Change In Flow-mediated Dilation Research Articles

DPP-4 inhibitor and alpha-glucosidase inhibitor equally improve endothelial function in patients with type 2 diabetes: EDGE study.

BackgroundAlpha glucosidase inhibitor (GI) attenuates postprandial hyperglycemia (PPH) and reduces the risk of cardiovascular events in patients with impaired glucose tolerance or type 2 diabetes. Dipeptidyl peptidase 4 (DPP-4) inhibitors also attenuate PPH. PPH is one of the factors leading to endothelial dysfunction which is an early event in the pathogenesis of atherosclerosis. Furthermore, DPP-4 inhibitors protect endothelial function through a GLP-1-dependent mechanism. However, the impact of these two types of drugs on endothelial dysfunction in patients with type 2 diabetes has not been fully elucidated. We compared the effects of sitagliptin, a DPP-4 inhibitor, and voglibose, an alpha GI, on endothelial function in patients with diabetes.MethodsWe conducted a randomized prospective multicenter study in 66 patients with type 2 diabetes who did not achieve the treatment goal with sulfonylurea, metformin or pioglitazone treatment; 31 patients received sitagliptin treatment and 35 patients, voglibose treatment. The flow-mediated dilatation (FMD) of the brachial artery was measured in the fasting state at baseline and after 12 weeks of treatment. The primary endpoint was a change in FMD (ΔFMD) from the baseline to the end of follow-up. The effects of sitagliptin and voglibose on FMD were assessed by ANCOVA after adjustment for the baseline FMD, age, sex, current smoking, diabetes duration and body mass index. Secondary efficacy measures included changes in HbA1c, GIP, GLP-1, C-peptide, CD34, lipid profile, oxidative stress markers, inflammatory markers and eGFR and any adverse events.ResultsΔFMD was significantly improved after 12 weeks of treatment in both groups, and there was no significant difference in ΔFMD between the two groups. There were no significant differences in changes in HbA1c, GIP, GLP-1, C-peptide, lipid profile, oxidative stress marker, inflammatory marker and eGFR between the two groups. Compared with voglibose, sitagliptin significantly increased the circulating CD34, a marker of endothelial progenitor cells. Adverse events were observed in 5 patients in only the voglibose group (diarrhea 1, nausea 1, edema 2 and abdominal fullness 1).ConclusionsSitagliptin improved endothelial dysfunction just as well as voglibose in patients with type 2 diabetes. Sitagliptin had protective effects on endothelial function without adverse events.Trial registrationregistered at http://www.umin.ac.jp/ctrj/ under UMIN000003951

High-fat meals do not impair postprandial endothelial function in HIV-infected and uninfected men.

Prior studies have demonstrated impaired endothelium-dependent flow-mediated dilation (FMD) in healthy subjects following a high-fat meal. Compared to uninfected individuals, HIV-infected persons have been shown to have impaired FMD. We examined the effect of two different high-fat meals on endothelial function in HIV-infected and uninfected men. We performed a randomized, parallel group crossover study comparing 47 white men [18 HIV-uninfected, 9 HIV-infected and antiretroviral therapy (ART)-naïve, and 20 HIV-infected men on ART]. Fasting participants consumed one of two randomly assigned high-fat meals of either saturated or polyunsaturated fat, followed at least 24 h later by the other meal. Brachial artery ultrasound measurements to assess vascular reactivity were performed before and 3 h after each dietary challenge. There was no significant difference in mean baseline or postprandial FMD between HIV-infected and HIV-uninfected participants (mean baseline FMD±SD, 9.0%±5 vs. 9.2%±5, p=0.9; mean postprandial FMD±SD, 9.0%±4.7 vs. 9.1%±4.7, p=0.96, respectively). No significant difference in baseline or postprandial change in FMD was found between meals or HIV treatment groups. Fasting lipids and glucose, CD4(+) count, and viral load did not predict FMD in HIV-infected participants. In contrast to previous reports, this study did not demonstrate impaired endothelium-dependent vasodilation after high-fat meals in either HIV-infected or HIV-uninfected men. Moreover, HIV infection itself may not be the primary explanation for the abnormal endothelial function reported in HIV-infected individuals.

