Flow-mediated Dilation Levels Research Articles

Endothelial dysfunction in prediabetes and diabetes mellitus in patients with normal coronary arteries

BackgroundDiabetes mellitus (DM) is a global health issue associated with increased cardiovascular disease risk. Endothelial dysfunction is a known precursor to atherosclerosis and cardiovascular disease, and its role in the pathogenesis of DM complications is well-documented. There is limited information in the evaluation of endothelial function in prediabetic patients using flow-mediated dilation (FMD), and studies have not excluded patients with known atherosclerosis or coronary artery disease. Thus, in this study, we aimed to evaluate the endothelial functions using FMD from the brachial artery of DM and prediabetes patients who had normal coronary arteries.MethodsThis study included 73 participants: 25 with DM, 25 with prediabetes, and 23 normoglycemic controls, all with normal coronary arteries on angiography. FMD measurements were conducted following established protocols, and statistical analysis was performed using standard methods to compare FMD levels among groups.ResultsThe groups were comparable in clinical and demographic characteristics, except for fasting plasma glucose levels. Significant differences in FMD levels were observed: 10.1% in the DM group, 16.5% in the prediabetes group, and 14.8% in the control group (P = 0.004). Diabetic patients had significantly lower FMD levels than both prediabetic and normoglycemic individuals. No significant difference in FMD was found between prediabetic and control groups.ConclusionsDiabetic patients exhibited significant endothelial dysfunction compared to normoglycemic individuals, while prediabetic patients did not show similar dysfunction. These findings suggest a window of opportunity in the prediabetic stage for early intervention to prevent advanced endothelial dysfunction.Trial registration numberISRCTN Registry ISRCTN15351014. Registry date: 23/09/2024. Retrospectively registered.

Effects of SGLT-2i and GLP-1RA in vascular function parameters: the impact of the weight loss

Abstract Background Arterial stiffness and endothelial function markers flag increased cardiovascular disease risk in patients with type 2 Diabetes Mellitus (T2DM), while weight management plays a crucial role for the management of glycemic control and prevention of complications in these patients. Purpose To investigate the effects of novel antidiabetic agents on arterial stiffness and endothelial function as well as the metabolic parameters of HbA1c and Weight in T2DM patients. Patients and Methods: We enrolled 99 consecutive patients under stable antidiabetic therapy who did not reach therapeutic targets. Subjects were assessed to receive an additional antidiabetic agent to optimize glucose control; glucagon like peptide-1 receptor agonist (GLP-1RA, n=50) or sodium/glucose cotransporter-2 inhibitor (SGLT-2i, n=49). Glycosylated hemoglobin (Hba1c) and weight expressed through Body Mass Index (BMI) along with carotid-femoral pulse wave velocity (PWV) and flow-mediated dilatation (FMD), as biomarkers of arterial stiffness and endothelial function accordingly, were measured at baseline and 3 months after treatment intensification. Results There were no differences between the study groups in traditional risk factors of age and sex or baseline HbA1c, BMI, PWV, and FMD levels (ps=NS for all). In both groups PWV values displayed a statistically significant improvement from 11.2±2.5 to 9.3±2.2 m/sec (p<0.001) in the GLP-1RA group and from 10.7±2.4 to 8.9±2.0 m/sec (p=0.001) in the SGLT-2i group, as presented in Figure 1 through the differences in the values of PWV. FMD values were also significantly improve in both groups from baseline to follow-up; from 6.04±1.22 to 6.50±1.26% (p<0,001) for the GLP-1RA group and from 6.38±1.21 to 6.81±1.29% (p<0.001) for the SGLT-2i group. Moreover, both groups achieved better weight management goals in terms of BMI values between baseline and follow-up; from 33.6±4.9 to 31.5±4.6 kg/m2 for the GLP-1RA group (p<0.001) and from 31.8±5.5 to 30.5±5.6 kg/m2 for the SGLT-2i group (p<0.001), in addition to achieving better glycemic control in terms of HbA1c values, as seen in their paired differences: for GLP-1RA: 1.3±0.7% and for SGLT-2i: 0.8±0.5%. Interestingly, in the SGLT-2i group the magnitude of the PWV improvement was correlated with the weight loss (r=0.368, p=0.007). Conclusion These data provide evidence that the newer antidiabetic drugs, both GLP1-RA and SGLT-2i, have actions that benefit both vascular function, endothelium as well as metabolic parameters. Interestingly, in the patients receiving SGLT-2i the magnitude of the PWV improvement was correlated with the weight loss.delta PWV for SGLT-2i & GLP-1RA groupsCorrelation of deltaWeight & deltaPWV

The effect of periodontal treatments on endothelial function in degrees of periodontitis patients: A systematic review and meta-analysis.

