Acute Vascular Benefits of Finnish Sauna Bathing in Patients With Stable Coronary Artery Disease.

BACKGROUND: Finnish sauna bathing habits are associated with a decreased risk of cardiovascular mortality. The physiologic adaptations mediating this association remain to be fully elucidated. This study tested the hypothesis that Finnish sauna bathing acutely improves peripheral flow-mediated dilation (FMD) in middle-aged and older adults with stable coronary artery disease (CAD). METHODS: Twenty-two adults (20 male, 2 female; 67 ± 10 years) with stable CAD underwent 2 periods of 10 minutes in a Finnish sauna (81.3 ± 2.7°C, 23 ± 3% humidity) separated by 10 minutes of thermoneutral rest. Before and 51 ± 8 minutes after sauna bathing, brachial artery FMD and postocclusive reactive hyperemia (PORH) were evaluated by means of Doppler ultrasound. RESULTS: Sauna bathing increased core temperature (mean +0.66°C [95% CI 0.54-0.77], P < 0.01) and heart rate (+27 beats/min [24-29], P < 0.01), and decreased systolic (-19 mm Hg [-31 to -6]; P < 0.01) and diastolic (-6 mm Hg [-11 to -1], P < 0.01) blood pressures. Brachial artery FMD was greater after sauna bathing (+1.21% [0.16-2.26], P = 0.04), whereas PORH was unchanged (peak: +0.51 mL/min/mm Hg [-0.13 to 1.15], P = 0.11; area under the curve: +0.21 mL/mm Hg [-0.12 to 0.54]; P = 0.19). CONCLUSIONS: A typical Finnish sauna bathing session acutely improves peripheral FMD in middle-aged and older adults with stable CAD.

Effects of Beetroot Powder with or without L-Arginine on Postprandial Vascular Endothelial Function: Results of a Randomized Controlled Trial with Abdominally Obese Men.

BACKGROUND: Through effects on nitric oxide bioavailability, vascular endothelial function is improved after the intake of a high amount of nitrate or L-arginine, but decreased after the intake of a high-fat meal. Therefore, we compared the effects of beetroot powder with or without L-arginine on postprandial brachial artery flow-mediated vasodilation (FMD) after consumption of a high-fat mixed-meal. METHODS: Eighteen abdominally obese men completed this randomized, double-blinded, cross-over trial. The study consisted of five test days, each separated by a wash-out period of at least one week. Participants received in random order, a blended meal with a control or nutritional supplement consisting of beetroot powder providing 200 mg nitrate, beetroot with 0.8 g of L-arginine, beetroot with 1.5 g of L-arginine, or 3.0 g of L-arginine. Participants then fasted and 2 h postprandial FMD measurements were performed. RESULTS: No significant differences between meals were observed for postprandial FMD (p = 0.45) levels. However, there was a non-significant trend towards a more beneficial postprandial FMD response with the beetroot-containing meals as compared with meals without beetroot. CONCLUSION: This trial could not provide evidence for beneficial additive effects of a single dose of beetroot powder combined with L-arginine on postprandial endothelial function in abdominally obese men.

Ubiquinol Ameliorates Endothelial Dysfunction in Subjects with Mild-to-Moderate Dyslipidemia: A Randomized Clinical Trial.

In this randomized, double-blind, single-center trial (ANZCTR number ACTRN12619000436178) we aimed to investigate changes in endothelium-dependent vasodilation induced by ubiquinol, the reduced form of coenzyme Q10 (CoQ10), in healthy subjects with moderate dyslipidemia. Fifty-one subjects with low-density lipoprotein (LDL) cholesterol levels of 130-200 mg/dL, not taking statins or other lipid lowering treatments, moderate (2.5%-6.0%) endothelial dysfunction as measured by flow-mediated dilation (FMD) of the brachial artery, and no clinical signs of cardiovascular disease were randomized to receive either ubiquinol (200 or 100 mg/day) or placebo for 8 weeks. The primary outcome measure was the effect of ubiquinol supplementation on FMD at the end of the study. Secondary outcomes included changes in FMD on week 4, changes in total and oxidized plasma CoQ10 on week 4 and week 8, and changes in serum nitrate and nitrite levels (NOx), and plasma LDL susceptibility to oxidation in vitro on week 8. Analysis of the data of the 48 participants who completed the study demonstrated a significantly increased FMD in both treated groups compared with the placebo group (200 mg/day, +1.28% ± 0.90%; 100 mg/day, +1.34% ± 1.44%; p < 0.001) and a marked increase in plasma CoQ10, either total (p < 0.001) and reduced (p < 0.001). Serum NOx increased significantly and dose-dependently in all treated subjects (p = 0.016), while LDL oxidation lag time improved significantly in those receiving 200 mg/day (p = 0.017). Ubiquinol significantly ameliorated dyslipidemia-related endothelial dysfunction. This effect was strongly related to increased nitric oxide bioavailability and was partly mediated by enhanced LDL antioxidant protection.

