Significant Differences In Flow-mediated Dilation Research Articles

Limb-Specific Comparison of Flow-Mediated Dilation in Abdominal Obese Pre-menopausal Women

Abstract Purpose Normal aging can lead to arterial wall stiffening and development of atherosclerosis; however, the effects of overweight conditions can expedite the dysfunction of arterial health. In an earlier study, we identified in a group of abdominal obese pre-menopausal woman that during menses, these women had decreased vascular conductance of the brachial artery during dynamic hand-grip exercise. Endothelial function in abdominal obese (AO) premenopausal women could be associated with being highly sedentary which attenuates dilatory responses to FMD of both upper and lower limb vascular function. We hypothesized that the AO women would exhibit limb-specific differences in artery dilation with reduced dilation in the popliteal artery as compared to the brachial artery. Methods Artery dilatory responses in the brachial and popliteal arteries were assessed using flow-mediated dilation (FMD) in age-matched sedentary controls and AO groups during menses. Results Significant differences were found between groups including % BF, BMI, weight, waist to hip ratio, fasting blood glucose, and oxLDL. A between-group comparison revealed significantly lower percent dilation of the popliteal artery in AO participants compared to controls (p < 0.05) not present in the brachial arteries. Our results also indicate a difference in the time-to-peak (TP) of dilation between the control (33.38 ± 3.232) and AO (62.104 ± 5.813) groups (p < 0.01). Following FMD correction with shear rate as the covariate, significant differences in FMD between the brachial and popliteal artery were abolished. Conclusion We conclude that young, AO women show a limb-specific difference in dilation of the upper and lower extremities when compared to controls. Thus, reductions in FMD of the popliteal artery could be due to impaired dilation of the downstream resistance vasculature preventing increases in shear within the leg conduit arteries not as significantly in the arms.

Effects of Mediterranean Diet on Endothelial Reactivity in Individuals with High Cardiometabolic Risk: A Randomized Controlled Parallel-Group Preliminary Trial

Background: Endothelial dysfunction is recognized as an early modification involved in the pathogenesis of vascular diseases. Evidence suggests that the Mediterranean Diet (MD) is associated with endothelial function improvement and, in turn, plays an important role in atherosclerosis development and progression. Objectives: To evaluate both acute and sustained effects of the MD on endothelial function in patients with high cardiometabolic risk. Methods: A total of 25 subjects were randomly assigned to either the MD group or the Control Diet (CD) group according to a single-blind, parallel-group study design. Endothelial function was evaluated through non-invasive flow-mediated dilation (FMD) measurements at baseline (T0) and after 8 weeks (Tw8) of the MD or CD intervention, under both 12 h fast condition (fasting) and 2 h post-meal resembling the assigned diet (2 h). Assessments were conducted by a blinded sonographer. Results: FMD at T0-fasting was similar between MD and CD groups (6.11% ± 0.67 vs. 7.90% ± 1.65; p = 0.266). A significant difference in FMD between MD and CD groups was observed at T0-2h (12.14% ± 1.93 vs. 4.01% ± 1.03; p = 0.004), T8w-fasting (9.76% ± 1.18 vs. 5.03% ± 0.89; p = 0.008), and T8w-2h (8.99% ± 1.22 vs. 3.86% ± 0.52; p = 0.003). Oral glucose insulin sensitivity (OGIS) at T0 correlated with FMD percent changes from T0-fasting to T0-2h (r = 0.414, p = 0.044). After adjusting for age, gender, and OGIS, MD was an independent predictor of percent changes in FMD from T0-fasting to T0-2h (β: −0.582, p = 0.003), from T0-fasting to T8w-fasting (β: −0.498, p = 0.013), and from T0-fasting to T8w-2h (β: −0.479, p = 0.018). Conclusions: Adherence to the MD may improve endothelial function in both the short- and medium-term among patients at high cardiometabolic risk.

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.

DOES ENDOTHELIAL FUNCTION DIFFER AMONG SEXES IN PATIENTS WITH DIABETES OR KIDNEY DISEASE?

