Improvement In Flow-mediated Dilation Research Articles

Endothelial dysfunction in acute and long standing COVID−19: A prospective cohort study

BackgroundCoronavirus disease-19 (COVID-19) is implicated by active endotheliitis, and cardiovascular morbidity. The long-COVID-19 syndrome implications in atherosclerosis have not been elucidated yet. We assessed the immediate, intermediate, and long-term effects of COVID-19 on endothelial function. MethodsIn this prospective cohort study, patients hospitalized for COVID-19 at the medical ward or Intensive Care Unit (ICU) were enrolled and followed up to 6 months post-hospital discharge. Medical history and laboratory examinations were performed while the endothelial function was assessed by brachial artery flow-mediated dilation (FMD). Comparison with propensity score-matched cohort (control group) was performed at the acute (upon hospital admission) and follow-up (1 and 6 months) stages. ResultsSeventy-three patients diagnosed with COVID-19 (37% admitted in ICU) were recruited. FMD was significantly (p < 0.001) impaired in the COVID-19 group (1.65 ± 2.31%) compared to the control (6.51 ± 2.91%). ICU-treated subjects presented significantly impaired (p = 0.001) FMD (0.48 ± 1.01%) compared to those treated in the medical ward (2.33 ± 2.57%). During hospitalization, FMD was inversely associated with Interleukin-6 and Troponin I (p < 0.05 for all). Although, a significant improvement in FMD was noted during the follow-up (acute: 1.75 ± 2.19% vs. 1 month: 4.23 ± 2.02%, vs. 6 months: 5.24 ± 1.62%; p = 0.001), FMD remained impaired compared to control (6.48 ± 3.08%) at 1 month (p < 0.001) and 6 months (p = 0.01) post-hospital discharge. ConclusionCOVID-19 patients develop a notable endothelial dysfunction, which is progressively improved over a 6-month follow-up but remains impaired compared to healthy controls subjects. Whether chronic dysregulation of endothelial function following COVID-19 could be accompanied by a residual risk for cardiovascular and thrombotic events merits further research.

Impact of ALLopurInol on ENdothelial funCtion in diabEtic patients affected with coronary artery disease: ALLIENCE trial

Allopurinol, a xanthine oxidase inhibitor, was shown to be useful in improving endothelial dysfunction in diabetic patients independently from their coronary status. We sought to assess the impact of allopurinol on endothelial function in diabetic patients with coronary artery disease (CAD) reputed to have severe endothelial dysfunction. We performed a simple-blind randomized trial enrolling patients with type 2 diabetes and CAD who underwent percutaneous coronary intervention. Patients were randomly assigned to either conventional optimal medical therapy alone (control group) or optimal medical therapy associated with high dose of allopurinol: 300 mg daily the first month then 600 mg daily the second month (allopurinol group). Endothelial function was assessed by flow-mediated dilation (FMD). The primary endpoint was the changes in FMD (Δ FMD) at 2 months. The secondary endpoints were the changes in endothelium-independent brachial dilation, and quality of life (QoL) as assessed by the Seattle Angina Questionnaire. A total of 64 patients (mean age 58.5 ± 8.3 years, 84.1% males) were randomly assigned to either allopurinol group ( n = 32) and control group ( n = 32). At baseline, FMD was comparable between the two groups ( P = 0.961). At 2 months, no significant change was observed in FMD between allopurinol group and control group ( P = 0.709). Regarding QoL, patients in allopurinol group showed better improvement in angina frequency ( P = 0.020) and disease perception ( P < 0.001) than controls. Subgroups analysis revealed that allopurinol was associated with significant improvement in FMD only in patients with poorly controlled diabetes (HBA1c > 8%) ( P = 0.010) and those with acid uric serum level ≤ 287 μmol/L ( P = 0.010) ( Fig. 1 ). Although allopurinol improved QoL (particularly angina frequency) in CAD diabetic patients, it did not improve the endothelial function except in those with poorly controlled diabetes and low acid uric serum level.

Comparison of high intensity interval training with standard cardiac rehabilitation on vascular function.

To compare the short- and long-term effects of high-intensity interval training (HIIT) with usual care moderate intensity continuous training (MICT) on systemic vascular function and stiffness in patients with coronary artery disease undergoing a cardiac rehabilitation program. Randomized controlled trial. Fifty-four patients (age=63±8years, 93% male) were randomized to complete 3sessions/week (2supervised, 1home-based) of either (1) 4×4-min HIIT or (2) 40-min MICT, for 4weeks. Patients then continued 3 unsupervised home-based sessions/week of their allocated training for 11months. Brachial artery flow-mediated dilation, pulse wave velocity, and blood pressure were measured at baseline, 4weeks, 3months, 6months, and 12months. Data were analyzed using linear mixed modeling and are presented as mean change from baseline (95% CI). HIIT showed a greater improvement in flow-mediated dilation compared to MICT after 4weeks [1.5% (0.9, 2.1) vs 0.1% (-0.5, 0.8); p=0.004) but not 12months [1.2% (-0.2, 2.5) vs 0.4% (-0.8, 1.7); p=0.153). There were no short- or long-term group differences for changes in pulse wave velocity, peripheral or central blood pressure between HIIT and MICT after 4weeks, or over 12months. A 4-week HIIT program was superior to MICT for improving vascular function, but not arterial stiffness or blood pressure. Over 12months, changes in vascular function, blood pressure, and arterial stiffness were similar for HIIT and MICT.