Effect of α-linolenic acid on vascular function and metabolic risk markers during the fasting and postprandial phase: A randomized placebo-controlled trial in untreated (pre-)hypertensive individuals.

BACKGROUND: Only a limited number of studies have examined the vascular and postprandial effects of α-linolenic acid (ALA, C18:3n-3). Therefore, we performed a well-controlled trial focusing specifically on the effects of ALA on vascular function and metabolic risk markers during the fasting and postprandial phase in untreated (pre-)hypertensive individuals. METHODS: In a double-blind randomized, placebo-controlled parallel study, 59 overweight and obese adults (40 men and 19 women, aged 60 ± 8 years) with a high-normal blood pressure or mild (stage I) hypertension consumed daily either 10 g of refined cold-pressed flaxseed oil, providing 4.7 g ALA (n = 29), or 10 g of high-oleic sunflower (control) oil (n = 30) for 12 weeks. RESULTS: As compared with the high-oleic oil control, intake of flaxseed oil did not change brachial artery flow-mediated vasodilation, carotid-to-femoral pulse wave velocity, retinal microvascular calibers and plasma markers of microvascular endothelial function during the fasting and postprandial phase. Fasting plasma concentrations of free fatty acid (FFA) and TNF-α decreased by 58 µmol/L (P = 0.02) and 0.14 pg/mL (P = 0.03), respectively. No differences were found in other fasting markers of lipid and glucose metabolism, and low-grade systemic inflammation. In addition, dietary ALA did not affect postprandial changes in glucose, insulin, triacylglycerol, FFA and plasma inflammatory markers after meal intake. CONCLUSION: A high intake of ALA, about 3-5 times the recommended daily intake, for 12 weeks decreased fasting FFA and TNF-α plasma concentrations. No effects were found on other metabolic risk markers and vascular function during the fasting and postprandial phase in untreated high-normal and stage I hypertensive individuals.

Effects of Grape Seed Proanthocyanidin Extract on Vascular Endothelial Function in Participants with Prehypertension: A Randomized, Double-Blind, Placebo-Controlled Study.

This study aimed to investigate the effects of grape seed proanthocyanidin extract (GSPE) on blood pressure and vascular endothelial function in middle-aged Japanese adults with prehypertension. We conducted a randomized, double-blind, placebo-controlled study on 6 men and 24 women aged 40-64 years old. The participants were randomized to receive tablets containing either low-dose (200 mg/day) or high-dose (400 mg/day) GSPE, or placebo, for 12 weeks. Systolic and diastolic blood pressures (SBP and DBP, respectively), brachial flow-mediated dilation (FMD), and other cardiovascular parameters were measured before and after 4, 8, and 12 weeks of treatment. The mean SBP in the high-dose group significantly decreased by 13 mmHg after 12 weeks (P = 0.028), although FMD did not change. In an ad hoc analysis of non-smoking participants (n = 21), the mean SBP, DBP, stiffness parameter ß, distensibility, incremental elastic modulus (Einc), and pulse wave velocity (PWV) also significantly improved in the high-dose group after 12 weeks. Changes in Einc and PWV from baseline to 12 weeks were significantly greater in the high-dose group than in the placebo group (Einc, P = 0.023; PWV, P = 0.03). GSPE consumption could help maintain vascular elasticity and normal blood pressure in this population.