This article focus on patients with moderate-to-severe periodontitis and periodontitis patients with cardiovascular disease. After they received periodontal initial therapy or antimicrobial drug treatment, was there any improvement in endothelial function during short- and long-term followups? Relevant randomized controlled trials and clinical trials up to 30th June 2024 were identified and retrieved from electronic databases including PubMed, Cochrane Library, Web of Science and CNKI databases, with periodontitis therapy, periodontal disease and endothelial function as the keywords. The weighted (WMD) or standardized mean difference (SMD) was calculated using a fixed- or random-effect model and assessed heterogeneous results. Generally, 14 studies published between 2004 and 2022 were eligible for the meta-analysis, which are all randomised clinical trials. A total of 491 periodontitis patients were screened. All participants received whole-mouth supragingival and subgingival scaling and root planing of the teeth, some trials combined with antimicrobial drug treatment as well as extracting teeth that could not be saved. The outcome indicators were measured by flow-mediated dilatation(FMD) levels. The results of the short term (≤3 months) periodontitis initial therapy group showed positive results (WMD = -3.78,95%CI = [-5.49,-2.07], P<0.0001), while the results of the long term (6 months) periodontitis therapy group exhibited significant difference (WMD = -0.96,95%CI = [-2.06,0.14],P = 0.09). Furthermore, study population were categorized according to the severity of periodontitis, the presence of comorbidities, endothelial dysfunction, and the inclusion of extractions and antimicrobial therapy in the treatment process. The effects of each of these factors on FMD were explored and the results of these subgroups all support periodontitis therapy. The results showed that periodontal treatment enhances endothelial function. Additionally, after subgroup analysis of long-term and short-term follow-up, patients with severe periodontitis, and different periodontal treatments, periodontal therapy was shown to increase FMD levels.

T-cell senescence was correlated with early atherosclerosis inpatients with systemic lupus erythematosus.

To investigate the correlation between T-cell senescence with the atherosclerosis markers in patients with systemic lupus erythematosus (SLE). The study participants were 40 female SLE patients aged 18-45 years who met the 2019 EULAR/ACR criteria and 40 healthy individuals. The atherosclerosis markers were investigated using the Doppler ultrasonography examinations to measure the cIMT (carotid intima-media thickness) and flow-mediated dilation (FMD) and serological markers using soluble ICAM-1 and VCAM-1. Flow cytometry of CD4+CD57+, CD8+CD57+, CD4+CD28null, and CD8+CD28null T cells were used to assess the immunosenescence markers. The cIMT (p < .001), sICAM-1 (p < .001), and sVCAM-1 (p < .001) were significantly higher in SLE patients compared with control, while FMD was significantly lower in SLE patients (p < .001). The percentages of all T-cell senescence markers are also significantly higher in SLE patients than in healthy individuals. Positive correlations were shown between cIMT with the CD4+CD57+ (R = .301, p = .005), CD4+CD28null (R = .448, p < .001), and CD8+CD28null (R = .422, p < .001). Conversely, negative correlations were demonstrated between the FMD with CD4+CD57+ (R = -.236, p = .023), CD8+CD57+ (R = -.409, p < .001), CD4+CD28null (R = -.422, p < .001), and CD8+CD28null (R = -.318, p = .003). The soluble markers of sICAM-1 and sVCAM-1 were also positively correlated with the T-cell senescence markers. Early sign of atherosclerosis was demonstrated in patients with SLE in this study. T-cell senescence markers had significant correlations with the atherosclerosis markers, including the cIMT, FMD, and soluble adhesion molecules levels. Understanding the link between immunosenescence and atherosclerosis might help to identify a new method for early detection and treatment of atherosclerosis in SLE.

Evaluating the impact of short-term nitrate-rich dietary supplementation on endothelial function in COPD: A randomized crossover study