Changes of plasma concentration of osteoprotegerin and its association with endothelial dysfunction before and after hypouricemic therapy in patients with hyperuricemia

Objective. Osteoprotegerin (OPG) is a secreted glycoprotein in the regulation of bone turnover. Recently, many studies showed that OPG acts as an important regulatory molecule in the vascular systems. Our objective was to examine the plasma OPG levels alteration and its association with endothelial function before and after hypouricemic therapy in patients with hyperuricemia.Methods. Thirty patients (28 males and 2 females, serum uric acid > 7.0 mg/dl) with hyperuricemia were selected. Thirty healthy individuals (28 males and 2 females) with normal serum uric acid were also selected as control. Patients were administered with hypouricemic therapy for 6 months. Plasma OPG concentration was measured in duplicate using a sandwich ELISA and high-resolution ultrasound was used to measure brachial artery diameter at rest, after reactive hyperemia and after sublingual glyceryltrinitrate.Results. Plasma OPG levels in patients with hyperuricemia before hypouricemic therapy was significantly higher than those in controls (3.39 ± 0.25 vs. 2.05 ± 0.74 ng/L, p < 0.01). After hypouricemic therapy, OPG levels decreased markedly (2.54 ± 0.38 ng/L, p < 0.01). Flow-mediated dilation (FMD) in patients with hyperuricemia was 3.07 ± 1. 23%, which was significantly lower than that in control subjects (4.62 ± 0.69%, p < 0.01), and it improved significantly after hypouricemic therapy (3.91 ± 1.37%, p < 0.01). The absolute changes in OPG showed a significant positive correlation with the changes in serum uric acid (p < 0.05) and negative correlation with the changes in FMD (p < 0.01) in patients with hyperuricemia during the course of hypouricemic therapy.Conclusion. The current study demonstrates that plasma OPG levels increased significantly in patients with hyperuricemia and decreased significantly after hypouricemic therapy, and are correlated with FMD. These findings support the growing concept that elevated plasma OPG levels may be involved with the development of endothelial dysfunction in patients with hyperuricemia.

Efficacy and safety of functional electrical stimulation of lower limb muscles in elderly patients with chronic heart failure: A pilot study

Exercise training is an established modality in chronic heart failure. Functional electrical stimulation (FES) is an effective alternative mode of training in patients unwilling or unable to exercise; however, it has not been investigated in elderly patients. We sought to investigate the effects of FES on functional status, quality of life, emotional status and endothelial function in chronic heart failure patients aged 70 years or higher. Thirty patients with stable systolic chronic heart failure (mean age 75 ± 3 years, New York Heart Association (NYHA) class II/III, 37%/63%) randomly underwent a six-week FES training programme or placebo. Questionnaires addressing quality of life (Kansas City Cardiomyopathy Questionnaire (KCCQ), functional and overall) and emotional stress (Zung self-rating depression scale (SDS), Beck Depression Inventory (BDI)), as well as endothelial function (flow-mediated dilatation) were assessed at baseline and upon protocol completion. A significant improvement in NYHA class (p=0.005), KCCQ-functional (F=68.6, p for interaction<0.001), KCCQ-overall (F=66.9, p<0.001), BDI (F=66.3, p<0.001) and Zung SDS (F=95.1, p<0.001) was observed in the FES group compared to placebo. Patients in the FES group also had a significant increase in flow-mediated dilatation compared with placebo (F=59.1, p<0.01). FES-induced per cent change in flow-mediated dilatation was significantly correlated with respective per cent change in KCCQ functional (r=0.386, p=0.039). In this pilot study, FES effectively improved functional status, quality of life, motional stress and endothelial function in elderly chronic heart failure patients and warrants further investigation in this particular group of patients.

SAT0162 Assessment of Subclinical Atherosclerosis (Flow Mediated Dilatation and Arterial Stiffness) after 24 Weeks of Tocilizumab Therapy in 22 Patients with Rheumatoid Arthritis

BackgroundSubclinical atherosclerosis and an increased incidence of cardiovascular diseases have been observed in rheumatoid arthritis (RA). Inflammation and traditional risk factors could be involved in the pathogenesis. Tocilizumab, an inhibitor...

Effects of hypercapnia on peripheral vascular reactivity in elderly patients with acute exacerbation of chronic obstructive pulmonary disease.