Acute effect of Finnish sauna bathing on brachial artery flow-mediated dilation and reactive hyperemia in healthy middle-aged and older adults.

Regular Finnish sauna bathing is associated with a reduced risk of all-cause and cardiovascular mortality in middle-aged and older adults. Potential acute physiological adaptations induced by sauna bathing that underlie this relationship remain to be fully elucidated. The purpose of this study was to determine if typical Finnish sauna sessions acutely improve brachial artery flow-mediated dilation (FMD) and reactive hyperemia (RH) in healthy middle-aged and older adults. Using a randomized crossover design, FMD and RH were evaluated in 21 healthy adults (66 ± 6 years, 10 men/11 women) before and after each of the following conditions: (1) 1 × 10 min of Finnish sauna bathing (80.2 ± 3.2°C, 23 ± 2% humidity); (2) 2 × 10 min of sauna bathing separated by 10 min of rest outside the sauna; (3) a time control period (10 min of seated rest outside the sauna). FMD was taken as the peak change from baseline in brachial artery diameter following 5 min of forearm ischemia, whereas RH was quantified as both peak and area-under-the-curve forearm vascular conductance postischemia. FMD was statistically similar pre to post 1 × 10 min (4.69 ± 2.46 to 5.41 ± 2.64%, P = 0.20) and 2 × 10 min of sauna bathing (4.16 ± 1.79 to 4.55 ± 2.14%, P = 0.58). Peak and area-under-the-curve forearm vascular conductance were also similar following both sauna interventions. These results suggest that typical Finnish sauna bathing sessions do not acutely improve brachial artery FMD and RH in healthy middle-aged and older adults.

Effect of acute high-phosphate intake on muscle metaboreflex activation and vascular function.

Increased consumption of inorganic phosphate (Pi), an abundant ingredient in processed foods, has been associated with elevated cardiovascular disease risk; however, studies investigating underlying mechanisms are limited. Recently, high dietary Pi was shown to exaggerate the pressor response to static muscle contraction in rodents in part because of overactivation of metabolically sensitive skeletal muscle afferents. Whether acute high Pi consumption affects muscle metaboreflex activation in humans remains unknown. Furthermore, although acute high Pi consumption has been shown to impair vascular function in young healthy men, equivocal results have been reported. Therefore, we hypothesized that acute high Pi consumption augments mean arterial pressure (MAP) responses during muscle metaboreflex activation, impairs endothelial function, and increases arterial stiffness in young healthy men. Subjects performed 35% maximal voluntary contraction static handgrip (HG), followed by postexercise ischemia (PEI) to isolate muscle metaboreflex activation. Resting flow-mediated dilation (FMD) and arterial stiffness were assessed. Measures were made before (pre) and 60 min after (post) subjects consumed either a high-phosphate drink (2,000 mg phosphorus and 1,520 mg sodium) or a sodium drink (1,520 mg sodium; control). MAP responses during HG (preΔ = +23 ± 3 mmHg; postΔ = +21 ± 2 mmHg; P = 0.101) and PEI (preΔ = +21 ± 4 mmHg; postΔ = +18 ± 3 mmHg; P = 0.184) were similar before and after Pi consumption. In contrast, FMD was significantly attenuated following Pi (pre = 5.1 ± 0.5%; post = 3.5 ± 0.5%; P = 0.010), whereas arterial stiffness remained unchanged. There were no changes in any measured variable after control drink consumption. In summary, although the muscle metaboreflex remains unaffected following acute high Pi consumption in young healthy men, endothelial function is impaired. NEW & NOTEWORTHY This study was the first to investigate the influence of acute high-phosphate consumption on the pressor response during isometric handgrip and isolated muscle metaboreflex activation during postexercise ischemia in young healthy humans. We demonstrated that a single high dose of phosphate (2,000 mg) did not augment blood pressure in response to exercise or isolated muscle metaboreflex activation, but endothelial function was blunted in young healthy men.

Montmorency cherry supplementation attenuates vascular dysfunction induced by prolonged forearm occlusion in overweight, middle-aged men.