Objective: Endothelial dysfunction is a known driver of disease progression in both type 2 diabetes mellitus (T2DM) and kidney disease. Brachial artery flow-mediated dilation (FMD), representing endothelium-dependent nitric oxide-mediated dilation in response to increased shear stress, is considered gold standard to quantify macrovascular dysfunction non-invasively. As evidence is mounting that men are more likely to suffer from macrovascular dysfunction than women, we hypothesized that this would be reflected in patient populations with T2DM and/or kidney disease. Design and method: Preliminary baseline data was collected from 2 ongoing randomized controlled trials in patients with T2DM and in kidney transplant recipients (KTRs) 3 months post-transplantation. FMD was assessed with the semi-automated UNEX EF device under standardized conditions. Biochemical analyses were done using routine techniques. Images were manually analyzed by a single researcher (MR) using PCAnalysis software (version 1.0.14). Results: Twenty-five subjects, 13 with T2DM and 12 KTRs were included. As expected, patients with T2DM had a higher BMI, higher HbA1c but higher eGFR compared to KTRs (Table 1). Compared to KTRs, patients with T2DM presented with a significantly worse FMD (FMD= 4.50% [IQR=5.77]) vs 10.88% [6.48]). Overall, no significant difference in FMD between men and women was found (p=0.11), but higher values could be observed in females (FMD= 9.08% [IQR=6.97] vs 4.50% [7.88]). As depicted in Figure 2, this tendency was also observed in the 2 subgroups: KTRs (M: FMD = 9.07% [IQR=9.62] | F: 11.92% [5.16]) and T2DM (M: FMD = 3.90% [IQR=5.00%] | F: 7.09% [6.83]). Conclusions: Although no significant differences in vascular function between sexes were detected, our preliminary data showed a tendency for higher FMD-values in women; both in T2DM and KTRs. This supports the statement that male subjects seem to suffer more from macrovascular dysfunction. Further research is needed to elucidate the underlying pathways via which sex impacts the disease process in T2DM and kidney disease and to evaluate how personalized preventive lifestyle measures might differentially impact on outcome.

Non-invasive Estimation of Microvasculopathy & Endothelial Dysfunction in Stem Cell Transplant Recipients and its Relationship with GVHD.

Microvasculopathy and endothelial dysfunction play important roles in the development of post-transplant complications, including graft-versus-host disease (GVHD). We assessed structural microvasculopathy by employing nailfold video capillaroscopy (NFVC) and endothelial dysfunction via flow-mediated dilatation (FMD) of the brachial artery in recipients of hematopoietic stem cell transplantation. Recipients of stem cell transplantation were included in this study post day+100 and divided into two cohorts. The first cohort consisted of 35 recipients of allogeneic hematopoietic stem cell transplantation (HCT) and the second cohort was comprised of 31 recipients of autologous HCT. A third cohort included 35 healthy individuals. NFVC was conducted on the second to fifth fingers of both hands using an Optilia video capillaroscope at 200× magnification, and the images were analyzed according to the European Alliance of Associations for Rheumatology (EULAR) criteria. The following parameters were used to measure vasculopathy: (a) median capillary density, derived from the capillary density of eight fingers, (b) median capillary diameter, derived from maximum capillary apical diameters of eight fingers, and (c) significant neoangiogenesis (neoangiogenesis present in ≥2 fingers). FMD of the right brachial artery was observed by high-resolution ultrasonography using the principle of post-occlusive reactive hyperemia, and video images were analyzed using edge-detecting software. The median capillary diameter was significantly higher in the allo-HCT cohort (20.56±5.17 micrometer) compared to the auto-HCT cohort (16.19±3.31 micrometer; p<0.001) and healthy controls (14.66±2.61 micrometer; p<0.001). The median capillary density was significantly lower in the allo-HCT cohort (median: 6 capillaries/mm, range: 5-9 capillaries/mm) compared to the auto-HCT cohort (median: 8.5 capillaries, range: 5-12 capillaries/mm; p<0.001) and healthy controls (median: 8 capillaries/mm, range: 7-10.5 capillaries/mm; p<0.001). The allo-HCT cohort had a higher proportion of patients with significant neoangiogenesis (86%) than the auto-HCT cohort (10%) and healthy controls (9%). The presence of significant neoangiogenesis was more frequent in the subgroup of patients with a history of GVHD (93%) compared to the subgroup of patients without any history of GVHD (57%; p=0.044). No significant differences in NFVC parameters or FMD were observed between recipients of myeloablative and reduced-intensity conditioning regimens. There was no significant difference in NFVC parameters between the auto-HCT cohort and healthy controls. There was no significant difference in FMD among the three cohorts; however, a higher proportion of patients in the allo-HCT cohort (28%) had lower FMD than those in the auto-HCT cohort (3%) and healthy controls (6%), suggesting endothelial dysfunction. Our findings demonstrate the presence of structural microvasculopathy in allo-HCT recipients and suggest a possible role of alloreactivity in the pathogenesis of post-HCT microvasculopathy.