Blood acid-base imbalance has important effects on vascular reactivity, which can be related to nitric oxide (NO) concentration and increased during hypercapnia. Release of NO seems to be linked to H+ and CO2 concentration and to exacerbation of chronic obstructive pulmonary disease (COPD), a common medical condition in the elderly. Flow-mediated dilation (FMD), a valuable cardiovascular risk indicator, allows assessment of endothelial-dependent vasodilation, which is to a certain extent mediated by NO. We investigated the effects of hypercapnia and acid-base imbalance on endothelial-dependent vasodilation by measurement of FMD in 96 elderly patients with acute exacerbation of COPD. Patients underwent complete arterial blood gas analysis and FMD measurement before (phase 1) and after (phase 2) standard therapy for acute exacerbation of COPD and recovery. Significant differences between phase 1 and phase 2 were observed in the mean values of pH (7.38±0.03 versus 7.40±0.02, P<0.001), pO2 (59.6±4.9 mmHg versus 59.7±3.6 mmHg, P<0.001), pCO2 (59.3±8.63 mmHg versus 46.7±5.82 mmHg, P<0.001), FMD (10.0%±2.8% versus 8.28%±2.01%, P<0.001) and blood flow rate (1.5±0.3 m/s versus 1.5±0.3 m/s, P=0.001). FMD values were positively correlated with pCO2 values (r=0.294, P=0.004) at baseline. A significant correlation was also found between relative changes in FMD and pCO2 levels, passing from phase 1 to phase 2 (r=0.23, P=0.023). Patients with higher baseline endothelium-dependent vasodilation as evaluated by FMD showed greater modification with regard to pCO2 changes (2.6±1.39 versus 1.59±1.4, P=0.012). In conclusion, endothelium-dependent vasodilation as evaluated by FMD was elevated during hypercapnia, and varied significantly according to pCO2 changes in patients with higher baseline levels, suggesting that vascular reactivity in acute COPD exacerbations in the elderly depends on integrity of the vascular endothelium.

Lowering of oxidative stress improves endothelial function in healthy subjects with habitually low intake of fruit and vegetables: A randomized controlled trial of antioxidant- and polyphenol-rich blackcurrant juice

Inadequate intake of the recommended five-a-day fruit and vegetable portions might contribute to increased cardiovascular disease risk. We assessed the effects of dietary intake of a blackcurrant juice drink, rich in vitamin C and polyphenols, on oxidative stress and vascular function. This was a double-blind, placebo-controlled, parallel group study of 66 healthy adults who habitually consume <2 portions of fruit and vegetables per day. Participants were randomly allocated to consume 250ml of placebo (flavored water) or low or high blackcurrant juice drink four times a day for 6 weeks. Flow-mediated dilation (FMD) and plasma concentrations of F2-isoprostanes and vitamin C were measured. In the high blackcurrant juice drink group FMD increased significantly (5.8±3.1 to 6.9±3.1%, P=0.022) compared with the placebo group (6.0±2.2 to 5.1±2.4%). Plasma vitamin C concentration increased significantly in the low (38.6±17.6 to 49.4±21.0µmol/L, P<0.001) and high (34.6±20.4 to 73.8±23.3µmol/L, P<0.001) blackcurrant juice drink groups compared with the placebo group (38.1±21.0 to 29.0±17.6µmol/L). F2-isoprostane concentrations were significantly lower in the high blackcurrant juice drink group (225±64pg/ml) compared with the low blackcurrant juice drink (257±69pg/ml, P=0.002) and placebo group (254±59pg/ml, P=0.003). At follow-up, changes in plasma vitamin C correlated significantly with changes in FMD (r=0.308, P=0.044). Consumption of blackcurrant juice drink high in vitamin C and polyphenols can decrease oxidative stress and improve vascular health in individuals with habitually low dietary fruit and vegetable intake.

Bezafibrate improves postprandial hypertriglyceridemia and associated endothelial dysfunction in patients with metabolic syndrome: a randomized crossover study

BackgroundPostprandial elevation of triglyceride-rich lipoproteins impairs endothelial function, which can initiate atherosclerosis. We investigated the effects of bezafibrate on postprandial endothelial dysfunction and lipid profiles in patients with metabolic syndrome.MethodsTen patients with metabolic syndrome were treated with 400 mg/day bezafibrate or untreated for 4 weeks in a randomized crossover study. Brachial artery flow-mediated dilation (FMD) and lipid profiles were assessed during fasting and after consumption of a standardized snack. Serum triglyceride and cholesterol contents of lipoprotein fractions were analyzed by high-performance liquid chromatography.ResultsPostprandial FMD decreased significantly and reached its lowest value 4 h after the cookie test in both the bezafibrate and control groups, but the relative change in FMD from baseline to minimum in the bezafibrate group was significantly smaller than that in the control group (-29.0 ± 5.9 vs. -42.9 ± 6.2 %, p = 0.04). Bezafibrate significantly suppressed postprandial elevation of triglyceride (incremental area under the curve (AUC): 544 ± 65 vs. 1158 ± 283 mg h/dl, p = 0.02) and remnant lipoprotein cholesterol (incremental AUC: 27.9 ± 3.5 vs. 72.3 ± 14.1 mg h/dl, p < 0.01). High-performance liquid chromatography analysis revealed that postprandial triglyceride content of the chylomicron and very low-density lipoprotein fractions was significantly lower in the bezafibrate group than in the control group (p < 0.05).ConclusionBezafibrate significantly decreased postprandial endothelial dysfunction, and elevations of both exogenous and endogenous triglycerides in patients with metabolic syndrome, suggesting that bezafibrate may have vascular protective effects in these patients.Clinical trial registrationUnique Identifiers: UMIN000012557