AimThis study aimed to investigate the acute effects of dietary nitrate ingestion through l-arginine supplementation or dehydrated beet consumption on endothelial function in chronic obstructive pulmonary disease (COPD) patients. The secondary outcome was to analyze arterial stiffness, plasma nitrate, and nitrate/protein concentration. MethodsIn this randomized crossover study, subjects with COPD underwent three series of supplementation: (1) l-arginine, (2) dehydrated beetroot, and (3) a placebo that appeared like the other supplements. Each intervention lasted 14 days, with a 7-day washout period between series. Participants underwent endothelial function assessment using flow-mediated dilatation (FMD), and plasma nitrate levels were measured at the end of each supplementation series. ResultsSeventeen subjects (twelve male) completed the study protocol. Only five subjects presented endothelial dysfunction (RHI ≤0.51) at baseline. The mean baseline characteristics included age 66.5 ± 9.4 years, BMI 27.5 ± 4.5 kg/m2, FEV1, 0.79 (0.67–1.06) L. There were no differences (p > 0.05) between the groups or from pre-to post-interventions for RHI and arterial stiffness index (AIx) values, as well as parameters of endothelium-dependent vasodilation, such as blood flow velocity (BFV), shear stress, shear rate, FMD (mm), and FMD%. There was also no differences (p > 0.05) between the groups or from pre-to post-interventions plasma nitrate levels. ConclusionsAcute dietary supplementation with nitrates, at the doses provided, did not show a significant improvement in endothelial function assessed by FMD, EndoPAT, or plasma nitrate levels in COPD. These findings suggest that a higher dose or prolonged supplementation might be required to achieve a therapeutic effect.

Temporal Convolutional Neural Network-Based Prediction of Vascular Health in Elderly Women Using Photoplethysmography-Derived Pulse Wave during Exercise.

(1) Background: The objective of this study was to predict the vascular health status of elderly women during exercise using pulse wave data and Temporal Convolutional Neural Networks (TCN); (2) Methods: A total of 492 healthy elderly women aged 60-75 years were recruited for the study. The study utilized a cross-sectional design. Vascular endothelial function was assessed non-invasively using Flow-Mediated Dilation (FMD). Pulse wave characteristics were quantified using photoplethysmography (PPG) sensors, and motion-induced noise in the PPG signals was mitigated through the application of a recursive least squares (RLS) adaptive filtering algorithm. A fixed-load cycling exercise protocol was employed. A TCN was constructed to classify flow-mediated dilation (FMD) into "optimal", "impaired", and "at risk" levels; (3) Results: TCN achieved an average accuracy of 79.3%, 84.8%, and 83.2% in predicting FMD at the "optimal", "impaired", and "at risk" levels, respectively. The results of the analysis of variance (ANOVA) comparison demonstrated that the accuracy of the TCN in predicting FMD at the impaired and at-risk levels was significantly higher than that of Long Short-Term Memory (LSTM) networks and Random Forest algorithms; (4) Conclusions: The use of pulse wave data during exercise combined with the TCN for predicting the vascular health status of elderly women demonstrated high accuracy, particularly in predicting impaired and at-risk FMD levels. This indicates that the integration of exercise pulse wave data with TCN can serve as an effective tool for the assessment and monitoring of the vascular health of elderly women.

The Association of Systemic Endothelial Dysfunction With Diffuse Diabetic Macular Edema.

Our aim was to assess whether systemic endothelial dysfunction, evaluated non-invasively by flow mediated dilation (FMD), is associated with diabetic macular edema (DME) and to determine if it is further impaired in patients with diffuse-DME. Consecutive patients (n = 84) with type-2 diabetes mellitus (T2DM) and diabetic retinopathy were enrolled. DME was not present in 38 (non-DME) and present in 46 patients; 25 with focal and 21 with diffuse-DME. No differences were detected between DME and non-DME groups regarding the clinical and demographic characteristics, except for the age of T2DM initiation (lower in non-DME). FMD values were significantly impaired in DME compared with non-DME patients, even after adjustment for multiple covariates (3.56 ± 1.03 vs 4.57 ± 1.25%, P = .003). Among DME patients, no differences were found concerning the clinical and demographic data, while FMD levels were significantly lower in diffuse-DME patients, compared with the focal-DME ones, regardless of the impact several confounders (2.88 ± 0.65 vs 4.08 ± 0.95%, P = .002). It is noteworthy that FMD values of non-DME and focal-DME patients did not differ significantly (4.52 ± 1.24 vs 4.21 ± 1.06%, P = .307). Moreover, among DME patients, impaired FMD was an independent predictor of diffuse-DME (odds ratio: 0.06, 95% CI 0.01-0.47, P = .007).