Flavonoid supplementation improves brachial artery flow-mediated dilation (FMD), but it is not known whether flavonoids protect against vascular dysfunction induced by ischemia-reperfusion (IR) injury and associated respiratory burst. In a randomized, double-blind, placebo-controlled, crossover study, we investigated whether 4 wk supplementation with freeze-dried Montmorency cherry (MC) attenuated suppression of FMD after IR induced by prolonged forearm occlusion. Twelve physically inactive overweight, middle-aged men (52.8 ± 5.8 yr, BMI: 28.1 ± 5.3 kg/m2) consumed MC (235 mg/day anthocyanins) or placebo capsules for 4 wk, with supplementation blocks separated by 4 wk washout. Before and after each supplementation block, FMD responses and plasma nitrate and nitrite ([ NO2- ]) concentrations were measured at baseline and 15, 30, and 45 min after prolonged (20 min) forearm occlusion. FMD response was significantly depressed by the prolonged occlusion ( P < 0.001). After a 45-min reperfusion, FMD was restored to baseline levels after MC (ΔFMD presupplementation: -30.5 ± 8.4%, postsupplementation: -0.6 ± 9.5%) but not placebo supplementation (ΔFMD presupplementation: -11.6 ± 10.6, postsupplementation: -25.4 ± 4.0%; condition × supplement interaction: P = 0.038). Plasma [ NO2- ] decreased after prolonged occlusion but recovered faster after MC compared with placebo (Δ45 min to baseline; MC: presupplementation: -15.3 ± 9.6, postsupplementation: -6.2 ± 8.1; Placebo: presupplementation: -16.3 ± 5.9, postsupplementation: -27.7 ± 11.1 nmol/l; condition × supplement × time interaction: P = 0.033). Plasma peroxiredoxin concentration ([Prx2]) was significantly higher after MC (presupplementation: 22.8 ± 1.4, postsupplementation: 28.0 ± 2.4 ng/ml, P = 0.029) but not after placebo supplementation (presupplementation: 22.1 ± 2.2, postsupplementation: 23.7 ± 1.5 ng/ml). In conclusion, 4 wk MC supplementation enhanced recovery of endothelium-dependent vasodilatation after IR, in parallel with faster recovery of plasma [ NO2- ], suggesting NO dependency. These protective effects seem to be related to increased plasma [Prx2], presumably conferring protection against the respiratory burst during reperfusion. NEW & NOTEWORTHY This is the first study to demonstrate that 4 wk of Montmorency cherry powder supplementation exerted protective effects on endothelium-dependent vasodilation after transient ischemia-reperfusion injury in overweight, physically inactive, nonmedicated, hypertensive middle-aged men. These effects seem to be due to increased nitric oxide availability, as evidenced by higher plasma nitrite concentration and peak arterial diameter during the flow-mediated dilation measurement. This may be a consequence of increased concentration of peroxiredoxin and other antioxidant systems and, hence, reduced reactive oxygen species exposure.

The impact of acute mental stress on brachial artery flow-mediated dilation in women diagnosed with depression.

Endothelial function, assessed by flow-mediated dilation (FMD), may be transiently attenuated in healthy adults following acute mental stress. However, the impact of acute mental stress on endothelial function in the context of clinical depression is unknown. This study examined the impact of acute mental stress on FMD in women with a diagnosis of a depressive disorder. Forty-three otherwise healthy women (33 ±â€¯14 years) participated. Brachial artery diameter and blood velocity were assessed with ultrasound. FMD was assessed immediately prior to and 15 min following the Trier Social Stress Test (TSST). The FMD protocol included 5 min of forearm cuff occlusion (pressure = 250 mm Hg), followed by release. Shear stress was estimated by calculating shear rate (SR = brachial artery blood velocity/diameter). Stress reactivity was assessed via changes in mean arterial pressure (MAP), heart rate (HR) and salivary cortisol. Results are mean ±â€¯SD. A significant stress response was elicited by the TSST [MAP, HR and salivary cortisol increased (p < 0.05)]. Neither the SR stimulus nor FMD response differed pre-versus post-stress (p = 0.124 and p = 0.641, respectively). There was a modest negative correlation between cortisol reactivity and change in FMD from pre- to post-stress (R = -0.392, p = 0.011). To conclude, acute mental stress did not consistently impair endothelial function in women diagnosed with a depressive disorder; however, higher cortisol reactivity may increase the likelihood of post-stress endothelial dysfunction. Further research is required to better understand the factors influencing the relationship between acute mental stress, cortisol and endothelial function in women with depression.