Sympathetic nervous system activation, arterial shear rate, and flow-mediated dilation

The aim of this study was to examine the contribution of arterial shear to changes in flow-mediated dilation (FMD) during sympathetic nervous system (SNS) activation in healthy humans. Ten healthy men reported to our laboratory four times. Bilateral FMD, shear rate (SR), and catecholamines were examined before/after 10-min of -35-mmHg lower body negative pressure (LBNP10). On day 1, localized forearm heating (LBNP10+heat) was applied in one limb to abolish the increase in retrograde SR associated with LBNP. Day 2 involved unilateral cuff inflation to 75 mmHg around one limb to exaggerate the LBNP-induced increase retrograde SR (LBNP10+cuff). Tests were repeated on days 3 and 4, using 30-min interventions (i.e., LBNP30+heat and LBNP30+cuff). LBNP10 significantly increased epinephrine levels and retrograde SR and decreased FMD (all P < 0.05). LBNP10+heat prevented the increase in retrograde SR, whereas LBNP10+cuff further increased retrograde SR (P < 0.05). Heating prevented the decrease in percent FMD (FMD%) after LBNP10 (interaction effect, P < 0.05), whereas cuffing did not significantly exaggerate the decrease in FMD% (interaction effect, P > 0.05). Prolongation of the LBNP stimulus for 30-min normalized retrograde SR, catecholamine levels, and FMD (all P > 0.05). Attenuation of retrograde SR during 30 min (LBNP30+heat) was associated with increased FMD% (interaction effects, P < 0.05), whereas increased retrograde SR (LBNP30+cuff) diminished FMD% (interaction effects, P < 0.05). These data suggest that LBNP-induced SNS stimulation decreases FMD, at least in part due to the impact of LBNP on arterial shear stress. Prolonged LBNP stimulation was not associated with changes in SR or FMD%. Our data support a role for changes in SR to the impact of SNS stimulation on FMD.

Abstract P432: Effects of Weight Management by Exercise Mode on Subclinical Atherosclerosis for Women with Abdominal Obesity: A Randomized Controlled Trial

Purpose: Few studies have examined differential effects of weight management by exercise mode on subclinical atherosclerosis. We hypothesized that exercise modes of aerobic, resistance, and combination exercises would have differential effects on endothelial dysfunction, aortic stiffness, and carotid intima-media thickness (IMT) in a weight management intervention. Methods: We conducted a randomized controlled trial in which 110 sedentary women with abdominal obesity were enrolled in a 12-month weight management program between September 2010 and November 2011. Fifty participants were randomly assigned to an aerobic training group, 30 to a resistance training group, and 30 to a combined aerobic and resistance training group. The weight management had a diet-alone intervention for the first 3 months and a diet-plus-exercise intervention for the next 9 months according to exercise modes. Exercise training was designed for three days per week in 60-minute sessions and a gradual increase in exercise intensity using % heart rate reserve. Flow-mediated dilation (FMD), carotid-femoral pulse wave velocity (PWV), and carotid IMT were measured at 0, 3, 6, 9, and 12 months. Results: Participants had a mean age of 43.1 years and a mean body mass index of 28.5 kg/m 2 . After a 12-month intervention, participants experienced a weight loss of approximately 5%. Changes in FMD, PWV, and IMT did not differ significantly by exercise mode, but PWV and IMT were significantly reduced over the diet-plus-exercise intervention. Conclusion: Among women with abdominal obesity, the effects of weight management on subclinical atherosclerosis did not differ by exercise mode, but its effects on aortic stiffness and carotid IMT may be beneficial over time.