Endothelial Function Correlates With Pulmonary Pressures in Subjects With Clinically Suspected Pulmonary Hypertension

BackgroundImpaired pulmonary circulation hemodynamics are characteristic of pulmonary hypertension. We therefore sought to evaluate possible correlations between endothelial function non-invasively assessed by flow-mediated dilation (FMD) and hemodynamic parameters at right heart catheterization (RHC) in patients with clinically suspected pulmonary hypertension. MethodsConsecutive outpatients with suspected PH were enrolled in the study. In all patients, endothelial function was assessed by FMD and hemodynamic parameters (pulmonary artery pressure (PAP), pulmonary vascular resistances (PVR)) were derived by RHC. ResultsNinety-five consecutive patients with suspected pulmonary hypertension were enrolled in the study (mean age 63±13 years, 58% male) and included in the analysis. FMD values were significantly correlated with systolic (s)PAP levels (r=-0.29, P=0.016); correlation with pulmonary vascular resistance values was of borderline significance (r=-0.21, p=0.78).After multivariable regression analysis including age, gender, TAPSE and peak tricuspid regurgitation velocity (peak-TVR), and FMD, the latter remained significantly correlated with sPAP values (B=-47, p=0.02). After classifying patients according to median levels of peak TRV and FMD into 3 groups (neither, either, or both impaired), progressively increased levels of sPAP, mPAP and PVR were found (P for trend <0.001 in all cases). ConclusionsFMD values were inversely related with sPAP levels in a small population of patients with clinically suspected PH. In combination with peak TRV levels, FMD values non-invasively assessed were predictive of increased sPAP, mPAP, and PVR.

Correlation Between Serum microRNA-18a Level and Endothelial Function and Prognosis in Female Coronary Heart Disease Patients.

The aim was to analyze the correlation between serum microRNA (miR)-18a level, endothelial function, and prognosis in female coronary heart disease (CHD) patients. One hundred sixtyfemale patients admitted to our hospital for the first occurrences of chest pain and tightness were divided into CHD and non-CHD groups based on the coronary angiography results. Clinical data, laboratory indexes, serum miR-18a level, and endothelial function [flow-mediated dilation (FMD) function, endothelin 1 (ET-1), and nitric oxide (NO)] were compared. There were no significant differences in clinical data (except CHD family history) between 2 groups. Coronary heart disease group had significantly lower levels of NO and FMD, while significantly higher levels of miR-18a and ET-1 than non-CHD group (P <.05). Pearson correlation showed that serum miR-18a level was positively correlated with ET-1 (r = 0.492, P <.001), and negatively correlated with NO and FMD (r = -0.504, -0.307, P <.001). The receiver operating characteristic) curve showed that the area under the curve of serum miR-18a level in predicting the occurrence of CHD in women was 0.878 (95% CI: 0.828-0.928). Compared with good prognosis group, poor prognosis group had signifi-cantly lower NO, and FMD levels, while higher proportions of acute coronary syndrome, multivessel disease, miR-18a, and ET-1 levels (P <.05). The expression of serum miR-18a in female CHD patients was high, which was related to endothelial function. The increase in serum miR-18a level was a risk factor for the occurrence of MACE in female CHD patients during follow-up, and the serum miR-18a level could effectively predict the occurrence of CHD in female patients.

Abstract 14589: Impairment of Endothelial Function by Chronic Cannabis Use: An Interim Analysis of the CANDIDE Study

Background: Increasing cannabis legalization has led to a surge in cannabis use. To understand the consequences for cardiovascular health, we have initiated the CANnabis: Does It Damage Endothelium (CANDIDE) study. Here, we report results of an interim analysis. Aims: To investigate the effects of chronic cannabis product use on endothelial function. Approach: We recruited 44 healthy non-tobacco smokers/vapers, 21-50 yrs, in 3 groups based on chronic cannabis use: cannabis smokers, THC edible users, and nonusers. Participants underwent assessment of brachial artery flow-mediated dilation (FMD) and carotid-femoral pulse wave velocity (PWV). Human umbilical vein endothelial cells (ECs) were exposed to sera from each individual with and without VEGF to determine serum effects on endothelial NO production. Human lung microvascular ECs were also exposed to the individual sera and cell permeability was measured by electric cell-substrate impedance sensing. Results: FMD and VEGF-stimulated NO levels were both significantly lower in cannabis smokers than nonusers (5.7±3.3% vs 12.0±8.0%, p=.037, and 1.1±0.3 nM vs 1.5±0.3 nM, p=.018, respectively; figure), comparable effects to what we have reported for tobacco smokers. In contrast, FMD, but not VEGF-stimulated NO levels, was lower in the THC edible users than nonusers (5.0±4.1% vs 12.0±8.0%, p=.031, and 1.6±0.3 nM vs 1.5±0.3 nM, p=.54). There were no significant differences in other functional properties (p&gt;.48). CD31 and IL-1β, which are circulating inflammatory biomarkers that we showed are elevated in tobacco smokers, were not elevated in cannabis smokers. The inflammatory biomarker PTX3 was lower in cannabis smokers than nonusers (p=.038). Conclusion: Chronic cannabis use impairs endothelial function but may reduce inflammation. Our findings suggest that the impairment caused by smoking cannabis vs edible THC use occurs via distinct mechanisms differing in the involvement of endothelial NO production.