Effects of indulgent food snacking, with and without exercise training, on body weight, fat mass, and cardiometabolic risk markers in overweight and obese men.

We hypothesized that exercise training would prevent gains in body weight and body fat, and worsening of cardiometabolic risk markers, during a 4‐week period of indulgent food snacking in overweight/obese men. Twenty‐eight physically inactive men (ages 19–47 yr) with body mass index (BMI) ≥25 kg/m2 consumed 48 donuts (2/day, 6 days/week; ~14,500 kcal total) for 4 weeks while maintaining habitual diet. Men were randomly assigned to control (n = 9), moderate‐intensity continuous training (MICT; n = 9), or high‐intensity interval training (HIIT; n = 10). Exercise training occurred 4 days/week, ~250 kcal/session. Controls did not increase body weight, body fat, or visceral abdominal fat. This was partially explained by a decrease in self‐reported habitual energy (−239 kcal/day, p = 0.05) and carbohydrate (−47 g/day; p = 0.02) intake. Large inter‐individual variability in changes in body weight, fat, and fat‐free mass was evident in all groups. Fasting blood pressure, and blood concentrations of glucose, insulin, and lipids were unchanged in all groups. Glucose incremental area under the curve during an oral glucose tolerance test was reduced by 25.6% in control (p = 0.001) and 32.8% in MICT (p = 0.01) groups. Flow‐mediated dilation (FMD) was not changed in any group. VO2max increased (p ≤ 0.001) in MICT (9.2%) and HIIT (12.1%) groups. We conclude that in physically inactive men with BMI ≥25 kg/m2, consuming ~14,500 kcal as donuts over 4 weeks did not adversely affect body weight and body fat, or several markers of cardiometabolic risk. Consumption of the donuts may have prevented the expected improvement in FMD with HIIT.

Effect of melatonin supplementation on endothelial function in heart failure with reduced ejection fraction: A randomized, double‐blinded clinical trial

BackgroundThis study aimed to investigate the effect of melatonin supplementation on endothelial function in patients with heart failure with reduced ejection fraction (HFrEF).MethodsThis is an analysis of the MeHR trial, a randomized double‐blinded placebo‐controlled clinical trial with two parallel arms of 1:1. Oral 10 mg melatonin tablets or placebo was administered for 24 weeks. Deference in the percentage of flow‐mediated dilatation (FMD) after the intervention was the primary outcome.ResultsNinety‐two patients were included in the study (age: 62.7±10.3 years, 87.0% male, ejection fraction (EF): 28.6±8.1). After adjustment for baseline FMD and age, a statistically significant difference in post‐treatment FMD in favor of the melatonin group was seen (estimated marginal means [95%CI], melatonin: 7.84% [6.69–8.98], placebo: 5.98% [4.84–7.12], p = .027). There was no significant difference in the mean of post‐treatment systolic/diastolic blood pressure, serum total antioxidant capacity, and serum malondialdehyde (MDA) between groups. Subgroup analysis showed significant improvement in FMD and MDA in the melatonin group in nondiabetic patients, while no difference was seen between study groups in diabetic patients.ConclusionsMelatonin supplementation in HFrEF might improve endothelial function; however, this beneficial effect might not be seen in diabetic patients.

Effects of structured home-based exercise training on circulating endothelial progenitor cells and endothelial function in patients with intermittent claudication.

Exercise training improves walking capacity in patients with intermittent claudication (IC). Endothelial progenitor cells (EPCs), endothelial microparticles (EMPs), and endothelial dysfunction could play a role in this process. We measured EPCs and EMPs in a group of 60 patients with IC, and in a control group of 20 individuals without IC, before a treadmill test and 2, 24, and 48 hours after the test. Thirty patients with IC were randomly assigned to perform a 12-week home-based exercise training program. The EPC count, flow-mediated dilation (FMD) of the brachial artery, pain-free walking time (PFWT), and maximum walking time (MWT) were measured at the baseline and after the exercise training program. In patients with IC, EMPs significantly increased 2 hours after the treadmill test, whereas EPCs significantly increased after 24 hours. Among the subjects assigned to complete the training program, we observed a significant increase in the number of EPCs after 12 weeks, as well as an improvement in FMD, PFWT, and MWT. A significant correlation between the variation of EPCs, FMD, and MWT was found. The increase of EPCs and FMD were independent determinants of the walking capacity improvement, without significant interaction. Our results suggest that EPCs mobilization contributes to the improvement of walking capacity in patients with IC undergoing structured physical training. A number of different, partly independent, mechanisms are involved in this process, and our results highlight the potential role of EMPs release and endothelial function improvement. ClinicalTrials.gov Identifier: NCT04302571.

