (NO) production, endothelial nitric oxide synthase (eNOS) activity, and the phosphorylation level at Ser1177 of eNOS, compared with OECs isolated from control participants. Meanwhile, FMD was significantly reduced in CAS and CAD (CAS, 4.1% ± 1.9%; CAD, 4.3% ± 1.8%; control, 11.2% ± 3.5%). FMD was positively correlated to OEC functions including NO production, eNOS phosphorylation, colony formation, and proliferation. No differences of plasma VEGF165 and SDF-1 concentrations were recorded among these three groups. Similarly, there was no correlation between plasma VEGF165 (and SDF-1) concentration and EPC number and function. EPCs show the potential of repairing damaged endothelium in CAS and CAD.

Vitamin D receptor activation raises soluble thrombomodulin levels in chronic kidney disease patients: a double blind, randomized trial.

Thrombomodulin (TM) is a proteoglycan highly represented in the endothelial glycocalix that regulates the haemostasis and the endothelial response to inflammation. High soluble TM levels underlie a lower risk for coronary heart disease in population studies. Activation of vitamin D receptor (VDR) upregulates TM, but the effect of this intervention on soluble TM has never been tested in chronic kidney disease (CKD) patients. We performed a post hoc analysis of a 12 weeks double blind, randomized, placebo-controlled trial testing the effect of VDR activation by paricalcitol (PCT) on endothelium-dependent flow-mediated vasodilatation (FMD) in the forearm (ClinicalTrials.gov identifier: NCT01680198). Circulating TM was measured in the whole CKD population [88 patients: PCT n = 44; placebo n = 44] that took part into this trial. Soluble TM at baseline was inversely related to the glomerular filtration rate (r = -0.65, P < 0.001) and to FMD (Spearman's ρ = -0.29, P = 0.01). Alongside the expected effects on bone mineral biomarkers, PCT produced a consistent rise (P = 0.005) in TM levels, from a median value of 8446.0 pg/mL [interquartile range (IQR): 6227.8-10 910.8 pg/mL] to 9127.5 pg/mL (6393.0-11 287.3 pg/mL) while placebo had no effect (between-groups difference P = 0.008). TM levels re-approached baseline values 2 weeks after stopping PCT. TM changes across the trial paralleled simultaneous changes in FMD. VDR activation by PCT raises TM levels and FMD and such effects are rapidly reversible after stopping the treatment. The TM rise induced by PCT is a possible mechanism whereby improvement in endothelial function by VDR activation may favourably impact upon vascular health in CKD patients.

Effects of hyperbaric oxygen on vascular endothelial function in patients with slow coronary flow

To improve therapy for slow coronary flow (SCF), the effects of hyperbaric oxygen (HBO) therapy on vascular endothelial function in SCF patients is the focus of this investigation. Ninety-eight patients who exhibited chest discomfort were retrospectively analyzed, and di-agnosed with SCF by coronary artery angiography at the Third Hospital of Hebei Medical University, Shijiazhuang, China from 2014 to 2016. The patients were divided into two groups according to the following treatment: HBO group (n = 48) and the control group (n = 50). Patients in the control group were administrated with conventional treatment, while those in the HBO group were administrated HBO therapy for 4 weeks in addition to conventional treatment. To evaluate the effects of HBO on vas-cular endothelial functions, plasma levels of nitric oxide (NO), calcitonin gene-related peptide (CGRP), endothelin-1 (ET-1), high sensitivity C-reactive protein (hsCRP) as well as endothelial-dependent flow-mediated vasodilation (FMD) of the brachial artery were measured in both groups before and after their respective treatments. There were no significant differences in plasma levels of NO, ET-1, CGRP, hsCRP nor in FMD measurements between the two groups before treatment (p > 0.05). Moreover, the levels of all the parameters measured showed no significant changes before and after treatment in the control group. However, when comparing the control group, FMD and plasma NO and CGRP levels were significantly increased in the HBO group after treatment (p < 0.01), whereas hsCRP and ET-1 levels decreased dramatically (p < 0.001). The HBO treatment in addition to conventional therapy may significantly improve the vascular endothelial function in SCF patients. (Cardiol J 2018; 25, 1: 106-112).