Assessment of High Frequency Imaging and Doppler System for the Measurements of the Radial Artery Flow-Mediated Dilation

Objectives: In the article we describe the new, high frequency, 20 MHz scanning/Doppler probe designed to measure the flow mediated dilation (FMD) and shear rate (SR) close to the radial artery wall. Methods: We compare two US scanning systems, standard vascular modality working below 12 MHz and high frequency 20 MHz system designed for FMD and SR measurements. Axial resolutions of both systems were compared by imaging of two closely spaced food plastic foils immersed in water and by measuring systolic/diastolic diameter changes in the radial artery. The sensitivities of Doppler modalities were also determined. The diagnostic potential of a high frequency system in measurements of FMD and SR was studied in vivo, in two groups of subjects, 12 healthy volunteers and 14 patients with stable coronary artery disease (CAD). Results: Over three times better axial resolution was demonstrated for a high frequency system. Also, the sensitivity of the external single transducer 20 MHz pulse Doppler proved to be over 20 dB better (in terms of a signal-to-noise ratio) than the pulse Doppler incorporated into the linear array. Statistically significant differences in FMD and FMD/SR values for healthy volunteers and CAD patients were confirmed, p-values < 0:05. The areas under Receiver Operating Characteristic (ROC) curves for FMD and FMD/SR for the prediction CAD had the values of 0.99 and 0.97, respectively. Conclusions: These results justify the usefulness of the designed high-frequency scanning system to determine the FMD and SR in the radial artery as predictors of coronary arterial disease.

PS-BPC02-2: CLINICAL IMPACTS OF ENDOTHELIUM-DEPENDENT FLOW-MEDIATED VASODILATION ASSESSMENT ON PRIMARY ALDOSTERONISM

Objective: Primary aldosteronism (PA) is defined as autonomous aldosterone production from the adrenal glands and represents the most common and treatable cause of hypertension. Also, it is well known that the incidence of cardiovascular morbidity is higher among patients with PA than among those with essential hypertension (EH). Histologically, PA is divided into two major subtypes, aldosterone-producing adenoma (APA) and bilateral idiopathic hyperplasia (IHA). 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 with PA. Design and Method: All patients were diagnosed with PA according to the guidelines of the Japan Endocrine Society. Flow-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 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. Results: No differences were found among the three groups (APA, IHA and EH) with regard to age, sex, duration of hypertension, body mass index, blood pressure, renal function and hemoglobin A1c. FMD 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 APA, IHA and EH groups (7.9 ± 1.3, 7.8 ± 1.0, 7.8 ± 1.1, respectively). Although no significant correlations were seen between FMD and background factors (i.e. age, body mass index, renal function, glucose and lipid metabolic parameters, and hormonal data) in the IHA group, FMD correlated negatively with BMI and plasma aldosterone concentration in the APA group (rs = -0.313, rs = -0.342, respectively). No significant difference in FMD (4.8 ± 1.4%, 4.5 ± 2.1%, respectively) or CAVI (8.1 ± 1.8, 8.0 ± 1.1, respectively) was seen between the KCNJ5-mutant group and the wild-type group. A cut-off FMD of 4.3% was selected for complete clinical success after adrenalectomy, offering 78% sensitivity and 80% specificity. Conclusions: Patients 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.

Endothelial dysfunction in the post-COVID-19 period: a meta-analysis

Abstract Background Coronavirus disease (COVID)-19 is an entity characterized by a cytokine storm and profound endotheliitis. Although several reports have pointed to the presence of endothelial dysfunction in the acute phase, data is accumulating regarding a possible prolonged adverse effect of COVID-19 on endothelial function. Purpose This systematic review and meta-analysis aims to evaluate the degree of endothelial impairment, assessed by flow-mediated dilation (FMD) of the brachial artery, in individuals recovering from COVID-19. Methods We conducted a systematic literature search for studies assessing FMD between in patients post-COVID-19 and controls. Exclusion criteria consisted of the absence of a control group, measurement of FMD only during the acute phase of the disease, and not reporting FMD in % change. Effect sizes were pooled via random-effect model and the results are expressed as uncorrected standardized mean difference (SMD), using the Cohen's d as the effect size metric, with 95% confidence intervals (CI). Between-study heterogeneity was assessed through the calculation of I2. Subgroup analysis according to follow-up duration and the presence of cardiovascular risk factor-matched controls was also carried out. Results Database search identified 51 studies. Following the application of the exclusion criteria, 7 studies were included in the meta-analysis (post-COVID-19: 342 subjects, Control: 273 subjects). Compared to controls, patients post-COVID-19 had significantly lower FMD% values (SMD: −1.06, 95% CI: −1.74 to −0.38, p&amp;lt;0.01, I2: 86%) (Figure 1). Results remained unaffected after exclusion of any single study using the leave-one-out method. Subgroup analysis revealed no significant differences in FMD between post-COVID-19 patients and controls according to follow-up duration or the presence of cardiovascular risk factor-matched control group. Conclusion Flow-mediated dilation of the brachial artery, indicative of endothelial dysfunction, was significantly reduced in post-COVID-19 subjects compared to non-infected controls. This finding may be an alarming sign towards a higher risk of incident cardiovascular events. Funding Acknowledgement Type of funding sources: None.