Effect of Serum Urate Lowering With Allopurinol on Blood Pressure in Young Adults: A Randomized, Controlled, Crossover Trial.

To determine whether serum urate reduction with allopurinol lowers blood pressure (BP) in young adults and the mechanisms mediating this hypothesized effect. We conducted a single-center, randomized, double-blind, crossover clinical trial. Adults ages 18-40 years with baseline systolic BP ≥120 and <160 mm Hg or diastolic BP ≥80 and <100 mm Hg, and serum urate ≥5.0 mg/dl for men or ≥4.0 mg/dl for women were enrolled. Main exclusion criteria included chronic kidney disease, gout, or past use of urate-lowering therapies. Participants received oral allopurinol (300 mg daily) or placebo for 1 month followed by a 2-4 week washout and then were crossed over. Study outcome measures were change in systolic BP from baseline, endothelial function estimated as flow-mediated dilation (FMD), and high-sensitivity C-reactive protein (hsCRP) levels. Adverse events were assessed. Ninety-nine participants were randomized, and 82 completed all visits. The mean ± SD age was 28.0 ± 7.0 years, 62.6% were men, and 40.4% were African American. In the primary intent-to-treat analysis, systolic BP did not change during the allopurinol treatment phase (mean ± SEM -1.39 ± 1.16 mm Hg) or placebo treatment phase (-1.06 ± 1.08 mm Hg). FMD increased during allopurinol treatment periods compared to placebo treatment periods (mean ± SEM 2.5 ± 0.55% versus -0.1 ± 0.42%; P < 0.001). There were no changes in hsCRP level and no serious adverse events. Our findings indicate that urate-lowering therapy with allopurinol does not lower systolic BP or hsCRP level in young adults when compared with placebo, despite improvements in FMD. These findings do not support urate lowering as a treatment for hypertension in young adults.

Acute Effect of Heat Exposure on Brachial Artery FMD: Impact of Modality and Measurement Timeline

Introduction Heat exposure is receiving a lot of attention for its potential to improve endothelial function, as measured by brachial artery flow-mediated dilation (FMD). Although most intervention studies have observed an improvement in brachial artery FMD, the acute effect of heat exposure has been inconsistent. This observation likely stems from the various modalities employed (local limb heating to whole-body heating) and the timing of FMD measurement following the heating intervention (immediately after up to 60 min post-heating). Identifying a heating modality that consistently improves brachial artery FMD and establishing the timeline of the response would facilitate investigations into potential mechanisms mediating heat-induced improvements in brachial artery FMD without the need of more challenging intervention studies. The aims of this study are to 1) determine the acute effect of four heating interventions on brachial artery FMD, and 2) characterize the time-dependent changes in brachial artery FMD following each intervention. Methods On separate days, 11 young and healthy adults (3F/8M; 29±6 y; 66.5±9.4 kg; 1.7±0.1 m) were exposed to: i) 10 minutes of forearm heating using an electric blanket (EB); ii) 30 minutes of forearm heating in 40˚C water (WI); iii) 60 minutes of whole-body heating where the arm used to assess brachial artery FMD was not covered by the water perfused suit (WHB-U), or; iv) was covered for the entire 60 minutes of whole-body heating with the suit (WBH-C). During each trial, brachial artery FMD was measured prior to the heating intervention (baseline), within 5 minutes following the end of the intervention, and every 30 minutes for two hours following the intervention. Results Mean shear rate increased from baseline during the WI (+78±43 s-1, P=0.02), WBH-U (+177±99 s-1, P<0.01) and WBH-C (+140±43 s-1, P<0.01) interventions, but not during EB (+18±35 s-1, P=0.37). Brachial artery FMD was unaffected by the EB intervention (P=0.39). Conversely, there was a main effect of time for FMD during the WI (P=0.03), WBH-U (P<0.01), and WBH-C (P<0.01) interventions. Specifically, FMD was greater relative to baseline, 90 minutes following the WI intervention (+3.7±3.3%, P=0.03, increase in 8/11 participants). A lower FMD relative to baseline was observed within 5 minutes of the end of the WBH-U (-4.5±3.7%, P<0.01, decrease in 9/11 participants) and WBH-C (WBH-C: -6.1±3.5%, P<0.01, decrease in 10/11 participants) interventions. Conclusion These results suggest that 10 minutes of local heating with an electric blanket may not modulate brachial FMD, whereas whole-body heating with or without local heating of the arm causes a temporary reduction in FMD. Forearm immersion in 40°C water for 30 minutes was the only intervention that consistently improved brachial artery FMD, but only when measured 90 minutes following the intervention.

The impact of standing desks on cardiometabolic and vascular health.