Folic acid supplementation improves vascular endothelial function, yet not skin blood flow during exercise in the heat, in patients with heart failure.

Heart failure (HF) patients are susceptible to heat strain during exercise, secondary to blunted skin blood flow (SkBF) responses, which may be explained by impaired nitric oxide (NO)-dependent vasodilation. Folic acid improves vascular endothelial function and SkBF through NO-dependent mechanisms in healthy older individuals and patients with cardiovascular disease. We examined the effect of folic acid supplementation (5 mg/day for 6 wk) on vascular function [brachial artery flow-mediated dilation (FMD)] and SkBF responses [cutaneous vascular conductance (CVC)] during 60 min of exercise at a fixed metabolic heat production (300 WHprod) in a 30°C environment in 10 patients with HF (New York Heart Association Class I-II) and 10 healthy controls (CON). Serum folic acid concentration increased in HF [preintervention (pre): 1.4 ± 0.2; postintervention (post): 8.9 ± 6.7 ng/ml, P = 0.01] and CON (pre: 1.3 ± 0.6; post: 5.2 ± 4.9 ng/ml, P = 0.03). FMD improved by 2.1 ± 1.3% in HF ( P < 0.01), but no change was observed in CON postintervention ( P = 0.20). During exercise, the external workload performed on the cycle ergometer to attain the fixed level of heat production for exercise was similar between groups (HF: 60 ± 13; CON: 65 ± 20 external workload, P = 0.52). Increases in CVC during exercise were similar in HF (pre: 0.89 ± 0.43; post: 0.83 ± 0.45 au/mmHg, P = 0.80) and CON (pre: 2.01 ± 0.79; post: 2.03 ± 0.72 au/mmHg, P = 0.73), although the values were consistently lower in HF for both pre- and postintervention measurement intervals ( P < 0.05). These findings demonstrate that folic acid improves vascular endothelial function in patients with HF but does not enhance SkBF during exercise at a fixed metabolic heat production in a warm environment.

Low frequency electrical muscle stimulation and endothelial function in advanced heart failure patients.

AIM: Obtain initial estimates of the change in brachial artery endothelial function and maximal oxygen uptake (VO2peak ) with 8 weeks of low-frequency electrical muscle stimulation (LF-EMS) or sham in patients with advanced chronic heart failure. METHODS AND RESULTS: Using a double blind, randomized design, 35 patients with chronic heart failure (New York Heart Association class III-IV) were assigned to 8 weeks (5 × 60 min per week) of either LF-EMS (4 Hz, continuous) or sham (skin level stimulation only) of the quadriceps and hamstrings muscles. Four of the five sessions were at home and one under supervision. Ultrasound images of resting brachial artery diameter and post 5 min occlusion to determine flow-mediated dilation (FMD), a marker of vascular function and peak oxygen uptake (VO2peak ) during cardiopulmonary exercise test, were measured before and after LF-EMS (n = 20) and sham (n = 15) interventions. FMD improved by 2.56% (95% confidence interval: 0.69 to 3.80) with LF-EMS compared with sham (P = 0.07). There were no notable changes in VO2peak . CONCLUSIONS: Improvements in FMD with LF-EMS may have a clinically meaningful effect as higher FMD is associated with better prognosis. This is a preliminary finding, and a larger trial is warranted.

Differential influence of vitamin C on the peripheral and cerebral circulation after diving and exposure to hyperoxia.