Differential effect of anthracycline and trastuzumab cancer therapeutic related vascular toxicity in patients with breast cancer

Abstract Introduction Both anthracyclines and trastuzumab are key regiments for the treatment of breast cancer, but their concurrent use is contraindicated because of their cardiotoxicity. Their effects on vascular function have been less well studied. Purpose We explored the effects of the anthracycline-based chemotherapy followed by trastuzumab-based treatment on endothelial function and arterial stiffness in patients with breast cancer. Methods 46 female patients (54.56±11.5 years old) with breast cancer scheduled for anthracycline-based chemotherapy followed by the combination of trastuzumab and taxane were enrolled. Trastuzumab was continued until the completion of one-year treatment. All participants underwent assessment of the brachial flow mediated dilatation (FMD), endothelial independent dilatation (EID), carotid-femoral pulse wave velocity (PWV) and augmentation index (AIx) at baseline (BL), at the end of anthracycline treatment (FU1), 3 months following initiation of trastuzumab with taxane (FU2) and at the completion of treatment with trastuzumab (FU3). Results Over the follow-up period (15 months) there was significant deterioration in FMD (p=0.04) (Table 1, Figure 1). Importantly, while there was no significant difference in FMD between BL vs FU1 (p=0.6), FMD has been significantly deteriorated over the treatment with trastuzumab with taxane FU1 vs FU2 (p=0.01) and FU2 vs FU3 (p=0.01) (Table 1, Figure 1). EID did not change over the follow-up period (Figure 1). Similarly, PWV has been significantly increased over the follow up period (p=0.03). There was no significant difference in PWV BL vs FU1 (p=0.1), however PWV has been significantly increased over the treatment with trastuzumab with taxane FU1 vs FU 2 (p=0.02) and FU2 vs FU3 (p=0.01) (Table 1, Figure 1). A similar pattern of impairment was observed with AIx (Table 1, Figure 1). Conclusion We report a significant adverse effect of the anthracycline- and trastuzumab-based therapy on the arterial stiffness and endothelial function. This effect is more considerable after the exposure to trastuzumab. Figure 1. Changes of FMD, PWV, Alx, EID during FU Funding Acknowledgement Type of funding source: None

A greater burden of atrial fibrillation is associated with worse endothelial dysfunction in hypertension.

Atrial fibrillation (AF) and hypertension often co-exist and both are associated with endothelial dysfunction. We hypothesised that AF would further worsen endothelium-dependent flow-mediated dilatation (FMD) in hypertension patients compared to those without AF. In a cross-sectional comparison, we measured brachial artery diameter at rest and during reactive hyperaemia following 5 min of arterial occlusion in two patient groups: AF (and hypertension) (n = 61) and hypertension control groups (n = 33). The AF (and hypertension) subgroups: permanent AF (n = 30) and paroxysmal AF (n = 31) were also assessed. The permanent AF patients received heart rate and blood pressure (BP) control optimisation and were then followed up after eight weeks for repeat FMD testing. There was no significant difference in FMD between AF (and hypertension) group and hypertension control group (4.6%, 95% CI [2.6-5.9%] vs 2.6%, 95% CI [1.9-5.3%]; p = 0.25). There was a significant difference in FMD between permanent AF and paroxysmal AF groups (3.1%, 95% CI [2.3-4.8%] vs 5.9%, 95% CI [4.0-8.1%]; p = 0.02). Endothelium-dependent FMD response showed a non-significant improvement trend following eight weeks of heart rate and BP optimisation (3.1%, 95% CI [2.3-4.8%] (baseline) vs 5.2%, 95% CI [3.9-6.5%] (follow up), p = 0.09). Presence of AF generally does not incrementally worsen endothelial dysfunction in hypertension patients, although the duration and frequency of AF (paroxysmal AF to permanent AF) does lead to worsening endothelial function. Eight weeks of BP optimisation did not significantly improve endothelial dysfunction as measured by FMD.