Sedentary behavior is associated with cardiovascular disease (CVD) and mortality, independent of physical activity. The biological mechanisms underlying these associations are largely unknown. We hypothesized that obese subjects with sedentary desk jobs, when assigned a sit-stand desk, will reduce daily sedentary time, and show improvement in arterial flow-mediated dilation (FMD), an early indicator of CVD. Overweight and obese subjects without known CVD were recruited at our institution and given an adjustable sit-stand desk at work. Activities were quantified with an accelerometer for 7 days at baseline and during the intervention. FMD of the brachial and superficial femoral arteries, fasting lipids, insulin and glucose labs, and anthropometrics were measured at baseline, and 12 and 24 weeks. Repeated one-way ANOVA tests were used to compare measurements over time. Fifteen participants were enrolled (93% female, mean age 40 ± 5 years, mean body mass index [BMI] 33 ± 5). Mean daily sedentary time at work decreased by 90 minutes from baseline (385 ± 49 minutes) to 12 weeks (297 ± 80 minutes, p = 0.002) and 24 weeks (295 ± 127 minutes, p = 0.015). Femoral FMD increased from baseline (4.9 ± 1.7%) to 12 weeks (6.4 ± 2.3%, p = 0.043) and further to 24 weeks (8.1 ± 3.2%, p = 0.009). Significant improvement in fasting triglycerides and insulin resistance occurred. There was no change in brachial FMD, exercise activity, step counts, weight, or BMI. A significant reduction in sedentary time during working hours was identified with utilization of a sit-stand desk and sustained over 24 weeks. Improvements in FMD, triglycerides, and insulin resistance provide insight into mechanisms of adverse health risks associated with sedentary behavior.

Noninvasive ventilation acutely improves endothelial function in exacerbated COPD patients

PurposeAcute exacerbation of chronic obstructive pulmonary disease (AECOPD) is associated with an elevated risk of cardiovascular events, which can be linked to endothelial dysfunction. In this study, we aimed to investigate whether noninvasive ventilation (NIV) acutely changes endothelial function in hospitalized AECOPD patients. MethodsTwenty-one AECOPD patients were assessed in a hospital ward setting from 24 to 48 h after admission. NIV was applied using a ventilator with bilevel pressure support. Before and after NIV protocol, patients were evaluated regarding (1) endothelium-dependent function, assessed non-invasively using the flow-mediated dilation (FMD) method; (2) arterial blood gas analysis. Other baseline evaluations included clinical and anthropometric data, and laboratory tests. ResultsThe total group showed a significant improvement in FMD as a result of NIV effect (P = 0.010). While arterial carbon dioxide and oxygen were not altered, oxygen saturation increased after NIV (P = 0.045). The subgroup comparison of responders (FMD ≥ 1%) and non-responders (FMD < 1%) showed significant baseline differences in body mass index (BMI) (P = 0.019) and predicted forced expiratory volume in one second (FEV1) (P = 0.007). In univariate and multivariate analyses, both BMI and FEV1 were determinant for endothelial response to NIV. ConclusionNIV acutely improves endothelial function in hospitalized AECOPD patients. Overweight and COPD severity may represent important characteristics for the magnitude of peripheral vascular response.

Effects of anti-inflammatory treatment and surgical intervention on endothelial glycocalyx, peripheral and coronary microcirculation and myocardial deformation in inflammatory bowel disease patients

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): EOMIFNE (Hellenic Society of IBD study) Introduction IBD alter gastrointestinal physiology and mucosal immunity through a complex inflammatory process which leads to significant arterial endothelial dysfunction and modification of cardiac structure and function. This study is performed to test the hypothesis that treatment with TNF-a inhibitor or surgical intervention improves cardiovascular function through anti-inflammatory mechanisms. Methods 57 IBD patients (45 CD and 12 UC, 40 ± 8 years, 57% male) were examined at baseline and 4 months after pharmaceutical (antiTNF-a) or surgical intervention. Subjects with a history of established cardiovascular risk factors were excluded. We measured a) carotid-femoral pulse wave velocity (PWV - Complior SP ALAM) and augmentation index (AI), b) flow mediated dilatation (FMD) of the brachial artery), c) perfused boundary region (PBR) of the sublingual arterial microvessels, d) LV longitudinal strain (GLS) and (PWV/GLS) as a marker of ventricular-arterial coupling, e) peak LV twisting, peak twisting velocity (pTwVel) and peak untwisting velocity (pUtwVel) using speckle tracking echocardiography, f) mitral annulus velocities by tissue doppler imaging (S’ and E’) and mitral inflow velocity (E), g) coronary flow reserve (CFR) by Doppler echocardiography, h) C-reactive protein (CRP), white blood cells (WBC). IBD severity was quantified using Mayo score and Harvey-Bradshaw Index (HBI) for UC and CD respectively. Results At baseline, the disease severity score and the WBC values were significantly correlated with peripheral PWV (r = 0.3, p &amp;lt; 0.05 and r = 0.364, p &amp;lt; 0.05), while central arterial AI was associated with median arterial pressure (r = 0.479, p &amp;lt; 0.05), lateral and septal mitral E’ velocity (r=-0.651, p &amp;lt; 0.05 and r=-0.587, p &amp;lt; 0.05). Four months after treatment, there was a reduction of CRP (13 ± 2.8 mg/L vs 3.9 ± 1.2 mg/L, p &amp;lt; 0.05), CFR (2.5 ± 0.08 vs 3.1 ± 0.11, p &amp;lt; 0.05) and PBR5-25 (2.27 ± 0.06 vs 2.09 ± 0.05 μm, p &amp;lt; 0.05) more significantly in pharmaceutical group (p &amp;lt; 0.05 vs p = 0.23). Moreover, there was an improvement of GLS (-18.6 ± 0.37 vs -20 ± 0.34, p &amp;lt; 0.05), LS-4ch (-18.3 ± 0.47 vs -19.3 ± 0.41, p &amp;lt; 0.05), GcircS (-18.1 ± 0.7 vs -20.1 ± 0.9, p &amp;lt; 0.05) and FMD (7.2%±0.6 vs 11.8%±1.4, p &amp;lt; 0.05). Moreover, there was an overall improvement of PWV/GLS (-0.49 ± 0.02 vs -0.43 ± 0.02, p &amp;lt; 0.05). It was greater after with anti-TNFa therapy compared to surgery (p &amp;lt; 0.05 vs p = 0.1) and particular for the GLS component (p &amp;lt; 0.05 vs p = 0.07). The difference in PBR5-25 was significantly correlated with the difference in GLS (r=-0.403, p &amp;lt; 0.05) and PWV/GLS (r = 0.421, p &amp;lt; 0.05). Conclusion IBD severity is associated with vascular and diastolic dysfunction, with significant improvement after anti-inflammatory treatment. Systemic anti-TNFa inhibition leads to significant improvement in myocardial deformation, endothelial and coronary microcirculatory function compared with local intestinal surgical intervention, possibly through a systemic reduction of excess inflammatory burden.