Brachial artery flow-mediated dilatation and carotid intima medial thickness in pediatric nephrotic syndrome: a cross-sectional case–control study

Children with nephrotic syndrome (NS) have hyperlipidemia, which may lead to endothelial dysfunction. This study evaluated endothelial function and structural atherosclerosis in NS children with disease duration more than 2 years, by assessment of brachial artery flow-mediated dilatation (FMD) and carotid intima medial thickness (CIMT). This is a cross-sectional case-control study recruiting 32 subjects aged 1-13 years with NS and 32 matched controls. Clinical details, FMD and CIMT were recorded. Lipid profile and oxidative stress were also analyzed in the subjects. The proportionate change in FMD was significantly lower in cases (5.65 ± 6.08 %) compared to controls (15.21 ± 9.41 %) (p < 0.01). No significant differences in CIMT were observed (p = 0.383). Blood malondialdehyde was significantly higher (p = 0.006) in the cases. Overall, 25 NS children (78 %) were in remission for more than 6 months, and in them, 9 (36 %) had deranged lipid profile. On stepwise linear regression, age of the patient was found to be a determinant of FMD (model R (2) = 18.9 %, p value = 0.048). The significantly low proportionate change in FMD in NS children suggests an ongoing process of endothelial dysfunction. Further studies are needed to confirm these findings. A long-term follow-up of children with NS may be required for identification of CIMT derangements.

Brachial artery diameter has a predictive value in the improvement of flow-mediated dilation after aortic valve replacement for aortic stenosis

Aortic stenosis (AS) is the most common valvular disease and aortic valve replacement (AVR) is one of its most effective interventions. AS affects not only the left ventricle, but also vascular function beyond the stenotic valve, which can lead to various types of vascular dysfunction. However, research evaluating the effect of AS on aortic vascular function is limited. In this study, we investigated clinical meaning to evaluate endothelial function in subjects with AS. From April 2011 to April 2012, 20 consecutive adult patients with degenerative AS (mean age, 74.7 ± 7.4 years; range 50-83 years) who underwent AVR at our institution were included in the study. We measured flow-mediated dilation (FMD) to evaluate the effect of AS on endothelial function. The difference between brachial artery diameter (BAD) before (4.0 ± 0.7 mm) and after AVR (3.9 ± 0.6 mm) was not significant (p = 0.043), but FMD significantly improved after AVR (from 3.1 ± 1.8 to 6.0 ± 2.7 %, p < 0.0001). We also analyzed FMD × BAD index, endogenous vasodilatory capability independent of BAD, resulting that it also significantly increased after AVR (12.3 ± 7.0-22.5 ± 9.3, p < 0.0001). We divided patients into two groups by pre- to post-AVR change in FMD (ΔFMD); large-ΔFMD group [ΔFMD >3.0 % (median value)] and small-ΔFMD group (ΔFMD <3.0 %). There were no significant changes in age, blood pressure, heart rate, B-type natriuretic peptide, or echocardiographic parameters in either group. In contrast, BAD was significantly larger in the small ΔFMD group (4.3 ± 0.7 mm) than in the large ΔFMD group (3.7 ± 0.7 mm) (p = 0.030). In addition, cardio-thoracic ratio was significantly greater in the small ΔFMD group (58.4 ± 7.1 %) than in the large ΔFMD group (53.7 ± 4.6 %) (p = 0.048). Receiver operating characteristic curve analysis of BAD to differentiate large and small ΔFMD demonstrated an area under the curve of 0.750 (p = 0.059) and that optimal cutoff for BAD was 4.28 mm (70 % sensitivity, 80 % specificity). AVR in subjects with AS is associated with a significant improvement in FMD in the brachial artery. Measurement of the BAD may be helpful in distinguishing whether the impairment of FMD in AS derives from a stenotic valve or vascular remodeling.

Effect of niacin on endothelial function: A systematic review and meta-analysis of randomized controlled trials

Endothelial dysfunction is an independent predictor of incident atherosclerotic cardiovascular disease (ACVD). Niacin possesses high-density lipoprotein (HDL)-elevating, antioxidant and anti-inflammatory properties, all potentially contributing to the amelioration of endothelial function. However, controversies exist among trials reporting the effects of niacin on endothelium-dependent flow-mediated dilation (FMD) as a reliable surrogate of endothelial function. The objective of this study was to assess the effect of niacin on brachial artery FMD using a meta-analysis of available evidence. MEDLINE and Scopus databases were searched for randomized controlled trials investigating the impact of niacin therapy on brachial artery FMD. Meta-analysis of eligible studies was conducted using a random-effects model. Pooled effects were measured by weighted mean difference (WMD) and 95% confidence intervals (CIs). Quality assessment, and subgroup, meta-regression and sensitivity analyses were conducted using standard methods. Among 596 citations, 19 full-text articles were read and seven were found to be eligible for inclusion. Eligible studies involved 441 subjects comprising 228 in the niacin and 213 in the control groups. Niacin therapy significantly improved FMD (WMD: 1.98%; 95% CI: 0.91-3.05%; p = 0.0003) and this effect was robust in the sensitivity analysis. The effect size was greater in the subgroup of studies administering higher doses of niacin (≥ 2000 mg/day) as well as those studies administering niacin for primary prevention of ACVD. Meta-regression indicated no association between niacin-induced changes in FMD and changes in plasma HDL-cholesterol, low-density lipoprotein-cholesterol or triglycerides. None of the included studies could find any significant effect of niacin on nitroglycerin-mediated dilation. In conclusion, treatment with niacin improves endothelial function.