405Acute and short-term effects of diesel exhaust fumes exposure on arterial wall properties, inflammatory process and fibrosis-fibrinolysis status

Abstract Introduction Exhaust fumes from diesel engines are a complex mixture of toxic compounds with a wide variety of harmful effects. The acute effects of diesel exhaust fumes on the cardiovascular system are well-known. However, their short-term impact has not been thoroughly studied. Purpose To study the acute and short-term (24 h) effects of diesel exhaust particles (DEPs) on endothelial function, arterial wall properties, inflammatory process and fibrosis-fibrinolysis status. Methods In this blind cross over study, 40 healthy volunteers (median age 40 years old) have been exposed to diesel exhaust particles (DEPs) and then to filtered air (FA) over a 2-hour session with a wash out period of 4 weeks. Exposure to DEPs was calibrated based on the mass of microparticles less than 2,5 microns in diameter (PM 2,5). Flow-mediated-dilation (FMD) was used to estimate endothelial function. Pulse wave velocity (PWV) and augmentation index (AIx) assessed central aortic stiffness and arterial reflected waves respectively. C reactive protein (CRP) was measured to determine the inflammatory status, as well as fibrinogen and protein C levels to evaluate the impact on the coagulation cascade. All measurements were performed before each session (T0), at the end of the 2 hours exposure session (T2) and 24 hours after completion of each session (T24). Variables with normal distribution are presented as mean±SD otherwise as median±SEM. Results At T0 of DEP and FA exposure there was no significant difference in FMD, PWV, AIX, CRP, protein C and fibrinogen levels. Exposure to DEP decreased significantly FMD (T0: 11.97±4.61% vs T2: 7.71±3.36% vs. T24: 6.17±3.19%, p&lt;0.001) and increased PWV (T0: 6.09±1.03m/sec vs T2: 7.22±1.31m/sec vs. T24: 6.90±1.03m/sec, p&lt;0.001), AIx (T0: 8.17±3.19% vs T2: 12.71±3.36% vs. T24: 13.17±4.61%, p&lt;0.001), CRP (T0: 1.41±0.18 mg/L vs T2: 1.99±0.21mg/L vs. T24: 2.08±0.24mg/L, p=0.04) and fibrinogen levels (T0: 269±44 mg/dL vs T2: 331±75 mg/dL vs. T24: 307±51 mg/dL, p=0.002). Protein C was significantly reduced (T0: 121±26% vs T2: 104±21% vs. T24: 105±20%, p=0.003). Exposure to FA had no significant impact on the study parameters. Graph of results Conclusion Exposure to diesel exhaust fumes may have significant adverse effects on the cardiovascular system with impairment of endothelial function, arterial wall properties, inflammatory status and fibrosis-fibrinolysis parameters not only during the exposure period but as far as 24 hours after exposure. Acknowledgement/Funding None

Assessment of subclinical atherosclerosis in psoriatic arthritis patients without clinically overt cardiovascular disease or traditional atherosclerosis risk factors.

Cardiovascular disease (CVD) is more prevalent in almost all patients with chronic inflammatory musculoskeletal diseases than in their healthy counterparts. The aim of this study was to assess the presence of subclinical atherosclerosis in patients with psoriatic arthritis (PsA) in comparison with patients with rheumatoid arthritis (RA) and healthy controls. A total of 30 patients with PsA, 30 patients with RA, and 30 healthy controls were enrolled in this parallel group study. Demographic, clinical, and laboratory data of the groups were recorded. The Disease Activity Score-28 tool was used for joint assessment. The erythrocyte sedimentation rate and C-reactive protein level were measured as acute phase reactants. Flow-mediated dilatation (FMD) and carotid intima media thickness (CIMT) were also measured in all participants. The median duration of disease in patients with PsA was 60 months (range: 8-216 months). A total of 22 of 30 (73.3%) PsA patients had a diagnosis of psoriasis and 13 (48.1%) had active disease. The study groups were similar with regard to age, gender, and body mass index data. In all, 23 (76.7%) of the PsA patients and 5 (16.7%) of the RA patients were using an anti-tumor necrosis factor alpha therapy (p<0.001). The FMD percentage was significantly smaller in both the PsA and the RA patients than in the healthy controls (p<0.001). The median CIMT was greater in the RA patients compared with the PsA patients and the healthy controls (p=0.008). There was no significant difference in FMD or CIMT between patients with and without an active joint lesion. Endothelial functions were impaired in PsA, as in RA, in the absence of conventional risk factors or overt CVD. This finding may show a potential association between PsA, atherosclerosis, and CVD.