Influence of enhanced external counterpulsation on endothelial function: a meta-analysis of randomized controlled trials

Objectives Enhanced external counterpulsation (EECP) is an effective and noninvasive treatment for patients with refractory angina and chronic heart failure. However, previous studies evaluating the influence of EECP on endothelial function showed inconsistent results. This systematic review and meta-analysis was conducted to evaluate the effects of EECP on endothelial function measured by brachial artery flow-mediated dilation (FMD). Design PubMed, Embase, Cochrane Library, CNKI, and Wanfang databases were searched for randomized controlled trials comparing the influence of EECP versus usual care on FMD in adult population. A random-effects model incorporating the potential influence of heterogeneity was used to pool the results. Results Nineteen studies with 1647 patients were included in the meta-analysis. Compared with usual care or conventional therapy, additional treatment with EECP for 3–7 weeks was associated with a significantly improved FMD (mean difference [MD]: 1.96%, 95% confidence interval [CI]: 1.57–2.36, p < 0.001, I 2 = 52%). Subgroup analysis showed consistent results in patients with coronary artery disease and in patients with other diseases (p for subgroup difference = 0.21). Results of meta-regression analysis showed that the mean baseline FMD level was positively correlated with the influence of EECP on FMD (coefficient = 0.42, p < 0.001). Results of subgroup analysis suggested that the increment of FMD following EECP was larger in patients with baseline FMD ≥ 5% (MD: 2.69, 95% CI: 2.27–3.10, p < 0.001; I 2 = 15%) compared to those with baseline FMD < 5% (MD: 1.49, 95% CI: 1.13–1.85, p < 0.001; I 2 = 0%; p for subgroup difference < 0.001). Conclusions EECP may be effective in improving endothelial function measured by FMD.

P-336 Presence of stage III/IV endometriosis associated with systemic inflammation poses as individual risk factor for coronary heart disease in Indian women: Inklings for the search

Abstract Study question Can investigating endometriosis—cardiovascular interaction identify women with stage III/IV endometriosis and elucidate pathophysiology of the female heart at a broader level? Summary answer Endothelial dysfunction can occur in absence of structural atherosclerotic changes in young Indian women with endometriosis urging lifelong multidisciplinary care to manage long-term health impact. What is known already Chronic inflammation, enhanced oxidative stress, endothelial dysfunction, and cellular proliferation are hallmarks of both atherosclerosis and endometriosis with unveiled cellular and molecular overlaps between the duos. Further, treatment/s of endometriosis, like, hysterectomy or oophorectomy and/or analgesics confer increased risk of coronary heart disease (CHD) to women with endometriosis. However, CHD in women with endometriosis remains understudied, under-recognized, and underdiagnosed. Incidentally, early atherosclerosis cannot be explained exclusively by traditional cardiovascular risk factors. Aim of the present study was to correlate subclinical atherosclerosis with metabolic parameters and markers of endothelial inflammation in Indian women with stage III/IV endometriosis. Study design, size, duration This observational prospective cohort study constituted 1407 consented women diagnosed with laparoscopically confirmed endometriosis (Group A; n = 718) with age matched control (Group B; n = 689) (counterpart/s of male infertility) from October 2021 to September 2022. Sub-clinical atherosclerosis was investigated before laparoscopy by ultrasound evaluation of carotid intima-media thickness (cIMT) and flow-mediated dilation (FMD). Serum samples were stored at -80 °C for evaluation of biochemical and inflammatory parameters. European Society of Cardiology guidelines were followed for standard definition/s. Participants/materials, setting, methods Traditional (obesity, hypertension) and metabolic (dyslipidaemia, diabetes, hyperhomocysteinemia) cardiovascular risk factor/s were assessed during evaluation and chemiluminescence respectively. Serum levels of interleukin (IL)-6, IL-8, IL-10, TNF-a, VEGF, and VCAM-1 were determined by enzyme-linked-immunosorbent assay/s. Univariate comparisons and bivariate correlations were conducted by Student’s t-test, and Spearman correlation respectively. Adjusted relative risks (aRR) with 95% confidence intervals (CI) were calculated by Cox-proportional hazard/s model among Group A vs Group B. Statistical significance was set at p &amp;lt; 0.05. Main results and the role of chance 62.95% and 37.04% women had stage III and stage IV endometriosis respectively as defined according to European Society for Human Reproduction and Embryology 2014 guideline. aRR (adjusted for demographic, obesity, diabetes mellitus, reproductive history, and migraine), documented a higher risk of hypertension (aRR 1.43; 95%CI 1.33–1.54) in women with endometriosis. On stratification of group A in less than and more than 40 years, laboratory parameters were similar except for significantly higher (p &amp;lt; 0.01) serum values of homocysteine, low density lipoprotein and cholesterol, in both age range of group A. FMD, indirect marker of endothelial dysfunction, was found to be lower in group A compared to controls (mean difference: −7.54, 95% CI: -10.32− -4.73; p&amp;lt; 0.001, however, cIMT was similar between both cohort/s. aRR of endometriosis in relation with hypercholesterolemia (1.07; 95%CI 1.01–1.25; p &amp;lt; 0.001), hypertension (1.22; 95%CI 1.14–1.30; p &amp;lt; 0.001), and hyperhomocysteinemia (1.04; 95%CI 0.96–1.12; p &amp;lt; 0.08) decreased with increasing age (&amp;gt;40 years). Systemic inflammation markers, showed an inverse relationship (p &amp;lt; 0.001) between values of FMD and serum levels of IL-6 (r = –0.34), TNF-a (r = –0.85), and VCAM-1 (r = –0.28) in group A. Other correlations were not statistically significant. Limitations, reasons for caution This observational study is not supported by patients with typical cardiovascular risk factors and hence limits generalizability of evidence to other ethnicities. Further, no information on hormonal treatments, such as dianogest (a synthetic progesterone) and/or leuprolide (gonadotropin-releasing hormone analog) are available to assess extent of association between endometriosis and CHD. Wider implications of the findings Higher propensity of subclinical atherosclerosis in younger women with laparoscopically-confirmed endometriosis represent higher systemic inflammation cueing to increased risk for CHD. This suggests the need for risk awareness and subsequent screening for CHD and healthy lifestyle promotion among gynaecologist/s and public health specialists. Trial registration number Not applicable