Effect of soy protein containing isoflavones on endothelial and vascular function in postmenopausal women: a systematic review and meta-analysis of randomized controlled trials.

The beneficial role of soy protein in cardiovascular health has been well documented in observational studies. However, evidence from clinical trials on effects of soy protein on endothelial function in postmenopausal women has been conflicting. We aimed to systematically review and conduct a meta-analysis of randomized controlled trials (RCTs) investigating the impact of soy protein supplement containing isoflavones on endothelial function in postmenopausal women. We searched PubMed-Medline, SCOPUS, Embase, and Google Scholar until March 2020 to find RCTs evaluating the impact of soy protein supplementation on endothelial function parameters. Random effects model (using DerSimonian-Laird method) was applied to synthesize quantitative data. We performed the leave-one-out method for sensitivity analysis. To quantitatively assess heterogeneity, the I index was applied. From a total of 267 studies identified from the initial search 15 and 5 studies were considered appropriate for inclusion into the systematic review and meta-analysis, respectively. In the meta-analysis, an insignificant enhancement in flow-mediated dilation (FMD) after soy protein supplementation (0.882%; 95% CI: -1.059 to 2.822; P = 0.373) was found. However, subgroup analysis showed that supplementation of isolated soy protein had significant effect on FMD (3.39%; 95% CI: 0.733-6.01; P = 0.01). Our findings suggest that soy protein supplementation does not lead to meaningful improvement in FMD in postmenopausal women. However, this finding is based on a limited number of studies. Additional high-quality large-scale RCTs are warranted.

Abstract 16926: The Effects of a Mitochondrial Targeted Ubiquinone (MitoQ) on Vascular Function in Chronic Kidney Disease

Introduction: Aberrant vascular function contributes to the substantially high cardiovascular burden of chronic kidney disease (CKD). Mitochondrial derived oxidative stress is a potential therapeutic target to ameliorate CKD related vascular dysfunction. Hypothesis: We hypothesized that a mitochondrial targeted antioxidant (MitoQ) would improve vascular function in Stage 3-5 CKD patients without overt cardiovascular disease. Methods: In this controlled, double-blind trial, 18 CKD patients (Mean±SEM: Age, 62±3 years; eGFR, 45±3 ml•min•1.73 2 ) were randomized to receive an oral dose of MitoQ (20mg/day; MTQ) or a Placebo (PLB) for 4 weeks. Outcome measures were assessed at week 0 and week 4. Aortic pressure waves were synthesized from brachial artery waveforms acquired by oscillometry and the use of a generalized transfer function. The central pressure waveform was separated into forward and reflected waves using a triangular flow waveform. Conduit artery vascular function was assessed via brachial artery flow mediated dilation (FMD). Results: MitoQ was well tolerated and patient compliance was high (MTQ, 99.6±0.4%; PLB, 97.8±2.2%). Independent of peripheral (Baseline vs. Follow Up: MTQ, 140±6 vs. 137±6 mmHg; PLB, 136±4 vs. 134±6 mmHg; interaction p=0.7) and central (MTQ, 128±5 vs. 123±6 mmHg; PLB, 124±3 vs. 123±5 mmHg; interaction p=0.8) systolic blood pressures, MitoQ maintained forward wave amplitudes (MTQ, 31±3 vs. 29±1 mmHg; PLB, 29±3 vs. 36±3 mmHg; interaction p=0.05) and tended to reduce reflected wave amplitudes (MTQ, 18±2 vs. 16±1 mmHg; PLB, 19±2 vs. 21±2 mmHg; interaction p=0.04). MitoQ administration favored improvements in FMD (MTQ, 2.4±0.3 vs. 4.0±0.9%; PLB, 4.2±1.0 vs. 2.5±1.0%; interaction p=0.04). Conclusions: These results suggest that targeting mitochondrial derived reactive oxygen species holds promise as a potential therapeutic strategy to improve CKD related vascular dysfunction. Whether MitoQ related improvements in arterial hemodynamics are a result of augmented cardiac function or a reduction in vascular resistance warrants future investigation in larger studies.