We examined if the diving-induced vascular changes in the peripheral and cerebral circulation could be prevented by oral antioxidant supplementation. Fourteen divers performed a single scuba dive to eighteen meter sea water for 47 min. Twelve of the divers participated in a follow-up study involving breathing 60% of oxygen at ambient pressure for 47 min. Before both studies, participants ingested vitamin C (2 g/day) or a placebo capsule for 6 days. After a 2-wk washout, the study was repeated with the different condition. Endothelium-dependent vasodilator function of the brachial artery was assessed pre- and postintervention using the flow-mediated dilation (FMD) technique. Transcranial Doppler ultrasound was used to measure intracranial blood velocities pre- and 90 min postintervention. FMD was reduced by ∼32.8% and ∼21.2% postdive in the placebo and vitamin C trial and posthyperoxic condition in the placebo trial by ∼28.2% ( P < 0.05). This reduction in FMD was attenuated by ∼10% following vitamin C supplementation in the hyperoxic study ( P > 0.05). Elevations in intracranial blood velocities 30 min after surfacing from diving were reduced in the vitamin C study compared with the placebo trial ( P < 0.05). O2 breathing had no postintervention effects on intracranial velocities ( P > 0.05). Prophylactic ingestion of vitamin C effectively abrogated peripheral vascular dysfunction following exposure to 60% O2 but did not abolish the postdive decrease in FMD. Transient elevations of intracranial velocities postdive were reduced by vitamin C. These findings highlight the differential influence of vitamin C on peripheral and cerebral circulations following scuba diving, which are only partly mediated via hyperoxia.

Osteopathic manual therapy in heart failure patients: A randomized clinical trial.

BACKGROUND: Heart Failure (HF) patients usually present with increased arterial resistance and reduced blood pressure (BP) leading to an impaired functional capacity. Osteopathic Manual Therapy (OMT) focused on myofascial release techniques (MRT) and in the balancing of diaphragmatic tensions, has been shown to improve blood flow in individuals using the resistive index (RI). However, its effects in HF patients have not been examined. PURPOSE: To evaluate the acute response of selected osteopathic techniques on RI, heart rate (HR), and BP in patients with HF. METHODS: Randomized-controlled clinical trial of HF patients assigned to MRT (six different techniques with three aimed at the pelvis, two at the thorax, and one at the neck for 15 min) or Control group (subjects in supine position for 15 min without intervention). The RI of the femoral, brachial and carotid arteries was measured via doppler ultrasound while HR and BP were measured via sphygmomanometry before and after a single MRT or control intervention. RESULTS: Twenty-two HF patients equally distributed (50% male, mean age 53 years; range 32-69 years) (ejection fraction = 35.6%, VO2peak: 12.9 mL/kg-1 min-1) were evaluated. We found no intra or inter group differences in RI of the carotid (ΔMRT: 0.07% vs Δ Control:11.8%), brachial (ΔMRT:0.17% vs ΔControl: 2.9%), or femoral arteries (ΔMRT:1.65% vs ΔControl: 0.97%) (P > 0.05) and no difference in HR or BP (ΔMRT:0.6% vs ΔControl: 3%), (P > 0.05). CONCLUSION: A single MRT session did not significantly change the RI, HR, or BP of HF patients.

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

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

Treatment with omega-3 polyunsaturated fatty acids does not improve endothelial function in patients with type 2 diabetes and very high cardiovascular risk: A randomized, double-blind, placebo-controlled study (Omega-FMD).

BACKGROUND AND AIMS: Numerous recent studies conducted in different clinical settings have focused on the benefits of omega-3 polyunsaturated fatty acids (n-3 PUFAs) in the prevention of cardiovascular diseases. There is limited evidence that patients with type 2 diabetes (T2D) and very high cardiovascular risk can also benefit from a high dose of n-3PUFAs, especially those on optimal medical therapy as recommended by the guidelines. The aim of the present study was to assess the impact of high-dose n-3 PUFA treatment on endothelial function in patients with T2D and established atherosclerotic cardiovascular disease (ASCVD). METHODS: We conducted a prospective randomized double-blind, placebo-controlled, 2-center study, in which endothelial function was measured using flow-mediated dilation (FMD) and nitroglycerin-mediated dilation (NMD). Serum fatty acids composition was measured by gas chromatography. All measurements were done at baseline and after 3 months of treatment with PUFAs at a dose of 2 g/d (n = 36) or placebo (n = 38). RESULTS: The majority of the study population was treated with optimal medical therapy. Despite significantly higher concentrations of eicosapentaenoic acid (EPA) and docosahexaenoic acid in the n-3 PUFA group after 3-month treatment, we did not observe significant changes in endothelial function indices (FMD and NMD). However, in regression analysis, only baseline FMD was associated with EPA concentration before 3 months of n-3 PUFA treatment. CONCLUSIONS: Three months of high-dose n-3 PUFA treatment in very high-risk patients with ASCVD and T2D did not improve the endothelial function indices.