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

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

ASSESSMENT OF ENDOTHELIAL FUNCTION BY FLOW-MEDIATED DILATION IN WELL-CONTROLLED PATIENTS WITH RHEUMATOID ARTHRITIS

Objective: Endothelial dysfunction is considered as the primary pathophysiological process towards the development of cardiovascular disease (CVD). Patients with rheumatoid arthritis (RA) are at increased CVD risk attributed to the synergistic effect of chronic inflammation and traditional cardiovascular risk factors. However, it is uncertain whether endothelial function in RA is impaired even in the absence of cardiovascular comorbidities and pronounced inflammatory load. Design and method: Patients with RA who presented low levels of systemic inflammation and were free from cardiovascular comorbidities including hypertension, diabetes mellitus and established CVD, were studied. Non-RA individuals matched for age, sex and office systolic/diastolic blood pressure comprised the control group. Endothelial function was evaluated with the gold-standard flow-mediated dilation (FMD) in the brachial artery (Aloka ProSound A7 Ultrasound System). Results: A total of 22 female individuals were included in the study, of whom 10 were RA patients aged 57±13 years and 12 healthy volunteers aged 56±9 years. All patients with RA were at remission or low disease activity. Traditional CVD risk factors (age, systolic and diastolic blood pressure, smoking, body mass index and lipids) did not significantly differ between RA patients and controls. By contrast, significantly lower FMD values were observed in the RA group compared to controls [6.4 (5.0) vs 11.8 (5.2) %, p = 0.003]. The association between RA and FMD levels remained significant even after adjustment for age and systolic blood pressure (beta = 0.562, p = 0.009). Conclusions: Endothelial dysfunction is present in RA, even in a population characterized by the absence of hypertension and cardiovascular comorbidities and with relatively low systemic inflammatory burden. Further studies are warranted to verify the findings of this pilot study and delineate the role of endothelial dysfunction as a potential prognostic marker or therapeutic target.

Hyperinsulinemia Impaired Coronary Collateral Circulation in Patients with Chronic Total Coronary Occlusion.