Dietary Approaches to Stop Hypertension Dietary Intervention Improves Blood Pressure and Vascular Health in Youth With Elevated Blood Pressure.

This randomized control trial assessed the post-intervention and 18-month follow-up effects of a 6-month dietary approaches to stop hypertension (DASH)-focused behavioral nutrition intervention, initiated in clinic with subsequent telephone and mail contact, on blood pressure (BP) and endothelial function in adolescents with elevated BP. Adolescents (n=159) 11 to 18 years of age with newly diagnosed elevated BP or stage 1 hypertension treated at a hospital-based clinic were randomized. DASH participants received a take-home manual plus 2 face-to-face counseling sessions at baseline and 3 months with a dietitian regarding the DASH diet, 6 monthly mailings, and 8 weekly and then 7 biweekly telephone calls focused on behavioral strategies to promote DASH adherence. Routine care participants received nutrition counseling with a dietitian consistent with pediatric guidelines established by the National High Blood Pressure Education Program. Outcomes, measured pre- and post-intervention and at 18-months follow-up, included change in BP, change in brachial artery flow-mediated dilation, and change in DASH score based on 3-day diet recalls. Adolescents in DASH versus routine care had a greater improvement in systolic BP (-2.7 mm Hg, P= 0.03, -0.3 z-score, P=0.03), flow-mediated dilation (2.5%, P=0.05), and DASH score (13.3 points, P<0.0001) from baseline to post-treatment and a greater improvement in flow-mediated dilation (3.1%, P=0.03) and DASH score (7.4 points, P=0.01) to 18 months. The DASH intervention proved more effective than routine care in initial systolic BP improvement and longer term improvement in endothelial function and diet quality in adolescents with elevated BP and hypertension. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00585832.

Short-term effects of maximal dynamic exercise on flow-mediated dilation in professional female soccer players.

Endothelial function assessment may provide important insights into the cardiovascular function and long-term effects of exercise training. Many studies have investigated the possible negative effects on cardiovascular function due to extreme athletic performance, leading to undesirable effects. The purposes of this study were to investigate the acute effects of maximal intensity exercise on endothelium-dependent vasodilation, and to understand the patterns of flow-mediated dilation (FMD) change following maximal exercise in elite female athletes with a high-volume training history. Twenty-six elite female soccer players (mean age, 22±4 years; BMI, 21±2 kg/m2; VO<inf>2max</inf>, 41±4 mL/kg/min) were evaluated. Brachial artery FMD was determined using high-resolution ultrasound at rest, and after 15 and 60 min of maximal cardiopulmonary exercise (CPX) testing on a treadmill. Flow velocity was measured at baseline and during reactive hyperemia at the same periods. Rest FMD was 12.4±5.5%. Peak diameter in response to reactive hyperemia was augmented after 15 min of CPX (3.5±0.4 vs. 3.6±0.4 mm, P<0.05), returning to resting values after 60 min. However, %FMD did not change among time periods. There were two characteristic patterns of FMD response following CPX. Compared to FMD at rest, half of the subjects responded with an increased FMD following maximum exercise (10.5±6.1 vs. 17.8±7.5%, P<0.05). The other subjects demonstrated a reduced FMD response following maximum exercise (14.2±4.3 vs. 10.9±3.2%, P<0.01). These results indicate that elite female soccer players presented robust brachial artery FMD at rest, with a heterogeneous FMD response to acute exercise with a 50% FMD improvement rate.

Reproducible improvement in endothelial function following two separate periods of high-intensity interval training in young men.