Vitamin D supplementation improves endothelial dysfunction in patients with non-dialysis chronic kidney disease.

PURPOSE: Hypovitaminosis D is common in chronic kidney disease (CKD) and is associated with endothelial dysfunction and cardiovascular events. This study aimed to investigate the effects of vitamin D supplementation on endothelial dysfunction in non-dialysis CKD patients. MATERIALS AND METHODS: Seventy-one non-dialysis CKD patients with low vitamin D (serum 25(OH)D < 30 ng/mL) were recruited. Patients received oral cholecalciferol 50,000 units once a week for 12 weeks. Changes in endothelial function by brachial artery flow-mediated dilation (FMD), soluble vascular cell adhesion molecule-1 (sVCAM-1), and sE-selectin were studied. RESULTS: There was a significant increase in serum levels of 25(OH)D after cholecalciferol supplementation (33.7 ± 12.1 vs. 13.2 ± 5.4 ng/mL, P < 0.001). Multivariable regression analysis showed that higher proteinuria (ß = - 0.548, P < 0.001) and lower levels of 25(OH)D (ß = 0.360, P < 0.001) at baseline were related to lower 25(OH)D level after supplementation. FMD increased significantly from 4.4 ± 1.3 to 5.1 ± 1.5% (P < 0.001), and soluble endothelial biomarkers decreased: sVCAM-1 from 926.9 ± 158.0 to 867.0 ± 129.0 ng/mL (P < 0.001), and sE-selectin 69.7 ± 15.8 to 63.3 ± 14.7 ng/mL (P < 0.001). CONCLUSIONS: Vitamin D supplementation can improve endothelial dysfunction in pre-dialysis CKD patients.

Effect of Monthly, High-Dose, Long-Term Vitamin D Supplementation on Central Blood Pressure Parameters: A Randomized Controlled Trial Substudy.

BACKGROUND: The effects of monthly, high-dose, long-term (≥1-year) vitamin D supplementation on central blood pressure (BP) parameters are unknown. METHODS AND RESULTS: A total of 517 adults (58% male, aged 50-84 years) were recruited into a double-blinded, placebo-controlled trial substudy and randomized to receive, for 1.1 years (median; range: 0.9-1.5 years), either (1) vitamin D3 200 000 IU (initial dose) followed 1 month later by monthly 100 000-IU doses (n=256) or (2) placebo monthly (n=261). At baseline (n=517) and follow-up (n=380), suprasystolic oscillometry was undertaken, yielding aortic BP waveforms and hemodynamic parameters. Mean deseasonalized 25-hydroxyvitamin D increased from 66 nmol/L (SD: 24) at baseline to 122 nmol/L (SD: 42) at follow-up in the vitamin D group, with no change in the placebo group. Despite small, nonsignificant changes in hemodynamic parameters in the total sample (primary outcome), we observed consistently favorable changes among the 150 participants with vitamin D deficiency (<50 nmol/L) at baseline. In this subgroup, mean changes in the vitamin D group (n=71) versus placebo group (n=79) were -5.3 mm Hg (95% confidence interval [CI], -11.8 to 1.3) for brachial systolic BP (P=0.11), -2.8 mm Hg (95% CI, -6.2 to 0.7) for brachial diastolic BP (P=0.12), -7.5 mm Hg (95% CI, -14.4 to -0.6) for aortic systolic BP (P=0.03), -5.7 mm Hg (95% CI, -10.8 to -0.6) for augmentation index (P=0.03), -0.3 m/s (95% CI, -0.6 to -0.1) for pulse wave velocity (P=0.02), -8.6 mm Hg (95% CI, -15.4 to -1.9) for peak reservoir pressure (P=0.01), and -3.6 mm Hg (95% CI, -6.3 to -0.8) for backward pressure amplitude (P=0.01). CONCLUSIONS: Monthly, high-dose, 1-year vitamin D supplementation lowered central BP parameters among adults with vitamin D deficiency but not in the total sample. CLINICAL TRIAL REGISTRATION: URL: http://www.anzctr.org.au. Unique identifier: ACTRN12611000402943.