Acute impact of retrograde shear rate on brachial and superficial femoral artery flow-mediated dilation in humans.

Retrograde shear rate (SR) in the brachial artery (BA) is associated with endothelial dysfunction; a precursor to atherosclerosis. The BA does not typically manifest clinical atherosclerosis, whereas the superficial femoral artery (SFA) is more prone to developing plaque. Examine whether the impact of incremental levels of retrograde SR differs between atherosclerosis‐prone (i.e., SFA) and ‐resistant vessels (i.e., BA) in healthy men. Thirteen healthy young men reported three times to the laboratory. We examined BA flow‐mediated dilation (FMD) before and after 30‐min exposure to cuff inflation around the forearm at 0, 30, and 60 mmHg, to manipulate retrograde SR. Subsequently, the 30‐min intervention was repeated in the SFA, using the same cuff pressure as in the forearm. Order of testing (vessel and intervention) was randomized among subjects. We found a dose‐dependent increase in retrograde SR with 30 and 60 mmHg cuff inflation, which was present in both the BA and SFA (all P < 0.05). BA and SFA FMD decreased after the 30‐min intervention (“time”: P = 0.012), and this was dependent on cuff pressure (“cuff × time”: P = 0.024). A significant decrease in FMD was observed after 60 mmHg only and this change was similarly present in both arteries (“time × artery”: P = 0.227). Moreover, the BA and SFA demonstrate a similar relationship between changes in retrograde SR and FMD (r = 0.498 and 0.475, respectively). Our study demonstrates that acute exposure to an increase in retrograde shear leads to comparable decreases in FMD in atherosclerotic‐prone and ‐resistant conduit arteries in humans.

The relationship between epicardial adipose tissue and endothelial dysfunction in patients with type 2 diabetes mellitus

Epicardial adipose tissue (EAT) has been shown to be related to cardiovascular risk. The aim of the present study was to investigate the relationship between EAT and endothelial function in patients with type 2 diabetes mellitus (DM). Type 2 DM patients were divided into two groups according to their brachial flow-mediated dilatation (FMD) values. The endothelial dysfunction (ED) group consisted of 46 patients with FMD change of <7%, while 46 patients with FMD change of >7% were accepted as the non-ED group. EAT thickness was measured on the right ventricular free wall from the transthoracic echocardiographic parasternal long- and short-axis views. The patients' demographic, anthropometric and laboratory findings were recorded. The mean diameter of EAT was 8.0±1.8 cm in the ED group and 6.6±1.2 cm in the non-ED group (p<0.001). The HbA1c levels were significantly higher in the ED group than non-ED group (8.55 [7.30-9.80], 7.45 [6.50-9.30], respectively; p=0.042). There were a negative correlation between FMD values and EAT (r=-0.437, p<0.001). The FMD values were weakly and negatively correlated with DM duration and HbA1c levels (r=-0.216, p=0.038; r=-0.266, p=0.010, respectively). EAT thickness was strongly correlated with body mass index (BMI) and waist length (r=0.405, p<0.001; r=0.515, p<0.001, respectively). The neutrophil count was significantly higher in the ED group than in the non-ED group. In multivariate logistic regression analysis, HbA1c and EAT diameters were found as predictors of ED in type 2 DM (odds ratio (OR): 1.887, 95% confidence interval (CI): 1.298-2.743, p=0.001; OR: 1.485, 95% CI: 1.054-2.093). EAT thickness predicts ED in patients with type 2 DM.