High-intensity interval training (HIIT) can improve vascular function, as assessed by brachial artery flow-mediated dilation (FMD). However, when separated by a period of detraining, the reproducibility of FMD responses to repeated periods of HIIT is unknown. The purpose of this study was to determine the group mean and intraindividual reproducibility of FMD responses to two 4-wk periods of HIIT, separated by 3 mo of detraining. Thirteen healthy, recreationally active men (21 ± 2 yr) completed the study. Each 4-wk HIIT period included 40 min of treadmill training four times/week. Each training session included four 7-min intervals: 4 min at 90%-95% heart rate maximum (HRmax) and 3 min at 70%-75% HRmax. Vascular (FMD) and cardiorespiratory fitness (maximal oxygen consumption [V̇o2max]) assessments were conducted before and following each 4-wk training period. Training resulted in significant improvements in V̇o2max (P < 0.001). Training also improved FMD (P < 0.001), with no differences between periods (P = 0.394), even after controlling for changes in baseline diameter and the shear rate stimulus. There was a significant, moderate relationship between the change in FMD in HIIT period 1 versus period 2 [R2 = 0.493, P = 0.011, intraclass correlation coefficient: 0.600, coefficient of variation: 17.3%]. Consecutive periods of HIIT separated by detraining resulted in similar improvements in FMD at the group level, and individual FMD changes in period 1 of HIIT predicted FMD changes in response to period 2. Considered alongside substantial between-participant variability in magnitude of FMD improvement, this suggests that there are reproducible, interindividual differences in the potential to improve vascular function with HIIT.NEW & NOTEWORTHY This is the first study examining endothelial function [flow-mediated dilation (FMD)] following repeated periods of high-intensity interval training (HIIT). Two periods of HIIT separated by detraining resulted in reproducible group-level improvements in FMD. Despite considerable between-subject variability in FMD adaptation, individual FMD changes with the first HIIT period predicted FMD changes in the second period. This indicates the existence of reproducible between-subject differences in susceptibility to FMD improvement with HIIT.

Predictors of endothelial function improvement in patients with mild hypertriglyceridemia without evidence of coronary artery disease treated with purified eicosapentaenoic acid

Background and aimsEicosapentaenoic acid (EPA) has been reported to reduce cardiovascular risk in patients with hypertriglyceridemia. Although several mechanisms underlying the effects of EPA have been demonstrated, those responsible for its beneficial role in patients with hypertriglyceridemia without evidence of coronary artery disease (CAD) have not been fully elucidated. We sought to clarify the main factors associated with EPA administration that led to improved endothelial function. MethodsForty-seven consecutive patients with mild hypertriglyceridemia (mean age, 59 ± 13 years) without evidence of CAD were prospectively enrolled and administered purified EPA (1800 mg/day). Forty-four patients who were not administered EPA were enrolled as age- and sex-matched controls. Clinical variables and flow-mediated dilation (FMD) were examined before and after 6 months of treatment. Univariate and multivariate regression analyses were performed between FMD changes and clinical variables. ResultsEPA treatment decreased triglyceride levels (from 224.6 ± 58.8 to 151.8 ± 54.5 mg/dl, p < 0.001) and increased FMD (from 4.21% ± 1.91% to 6.21% ± 2.30%, p < 0.001). Multivariate analysis showed that the change in FMD was associated with the baseline high-density lipoprotein cholesterol (HDL-C) level (β = −0.331, p = 0.027) and the change in EPA/arachidonic acid (AA) ratio (β = 0.301, p = 0.048). ConclusionsEPA treatment improved triglyceride levels and FMD in patients with mild hypertriglyceridemia and without evidence of CAD. The baseline HDL-C level and the change in EPA/AA ratio predicted FMD improvement. The beneficial effects of EPA on triglyceride-rich lipoproteins and vascular endothelium may help improve endothelial function.

High-Intensity Endurance and Strength Training in Water Polo Olympic Team Players: Impact on Arterial Wall Properties

Introduction: Regular physical activity is recommended to minimize health risk. However, the upper intensity threshold associated with the best health outcomes is difficult to be determined. Water polo (WP) Olympic athletes present unique characteristics such as high-intensity exercise, long training sessions, and a combination of endurance and strength training. Therefore, we examined in which way the long-term, intense, mixed endurance and strength training affects the peripheral and central hemodynamics. Methods: The study population consisted of 20 WP Olympic team players, 20 matched recreationally active (RA) subjects, and 20 sedentary control subjects (Cl). Reflected waves were assessed with the augmentation index (AIx), central aortic stiffness with pulse wave velocity (PWV), and endothelial function with flow-mediated dilation (FMD). Results: Amongst Cl subjects, RA subjects, and WP players, there was no difference in age (p = 0.33) as well as in brachial systolic pressure (p = 0.52), while there was a stepwise decrease in aortic systolic pressure (116 ± 16 mm Hg vs. 107 ± 14 mm Hg vs. 106 ± 6 mm Hg, p = 0.03). There was also a stepwise improvement in AIx (–4.22 ± 9.97% vs. –6.97 ± 11.28% vs. –12.14 ± 6.62%, p = 0.03) and FMD (6.61 ± 1.78% vs. 7.78 ± 1.98% vs. 8.3 ± 2.05%, p = 0.04) according to the intensity of exercise, with WP players having lower AIx and higher FMD compared to RA subjects and Cl subjects. No difference was found in PWV (Cl: 5.88 ± 0.72 m/s vs. RA: 6.04 ± 0.75 m/s vs. WP: 5.97 ± 1.09 m/s, p = 0.82) among the three studied groups. Conclusions: Young WP Olympic team players depict improved arterial wall properties and endothelial function compared to RA and Cl subjects.