Hyperinsulinemia impaired cardiovascular system and endothelial function in the population. The purpose of this study was to explore the relationship between hyperinsulinemia and coronary collateral circulation in patients with chronic total coronary occlusion. Patients with stable angina and at least one total coronary occlusion were enrolled in this study. Collateral grade was determined according to Rentrop's classification. Patients were divided into a good coronary collateral circulation (CCC) group (grade 2 or 3 collateral vessels, n = 223) and a poor CCC group (grade 0 or 1 collateral vessels, n = 115). Fasting insulin level (FINS) and fasting glucose level (FBS) were measured. Endothelial function evaluated by flow-mediated dilation (FMD). Serum FINS level was significantly increased in the poor CCC group (P < 0.01). Patients in the poor CCC group had higher levels of FBS, HbA1C, and homeostasis model assessment for insulin resistance (HOMA-IR) than patients in the good CCC group. The poor CCC group also had lower levels of FMD, lower LVEF and higher syntax scores than the good CCC group. Hyperinsulinemia (T3, FINS ≥15.22 μIU/mL) increased OR for the incidence of the poor CCC group (OR 2.419, 95% CI 1.780-3.287) in multivariate analysis. Multivariate logistic regression also revealed that diabetes, HbA1c, HOMA-IR, HDL-C and Syntax score were independent predictors of poor CCC (all P < 0.05). Hyperinsulinemia is a valuable predictor of poor collateral formation in patients with chronic total coronary occlusion.

Effect of Low Protein Diet Supplemented with Ketoanalogs on Endothelial Function and Protein-Bound Uremic Toxins in Patients with Chronic Kidney Disease.

Studies have demonstrated that a low-protein diet supplemented with ketoanalogs (KAs) could significantly retard progression of renal function in patients with chronic kidney disease (CKD) stages 3-5. However, its effects on endothelial function and serum levels of protein-bound uremic toxins remain elusive. Therefore, this study explored whether a low-protein diet (LPD) supplemented with KAs affects kidney function, endothelial function, and serum uremic toxin levels in a CKD-based cohort. In this retrospective cohort, we enrolled 22 stable CKD stage 3b-4 patients on LPD (0.6-0.8 g/day). Patients were categorized into control (LPD only) and study groups (LPD + KAs 6 tab/day). Serum biochemistry, total/free indoxyl sulfate (TIS/FIS), total/free p-cresyl sulfate (TPCS/FPCS), and flow-mediated dilation (FMD) were measured before and after 6 months of KA supplementation. Before the trial, there were no significant differences in kidney function, FMD, or uremic toxin levels between the control and study groups. When compared with the control group, the paired t-test showed a significant decrease in TIS and FIS (all p < 0.05) and a significant increase in FMD, eGFR, and bicarbonate (all p < 0.05). In multivariate regression analysis, an increase in FMD (p < 0.001) and a decrease in FPCS (p = 0.012) and TIS (p < 0.001) remained persistent findings when adjusted for age, systolic blood pressure (SBP), sodium, albumin, and diastolic blood pressure (DBP). LPD supplemented with KAs significantly preserves kidney function and provides additional benefits on endothelial function and protein-bound uremic toxins in patients with CKD.

Oxidative balance score reflects vascular endothelial function of Chinese community dwellers.

Background: The oxidative balance score (OBS) is a composite estimate of the overall pro- and antioxidant risk status in an individual. The aim of this study is to explore the association between the OBS and vascular endothelial function in Chinese community dwellers. Methods: In total, 339 community dwelling adults (aged 20-75years) were recruited in this study. The overall OBS was calculated on the basis of 16 pro- and antioxidant factors related to diet (measured by fasting blood samples) and lifestyle (evaluated by questionnaires). The dietary OBS and lifestyle OBS were calculated on the basis of the corresponding components. Serum iso-prostaglandin F2α (FIP) was measured to evaluate the oxidative stress degree, and brachial artery blood flow-mediated dilation (FMD) was measured for vascular endothelial function. The FIP and FMD levels were dichotomized as "low" or "high" using the corresponding median values (low FIP, n = 159; high FIP, n = 180; low FMD, n = 192; and high FMD, n = 147). The components of the OBS were compared between the stratified FIP and FMD groups. Logistic regression was used to analyze the OBS associations with FIP and FMD. Results: The higher overall OBS and dietary OBS were associated with lower FIP (p < 0.001), whereas the higher overall OBS (p < 0.01) and dietary OBS (p < 0.05) were associated with higher FMD. The lifestyle OBS was not associated with FIP and FMD (p > 0.05). Except for the body mass index (BMI) and low physical activity, all other OBS components were significantly different between the low FIP and high FIP groups (p < 0.05). Four diet-related antioxidants (α-carotene, zeaxanthin, α-tocopherol, and γ-tocopherol) showed significant differences between the high and low FMD groups (p < 0.05). Conclusion: The decreasing OBS level was associated with low endothelial function and high oxidative stress. The dietary OBS, rather than the lifestyle OBS, was more closely associated with endothelial function.