The effects of vildagliptin compared with metformin on vascular endothelial function and metabolic parameters: a randomized, controlled trial (Sapporo Athero-Incretin Study 3)

BackgroundDipeptidyl peptidase-4 (DPP-4) inhibitors may have protective effects in the early stage of atherosclerosis in patients with type 2 diabetes, although similar effects in advanced atherosclerosis were not shown in recent randomized placebo-controlled studies. Therefore, we investigated the efficacy of DPP-4 inhibitor on endothelial function and glycemic metabolism compared with high-dose metformin.MethodsIn this multicenter, open-labeled, prospective, randomized, parallel-group comparison study, patients with type 2 diabetes treated with low-dose metformin (500–750 mg/day) were enrolled and randomly assigned to a vildagliptin, a DPP-4 inhibitor, add-on group (Vilda) or a double dose of metformin group (high Met) for 12 weeks. Flow-mediated dilation (FMD) and serum metabolic markers were assessed before and after treatment. In addition, glycemic control and metabolic parameters were also assessed.ResultsNinety-seven subjects (aged 58.7 ± 11.0 years; body mass index, 25.9 ± 4.4 kg/m2; HbA1c, 7.3 ± 0.5%; FMD, 5.8 ± 2.6%) were enrolled. Eight subjects dropped out by the end of the study. There were no significant differences between the two groups in baseline characteristics. After 12 weeks, HbA1c was significantly improved in the Vilda group compared with the high Met group (− 0.80 ± 0.38% vs. − 0.40 ± 0.47%, respectively; p < 0.01). However, there were no significant differences in FMD (− 0.51 [− 1.08–0.06]% vs. − 0.58 [− 1.20–0.04]%). Although the apolipoprotein B/apolipoprotein A1 ratio was significantly reduced in the Vilda group compared with baseline (0.66–0.62; p < 0.01), the change did not differ significantly between the two groups (− 0.04 vs. 0.00; p = 0.27). Adiponectin levels were significantly increased in the Vilda group compared with the high Met group (0.75 μg/mL vs. 0.01 μg/mL; p < 0.01).ConclusionsRegardless of glycemic improvement, combination therapy of vildagliptin and metformin did not affect endothelial function but may exert favorable effects on adipokine levels and lipid profile in patients with type 2 diabetes without advanced atherosclerosis.

MATERNAL CARDIOVASCULAR EFFECTS OF PLACENTAL DYSFUNCTION IN THE 2ND TRIMESTER

Preeclampsia occurs in 3% of pregnancies. Women who develop severe/early-onset PE (sPE) demonstrate extensive cardiovascular abnormalities. The purpose of this study was to compare baseline measures of cardiovascular function in pregnant women at high-risk of developing sPE to those observed in healthy pregnant controls in the 2nd trimester. Pregnant women at high-risk of sPE (n=24) and healthy pregnant controls (n=20) are recruited to undergo baseline assessment at 22-26 weeks of gestation. Cardiovascular function is assessed by heart rate (HR), blood pressure (BP), non-invasive cardiac output (CO) measurement (NICOM), flow-mediated dilation (FMD), and uterine artery Doppler. Urine and bood samples are also collected. 23 high-risk women and 13 controls have participated in the study to date. There were no significant differences in maternal age (32±4 vs 34±3; p=0.12), maternal BMI (28.4±4 kg/m2 vs 25.7±5 kg/m2; p=0.06) or gestational age at the time of the study (24±2 weeks vs 24±1 weeks; p=0.44) between the high-risk group and controls. Gestational age at delivery was significantly earlier in the high-risk group when compared to controls (34±3 weeks vs 39±2 weeks; p<0.001), with 57% of the high-risk women developing sPE vs 0% of the healthy controls to date. At baseline, HR was higher in the high-risk group as compared to controls (84±12 bpm vs 75±6 bpm; p=0.03). Systolic and diastolic BP were also higher in the high-risk group (118±11 mmHg vs 108±11 mmHg; p=0.03, 69±10 mmHg vs 62±4 mmHg; p=0.04). Systolic blood pressure correlated positively with serum uric acid levels (p=0.02). Despite their higher HR, CO was significantly lower in the high-risk group as compared to controls (5.9±0.9 L/min vs 7.6±1 L/min; p<0.001). Systemic vascular resistance was also higher in the high-risk group (1189±248 dyn·s·cmˆ5 vs 872±135 dyn·s·cmˆ5; p<0.001). There was no significant difference in FMD between high-risk and control groups (6.4±4% vs 8.8±5%; p=0.19). Uterine artery Doppler-based pulsatility index was significantly higher in the high-risk group at baseline (1.8±0.5 vs 0.88±0.1; p<0.001), and correlated positively with systemic vascular resistance (p<0.001). Women at high-risk of developing sPE exhibit abnormalities in baseline cardiovascular function.