Initiating guideline-concordant gout treatment improves arterial endothelial function and reduces intercritical inflammation: a prospective observational study

BackgroundPatients with gout have arterial dysfunction and systemic inflammation, even during intercritical episodes, which may be markers of future adverse cardiovascular outcomes. We conducted a prospective observational study to assess whether initiating guideline-concordant gout therapy with colchicine and a urate-lowering xanthine oxidase inhibitor (XOI) improves arterial function and reduces inflammation.MethodsThirty-eight untreated gout patients meeting American College of Rheumatology (ACR)/European League Against Rheumatism classification criteria for gout and ACR guidelines for initiating urate-lowering therapy (ULT) received colchicine (0.6 mg twice daily, or once daily for tolerance) and an XOI (allopurinol or febuxostat) titrated to ACR guideline-defined serum urate (sU) target. Treatment was begun during intercritical periods. The initiation of colchicine and XOI was staggered to permit assessment of a potential independent effect of colchicine. Brachial artery flow-mediated dilation (FMD) and nitrate-mediated dilation (NMD) assessed endothelium-dependent and endothelium-independent (smooth muscle) arterial responsiveness, respectively. High-sensitivity C-reactive protein (hsCRP), IL-1β, IL-6, myeloperoxidase (MPO) concentrations, and erythrocyte sedimentation rate (ESR) assessed systemic inflammation.ResultsFour weeks after achieving target sU concentration on colchicine plus an XOI, FMD was significantly improved (58% increase, p = 0.03). hsCRP, ESR, IL-1β, and IL-6 also all significantly improved (30%, 27%, 19.5%, and 18.8% decrease respectively; all p ≤ 0.03). Prior to addition of XOI, treatment with colchicine alone resulted in smaller numerical improvements in FMD, hsCRP, and ESR (20.7%, 8.9%, 13% reductions, respectively; all non-significant), but not IL-1β or IL-6. MPO and NMD did not change with therapy. We observed a moderate inverse correlation between hsCRP concentration and FMD responsiveness (R = − 0.41, p = 0.01). Subgroup analyses demonstrated improvement in FMD after achieving target sU concentration in patients without but not with established cardiovascular risk factors and comorbidities, particularly hypertension and hyperlipidemia.ConclusionsInitiating guideline-concordant gout treatment reduces intercritical systemic inflammation and improves endothelial-dependent arterial function, particularly in patients without established cardiovascular comorbidities.

MO049EFFECT OF VITAMIN D ON ENDOTHELIAL FUNCTION IN EARLY DIABETIC NEPHROPATHY

Abstract Background and Aims Diabetic Nephropathy is associated with endothelial dysfunction at an early stage. The benefit of Vitamin D supplementation on endothelial function is supported by a few studies in non-diabetic chronic kidney disease (CKD). However, studies on its effect in early DN is scarce. Hence, the present study was planned to assess the effect of vitamin D supplementation on endothelial function by measuring Flow mediated dilation (FMD) in patient of early DN. Method A total of 730 Diabetic subjects were screened for early DN based on Inclusion criteria (eGFR ≥ 120ml/min/1.73m2 with unrestricted ACR value eGFR of 60- 120 mL/min/1.73m2 and ACR 30-300mg) and Exclusion criteria (on ACE I or ARB, eGFR&amp;lt;60ml/min/1.73m2, Hypercalcemia (&amp;gt;11.5mg%), UTI, Pregnancy, Hypertension, HbA1c (&amp;gt;8.0 %), vitamin D supplementation during the last 6 month). Of them 103 included subjects were underwent randomization to receive either Cholecalciferol (54) or matching Placebo (49) in a double blind method. All were subjected to routine investigations, urinary albumin: creatinine (UACR), C reactive protein (CRP), serum 25(OH)vitamin D, intact parathyroid hormone (iPTH) and Flow mediated dilatation at the zero and six months. All subjects were subjected. Comparative results at zero and six months of both groups were compared and analyzed. Results There was no significant difference between cholecalciferol and placebo group with respect to CRP, iPTH, 25-hydroxyvitamin D (25(OH) D), UACR, FMD at baseline. Median FMD after 6 month was significantly higher in cholecalciferol as compared to placebo group [Median (IQR): 24 % (21.75-26.0) and 22% (18-24) respectively, p= 0.01]. After 6 month UACR was significantly lower in the cholecalciferol group as compared to placebo group (p= 0.04). Significant association of vitamin D level was observed with CRP level. In 25(OH) D &amp;lt; 20 ng/ml subgroup there was significant decrease in CRP level in comparison to 25(OH) D ≥20 ng/ml subgroup (p=0.04). Conclusion There was significant improvement in endothelial function as assessed by FMD% following vitamin D supplementation. Vitamin D supplementation given to early diabetic nephropathy patients may have favourable effects on cardiovascular outcome as reflected by improvement in FMD% and decrease in CRP level.