Endothelial function assessment by flow-mediated dilation of the brachial artery in acute kidney injury and chronic kidney disease.

Endothelial dysfunction has a significant role in the pathogenesis of cardiovascular events in patients with kidney dysfunction. The present study aimed to compare the level of endothelial dysfunction in patients with chronic kidney disease (CKD) and acute kidney injury (AKI) by brachial artery flow-mediated dilation (FMD) technique. Also, we sought to find whether this non-invasive technique may assist in accurately distinguishing the acute or chronic nature of kidney failure in patients presenting with uremia for the first time. Demographic and medical characteristics, and laboratory and renal ultrasonography data of the patients with AKI and CKD were collected and compared with a control group. Brachial artery FMD was measured using a Toshiba aplio 300 device with a 7.5 MHz linear probe. In a total of 175 patients with a mean (SD) age of 55.96(15.54) years, FMD% was significantly lower in the CKD and AKI patients compared to the control group (Mean±SD: 16.28%±10.52%), 16.28 %±4.35%, and 24.24±5.71, respectively, p<0.001). Among the different causes of AKI, contrast-induced nephropathy (10.78%±1.75%), volume depletion (14.87%±1.22%), and post-renal AKI (15.96%±1.54%) had the lowest levels of FMD. Also, a significant correlation between FMD and eGFR (r=0.26, P<0.001), serum Hb (r=0.18, P=0.013), Na (r=0.19, P=0.011), BUN (r=-0.21, P=0.005) and Cr (r=- 0.13, P=0.084) was reported. Compared to the control group, CKD and AKI patients showed greater levels of endothelial dysfunction as evidenced by lower brachial artery FMD. However, the FMD technique did not appear to be a practical method in differentiating CKD and AKI in patients presenting with uremia for the first time.

Clinical value of flow-mediated dilatation of brachial artery in hypertensive disorders complicating pregnancy.

Hypertensive disorders complicating pregnancy (HDCP) are common pregnancy-related disorders. In this study, we aimed to study the clinical value of flow-mediated dilation (FMD) in HDCP and its association with endothelial dysfunction and HDCP-related factors. 160 HDCP patients and 120 healthy pregnancies were enrolled in the study. The expressions of endothelial function markers and FMD were determined. In addition, their correlations in HDCP patients were also analyzed using Pearson's correlation analysis. FMD value decreased gradually from normal pregnancy to severe PE. The levels of plasma nitric oxidase (NO) were significantly lower in the HDCP group than those in the control group, while the levels of plasma endothelin-1 (ET-1) were increased dramatically in the HDCP group. Moreover, the levels of placental growth factor (PLGF) in HDCP women were significantly lower, while the soluble FMS-like tyrosine kinase 1 (sFLt-1) levels were markedly higher than those in control. In addition, the FMD value was correlated with the levels of plasma NO, ET-1, PLGF and sFlt1. It was also found that lower levels of FMD correspond to endothelial dysfunction and abnormal concentrations of PLGF and sFlt-1. The FMD value was associated with endothelial function indicators and could be a strong and non-invasive measure to predict HDCP. The association between the FMD values and endothelial function indicators in HDCP could be helpful for the prediction of pregnant hypertension more accurately.

Flow-Mediated Dilatation in the Assessment of Coronary Heart Disease: A Meta-Analysis.

Endothelial dysfunction may contribute to the increased morbidity and mortality associated with coronary heart disease (CHD). Flow-mediated dilatation (FMD) is the most popular noninvasive method for vascular endothelial function evaluation. This meta-analysis aimed to investigate the association between FMD and CHD. We searched the publications listed in the PubMed, Web of Science, Scopus, and Embase databases. Stata 14 software was used to analyze the data. Standardized mean difference (SMD) was used to calculate FMD levels, and the effect sizes were expressed with a 95% confidence interval (CI). I2 statistics were used to evaluate statistical heterogeneity. In this meta-analysis, 9 studies enrolled a total number of 943 participants, including 534 (56.63%) patients with CHD and 409 controls (43.37%). We found that patients with CHD showed a significantly lower FMD than the controls (SMD −0.706%; 95% CI: −0.985, −0.427; P=0.001) with high heterogeneity. In addition, funnel plot analysis suggested asymmetry that could be evidence of publication bias. But sensitivity analyses show that there were no influential studies. This meta-analysis provides evidence that patients with CHD show a significantly lower FMD than controls and highlights the literature on FMD as a hallmark in CHD diseases.