Differences in angiotensin (1–7) between men and women

In experimental animal models of hypertension, angiotensin (1-7) [ANG-(1-7)] is higher in females compared with males; however, it is less clear whether the same applies to humans. Therefore, this study sought to compare circulating concentrations of ANG-(1-7) in apparently healthy men and women under normal physiological conditions. With the use of a cross-sectional experimental design, blood was collected in EDTA anticoagulant from 42 volunteers (21 men and 21 women; and age range, 19-48 yr) for analysis of plasma concentrations of ANG-(1-7) and ANG II. Blood pressure was measured and vascular endothelial function was determined (n = 25) using the brachial artery flow-mediated dilation (FMD) test. As a result, women exhibited a higher circulating concentration of ANG-(1-7) (P = 0.04) compared with men, whereas values of ANG II were similar between groups. Baseline arterial diameter, peak diameter, and shear rate were significantly greater (P < 0.02) in men compared with women. No significant differences in FMD, FMD normalized for shear, or time to peak dilation were observed between men and women. In addition, a positive correlation between ANG-(1-7) and FMD (P = 0.04) and negative association between ANG-(1-7) with ANG II (P = 0.01) were only identified in men, whereas a positive relationship between ANG-(1-7) and diastolic blood pressure (P = 0.03) was observed in women. , women exhibit significantly higher plasma concentrations of ANG-(1-7) compared with men. In addition, this study describes a relationship between ANG-(1-7), vascular function, and diastolic blood pressure that appears to be sex dependent.

Endothelial Function and Vascular Properties in Children with Sickle Cell Disease.

Sickle cell disease (SCD) is an inherited disorder characterized by recurrent painful crises with ischemia resulting from vascular occlusion. Adults with SCD have increased arterial stiffness and reduced flow-mediated dilation (FMD), due to impaired release of substances such as nitric oxide. We aimed to assess the vascular properties of carotid and brachial arteries in children with SCD compared with a control group without cardiovascular risk factors. Thirty patients with SCD, mean age 12.3±4.5years, were prospectively enrolled. A control group was made up of 30 age- and gender-matched healthy subjects. Carotid intima-media thickness (IMT), cross-sectional compliance (CSC), cross-sectional distensibility (CSD), diastolic wall stress (DWS), incremental elastic modulus (Einc), and FMD were determined in both groups. There was no significant difference in FMD between the two groups (8.2±5.0% in the SCD group vs. 9.3±4.2% in the control group, P=0.15). There was no significant correlation between FMD and age, hemoglobin, LDH level, or transcranial Doppler findings. CSD was significantly elevated in the SCD group (0.96±0.44 vs. 0.59±0.21, P=0.0002), whereas DWS and Einc were significantly lower in the SCD group. CSC did not differ significantly between the two groups. Children with SCD have no marked endothelial dysfunction or change in arterial stiffness. These manifestations may be related to disease severity and duration. Changes may become evident later in life as the disease progresses.

Noninvasive assessment of endothelial function and vascular parameters in patients with familial and nonfamilial hypercholesterolemia

Endothelial dysfunction is one of the markers of atherosclerosis. The aim of the study was to evaluate endothelial function by assessing flow-mediated dilation (FMD) and to measure the parameters of brachial arterial stiffness in patients with familial hypercholesterolemia (FH) and those with high low-density lipoprotein (LDL) cholesterol levels without FH mutations (nonfamilial hypercholesterolemia - non-FH). The study involved 60 patients (mean age, 41.9 ±7.7 y) without documented cardiovascular events and clinical symptoms of cardiovascular diseases: 21 patients with elevated plasma LDL cholesterol levels and genetically confirmed FH, 19 patients with elevated LDL cholesterol levels and without FH mutations, and 20 healthy controls. In each patient, ultrasound imaging was used to assess endothelium-dependent FMD and nitroglycerin-induced endothelium-independent dilation (EID) in the brachial artery. In addition, echo-tracking and photoplethysmography were used to assess the parameters of arterial stiffness. FMD was significantly lower in patients with FH (11.0% ±9.9% vs. 21.0% ±14.3%, P <0.01) and non-FH (14.2% ±10.1% vs. 21.0% ±14.3%, P <0.05) compared with controls. EID and arterial stiffness parameters were similar between the groups. Reduced FMD may suggest endothelial dysfunction. A lack of significant differences in arterial stiffness parameters may indicate that vascular remodeling is not advanced in patients with elevated LDL cholesterol levels. A lack of significant differences in FMD and arterial stiffness between patients with and without FH may indicate that FH mutation itself is not the main determinant of endothelial dysfunction and vascular remodeling in younger patients with hypercholesterolemia.