A reduction of 3 g/day from a usual 9 g/day salt diet improves endothelial function and decreases endothelin-1 in a randomised cross_over study in normotensive overweight and obese subjects

Background and aimIt is unclear if a modest reduction in dietary salt intake has beneficial effects on vascular function. The aim was to compare the effects of 9 g salt/day with 6 g salt/day intake on measures of vascular function and explore mechanisms of effect in overweight and obese adults. MethodsTwenty-five overweight/obese subjects (BMI 27–40 kg/m2) completed a randomised cross-over study of 6 weeks each on a reduced salt (RS) (6 g/day) and usual salt diet (US) (9 g/day). Flow-mediated-dilatation (FMD), 24 h blood pressure (BP), augmentation index (AIx), pulse wave velocity (PWV), plasma and urinary nitrate/nitrite, asymmetric dimethylarginine (ADMA), renin, aldosterone and endothelin-1 and vascular adhesion molecules were measured after 2 days and 6 weeks. Adherence to the diets was determined from two 24 h urine collections. ResultsUrinary sodium excretion was 155 ± 58 mmol/24 h US vs 113 ± 45 mmol/24 h RS (p = 0.002). Following the RS diet there was a significant improvement in FMD from 3.5 ± 2.8% to 5.6 ± 2.8% (P < 0.001) and decrease in serum endothelin-1 from 1.45 ± 0.38 pg/ml to 1.25 ± 0.39 pg/ml (P < 0.05). Endothelium-independent vasodilatation was also significantly different between treatments (P < 0.05). AIx, PWV, serum ADMA and plasma and urinary nitrate/nitrite concentrations were not different between treatments. Change in FMD was related to the urinary sodium: creatinine ratio (r = −0.47, P < 0.05) and was independent of blood pressure. Aldosterone and renin were unchanged. ConclusionsA small reduction in dietary salt intake of 3 g/day improves endothelial function in normotensive overweight and obese subjects. This response may be mediated by serum endothelin-1. This small reduction in salt had no effect on aldosterone and renin concentrations.This trial was registered with the Australian and New Zealand Clinical Trials Registry Unique Identifier: ACTRN12609000321246 http://www.anzctr.org.au/ACTRN12609000321246.aspx

Lipid Lowering Therapy with Combination of Niacin and Statin in Women: Age-Related Endothelial Effects

Background. Many women remain at risk for cardiac events despite treatment to reduce low-density lipoprotein cholesterol (LDL-C). We hypothesized that for postmenopausal women treated with niacin in addition to statin vascular function will improve. Methods. We conducted a randomized, double-blind, placebo-controlled trial of 16 weeks of niacin (N) versus placebo (PL) in 43 women (mean age, 67±9 years) previously on statin therapy. Study outcomes included lipoprotein levels, vascular inflammation assessed by high sensitivity C-reactive protein (hsCRP), interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), and endothelial function, assessed as brachial artery flow mediated dilation (FMD). Results. The N group significantly increased HDL-C and decreased LDL-C cholesterol relative to PL (both P&lt;0.01). FMD improved in both groups (P=0.02) irrespective of niacin (P=0.21). Age influenced change in FMD (P=0.01) such that improved FMD (before to after) with lipid lowering therapy was greater with older age (P=0.03 Pearson correlation = 0.34), independent of treatment group. Conclusions. Lipid lowering therapy with combination of niacin and statin does not improve inflammation or endothelial function compared to statin alone. However, older women demonstrate relatively greater endothelial benefit of lipid lowering therapy over 4 months. This trial is registered with Clinicaltrials.gov NCT00590629.

Plasma Adropin Levels Predict Endothelial Dysfunction Like Flow-Mediated Dilatation in Patients With Type 2 Diabetes Mellitus

ObjectiveThis study investigated the role of plasma adropin levels to show endothelial dysfunction in individuals with type 2 diabetes mellitus and to compare these with flow-mediated dilatation.MethodsA total of 92...

Effects of Nonlinear Aerobic Training on Erectile Dysfunction and Cardiovascular Function Following Radical Prostatectomy for Clinically Localized Prostate Cancer

Erectile dysfunction (ED) is a major adverse effect of radical prostatectomy (RP). We conducted a randomized controlled trial to examine the efficacy of aerobic training (AT) compared with usual care (UC) on ED prevalence in 50 men (n=25 per group) after RP. AT consisted of five walking sessions per week at 55–100% of peak oxygen uptake (VO2peak) for 30–60min per session following a nonlinear prescription. The primary outcome was change in the prevalence of ED, as measured by the International Index of Erectile Function (IIEF), from baseline to 6 mo. Secondary outcomes were brachial artery flow–mediated dilation (FMD), VO2peak, cardiovascular (CV) risk profile (eg, lipid profile, body composition), and patient-reported outcomes (PROs). The prevalence of ED (IIEF score ≤21) decreased by 20% in the AT group and by 24% in the UC group (difference: p=0.406). There were no significant between-group differences in any erectile function subscale (p>0.05). Significant between-group differences were observed for changes in FMD and VO2peak, favoring AT. There were no group differences in other markers of CV risk profile or PROs. In summary, nonlinear AT does not improve ED in men with localized prostate cancer in the acute period following RP. Trial registrationClinicaltrials.gov identifier NCT00620932.