Cholecalciferol, Calcitriol, and Vascular Function in CKD: A Randomized, Double-Blind Trial.

BACKGROUND AND OBJECTIVES: High circulating vitamin D levels are associated with lower cardiovascular mortality in CKD, possibly by modifying endothelial function. We examined the effect of calcitriol versus cholecalciferol supplementation on vascular endothelial function in patients with CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We performed a prospective, double-blind, randomized trial of 128 adult patients with eGFR=15-44 ml/min per 1.73 m2and serum 25-hydroxyvitamin D level <30 ng/ml at the University of Colorado. Participants were randomly assigned to oral cholecalciferol (2000 IU daily) or calcitriol (0.5 µg) daily for 6 months. The primary end point was change in brachial artery flow-mediated dilation. Secondary end points included changes in circulating markers of mineral metabolism and circulating and cellular markers of inflammation. RESULTS: One hundred and fifteen patients completed the study. The mean (SD) age and eGFR of participants were 58±12 years old and 33.0±10.2 ml/min per 1.73 m2, respectively. There were no significant differences between groups at baseline. After 6 months, neither calcitriol nor cholecalciferol treatment resulted in a significant improvement in flow-mediated dilation (mean±SD percentage flow-mediated dilation; calcitriol: baseline 4.8±3.1%, end of study 5.1±3.6%; cholecalciferol: baseline 5.2±5.2%, end of study 4.7±3.6%); 25-hydroxyvitamin D levels increased significantly in the cholecalciferol group compared with the calcitriol group (cholecalciferol: 11.0±9.5 ng/ml; calcitriol: -0.8±4.8 ng/ml; P<0.001). Parathyroid hormone levels decreased significantly in the calcitriol group compared with the cholecalciferol group (median [interquartile range]; calcitriol: -22.1 [-48.7-3.5] pg/ml; cholecalciferol: -0.3 [-22.6-16.9] pg/ml; P=0.004). CONCLUSIONS: Six months of therapy with calcitriol or cholecalciferol did not improve vascular endothelial function or improve inflammation in patients with CKD.

Effects of Intradialytic Neuromuscular Electrical Stimulation on Strength and Muscle Architecture in Patients With Chronic Kidney Failure: Randomized Clinical Trial.

This study aimed to evaluate the effects of neuromuscular electrical stimulation (NMES) on muscle strength and architecture, functional capacity, and endothelial function in patients with chronic kidney failure (CKF) on hemodialysis (HD). Twenty-one patients with CKF on HD were randomized into a control group (CG; n = 10) and neuromuscular electrical stimulation group (NMESG; n = 11) who received NMES in the quadriceps muscle for 8 weeks, 3 times/week (20-34 min) during HD sessions. The muscle strength of the lower limbs was evaluated by dynamometry and sit-and-stand test (SST); muscle architecture through ultrasonography; functional capacity by the distance covered in a 6-min walk test and the endothelial function by flow-mediated dilatation technique of the brachial artery. There was an increase in the strength of the lower limbs in the NMESG compared to the CG (dynamometry: 43.28 ± 16.94 vs. 35.84 ± 16.89, P = 0.006; SST: 16.10 ± 6.51 vs. 12.50 ± 4.7, P = 0.029). There was a significant reduction in pennation angles of the right vastus lateralis (RVL) and left vastus lateralis (LVL) in the CG when compared to the NMESG (RVL: 11.93 [10.70-15.11] vs. 13.57 [11.81-15.96], P = 0.039; LVL: 11.62 [9.00-14.20] vs. 15.52 [12.86-20.02], P = 0.042). There was no change in functional capacity and in the endothelial function for CG and NMESG, respectively. In conclusion, NMES increases muscle strength and has a protective effect against muscle atrophy of the lower limbs of patients with chronic kidney failure on HD.