Leptin is associated with vascular endothelial function in overweight patients with type 2 diabetes.

BackgroundThe adipocyte-derived hormone leptin plays a key role in the regulation of appetite and body weight. Recent studies have suggested that leptin is also involved in the pathogenesis of obesity-related atherosclerosis and cardiovascular disease. In this study, we investigated the association of plasma leptin levels with vascular endothelial function in lean and overweight patients with type 2 diabetes.MethodsOne hundred seventy-one type 2 diabetic patients, of which 85 were overweight (body mass index (BMI) ≥ 25 kg/m2), were enrolled in this cross-sectional study. Plasma leptin concentrations were measured by enzyme-linked immunosorbent assay. Flow-mediated dilatation (FMD) of the brachial artery was measured to evaluate vascular endothelial function using ultrasound.ResultsNo significant difference in FMD was found between the lean and overweight groups (7.0 ± 3.8% and 6.5 ± 3.6%, respectively; p = 0.354). FMD was negatively correlated with age (r = −0.371, p < 0.001) and serum creatinine levels (r = −0.236, p = 0.030), but positively correlated with BMI (r = 0.330, p = 0.002) and plasma leptin levels (r = 0.290, p = 0.007) in the overweight group. FMD was not associated with any parameters in the lean group. Multiple regression analysis including possible atherosclerotic risk factors revealed that the plasma leptin level (β = 0.427, p = 0.013) was independently associated with FMD in the overweight group (R2 = 0.310, p = 0.025), but not the lean group.ConclusionPlasma leptin levels are associated with vascular endothelial function in overweight patients with type 2 diabetes.

Correlation between brachial artery flow-mediated dilation and endothelial microparticle levels for identifying endothelial dysfunction in children with Kawasaki disease

We investigated vascular endothelial dysfunction by sonographic features of flow-mediated dilation (FMD) and circulating endothelial microparticles (EMPs) in Kawasaki disease (KD). Twenty-eight patients with KD were prospectively grouped according to stage of disease: acute, subacute, and convalescent. In addition, 28 healthy children and 28 febrile children were selected as controls. And cases in the convalescent phase were divided into two subgroups: coronary artery lesion (CAL) and no coronary lesion (NCAL). CD144(+)/CD42b(-), CD62E(+), and CD105(+) EMPs were measured by flow cytometry; FMD was obtained by sonography. There were significant differences in FMD among the five groups. When compared with healthy controls, there were significantly greater numbers of CD144(+)/CD42b(-), CD62E(+), and CD105(+) EMPs and a higher proportion of CD62E(+) EMPs in KD patients. The proportions and numbers of CD144(+)/CD42b(-), CD62E(+), and CD105(+) EMPs in KD patients were not statistically different than in febrile controls. There were no significant differences in FMD and EMPs between the CAL and NCAL subgroups. There were significantly negative correlations between the values of FMD and EMPs in the three phases of KD. The increased levels of EMPs have significant correlation with decreased values of FMD, both of which may reflect endothelial dysfunction in child KD.

Subclinical Atherosclerosis, Endothelial Function, and Serum Inflammatory Markers in Chronic Kidney Disease Stages 3 to 4

Different inflammatory markers, brachial artery flow-mediated dilatation (FMD), and brachial intima-media thickness (bIMT) were measured in 50 patients with chronic kidney disease (CKD) stages 3 to 4 with estimated glomerular filtration rate (eGFR) and 35 age- and gender-matched controls. The bIMT was significantly increased in the patients with CKD compared with controls (0.43 mm [0.42, 0.45] vs 0.34 mm [0.32, 0.36]; P < .001). There was no significant difference in FMD between the study groups (4.7% vs 5.3%; P = .56). There were significant correlations between bIMT and high-sensitive C-reactive protein, vascular cellular adhesion molecule 1, tumor necrosis factor, and interleukin 6 (P < .05). However, eGFR adjusted for age and gender was the best predictor of bIMT. In conclusion, bIMT and inflammatory markers were increased in patients with CKD compared with the controls. Furthermore, significant correlations between bIMT and inflammatory activity in patients with CKD were observed. The eGFR adjusted for age and gender was the best predictor of bIMT.