Change In Flow Mediated Dilation After Transfusion Is Dependent On BMI and Blood Age

Blood transfusions are given for acute and chronic illness including cardiothoracic surgery, acute stabilization, and chronic transfusion therapy (CTT) in patients with thalassemia and sickle cell disease (SCD). Increased age of stored red blood cells and the associated storage lesion has been implicated in poor cardiovascular outcomes, increased length of ICU stay, multiorgan failure and increased use of inotropes after cardiac surgery. Red cell aging, during storage, is thought to alter the metabolic profile of the red cell in a manner that causes decreased nitric oxide bioavailability. Aged red cells demonstrate vasoinhibitory activity of aortic ring preparations. S-nitrosohemoglobin is decreased in stored blood but when replete, tissue oxygen delivery and renal damage were ameliorated in an animal blood loss model. We aimed to determine whether the age of the stored blood relates to vascular function in-vivo, using a population of chronically transfused patients with SCD.We did prospective study to examine transfusion effects on vascular function, in which we enrolled 26 patients with SCD on CTT and tested flow mediated dilation (FMD) of the brachial artery, cardiac output and blood viscosity changes with transfusion. We measured both oxygenated and deoxygenated whole blood viscosity at shear rates from 1s-1 to 1000s-1 at native hematocrit using a Rheolog viscometer (Rheologics Co). We also obtained pre and post transfusion measures of cardiac output, flow mediated dilation of the brachial artery, blood counts, chemistry panels, markers of inflammation and hemolysis.14 females and 12 males were enrolled. The ages and reasons for starting transfusions were similar for male and female patients. As expected, transfusion resulted in significant increases of hemoglobin and hematocrit (hct) with concomitant decrease of hemoglobin S% (HbS%) and reticulocyte count. Male patients had a significantly higher HbS%, reticulocyte count, plasma free hemoglobin and platelet count compared to females. Viscosity increased significantly across all shear rates with transfusion and with deoxygenation. There was no sex difference in viscosity. FMD was significantly improved following transfusion with an average increase of 1.4% (P=0.01). By univariate analysis, elevated body mass index (BMI), small change in hematocrit to viscosity ratio (HVR) at 2s-1 (low shear), and the lower age of the stored blood were significantly associated with improved FMD. By multivariate analysis, using only two variables at a time due to small sample size, elevated BMI was the best predictor of improved FMD. (Figure 1) There was a confounding effect between the age of the blood and BMI in our study; there was a negative correlation between age of the blood given and BMI, whereby smaller patients received older blood in our cohort.(R2 0.20, P=0.03). BMI did not correlate with pre-transfusion FMD. [Display omitted] Most patients with SCD on CTT had improved FMD following transfusion and given the dependence of FMD on shear stress, changes in rheologic factors such as viscosity and hematocrit would be expected to cause significant changes in FMD. The increase in hct, and viscosity and the decrease in HbS% did not correlate with improvement in FMD. Decrease in low shear HVR did correlate with improved FMD, however, FMD is thought to correlate with higher shear rates, whereas the HVR at low shear rate would be found in the venous system. This could provide a link between endothelial function and the low shear venous system, particularly due to its FMD correlation with “deoxygenated” HVR. BMI and age of the stored red cells correlated whereby our smaller patients received older blood resulting in confounding between these variables. Despite the confounding effect, when blood age was locked in the model, BMI still exerts an independent effect on FMD. Whether the effect of BMI is chronic or acute could not be determined in our study; however, nutritional factors, adipose tissue and hormones might play a role in the set point of FMD via eNOS expression in the endothelium. Older blood age was associated with worsening FMD, which is consistent with decreased nitric oxide bioavailability as a piece of the red cell storage lesion puzzle. Future studies should attempt to control for BMI and blood age to minimize confounding effects. Disclosures:Coates:Novartis Inc.: Honoraria, Speakers Bureau; Apopharma: Honoraria, Speakers Bureau; Shire: Speakers Bureau. Wood:Shire: Consultancy, Research Funding; Apopharma: Honoraria, Patents & Royalties; Novartis: Honoraria.