Flow-mediated Vasodilation Research Articles

Diagnostic Criteria of Flow‐Mediated Vasodilation for Normal Endothelial Function and Nitroglycerin‐Induced Vasodilation for Normal Vascular Smooth Muscle Function of the Brachial Artery

BackgroundDiagnostic criteria of flow‐mediated vasodilation (FMD), an index of endothelial function, and nitroglycerin‐induced vasodilation (NID), an index of vascular smooth muscle function, of the brachial artery have not been established. The purpose of this study was to propose diagnostic criteria of FMD and NID for normal endothelial function and normal vascular smooth muscle function.Methods and ResultsWe investigated the cutoff values of FMD and NID in subjects with (risk group) and those without cardiovascular risk factors or cardiovascular diseases (no‐risk group) in 7277 Japanese subjects (mean age 51.4±10.8 years) from the Flow‐Mediated Dilation Japan study and the Flow‐Mediated Dilatation Japan Registry study for analysis of the cutoff value of FMD and in 1764 Japanese subjects (62.2±16.1 years) from the registry of Hiroshima University Hospital for analysis of the cutoff value of NID. Receiver‐operator characteristic curve analysis of FMD to discriminate subjects in the no‐risk group from patients in the risk group showed that the optimal cutoff value of FMD to diagnose subjects in the no‐risk group was 7.1%. Receiver‐operator characteristic curve analysis of NID to discriminate subjects in the no‐risk group from patients in the risk group showed that the optimal cutoff value of NID to diagnose subjects in the no‐risk group was 15.6%.ConclusionsWe propose that the cutoff value for normal endothelial function assessed by FMD of the brachial artery is 7.1% and that the cutoff value for normal vascular smooth muscle function assessed by NID of the brachial artery is 15.6% in Japanese subjects.Clinical Trial Registration http://www.umin.ac.jp Unique identifiers: UMIN000012950, UMIN000012951, UMIN000012952, and UMIN000003409

Flow-Mediated Vasodilatation which is diagnostic method of endothelial dysfunctions change in atrial septal defect patients before and after closure of the ASD

Aim: Atrial septal defect secondary pulmonary hypertension causes disruption of the endothelial structure, resulting in an increase in vasoconstrictor mediators and a decrease in vasodilator mediators. These changes on the endothelial system alter the flow in the pulmonary vein and the systemic vein bed. This also has an effect on flow mediated vasodilatation. Our purpose in this study is to evaluate the endothelial dysfunction after atrial septal defect closure via flow mediated vasodilatation. Material and Methods: Total 51 patients with pre and one mount after post treatment secundum-type atrial septal defect and 40 healthy volunteers were prospectively enrolled. Atrial septal defect was treated with transcathater closure procedure. Flow mediated vasodilatation was measured to evaluate endothelial function prior to and one month after the defect was closured.Results: Flow-mediated vasodilatation values were significantly higher in an atrial septal defect′s patient than in the healthy volunteer (11.2 ± 1.01 m/s vs. 12.7 ± 1.18 m/s, P 0.001). Flow-mediated vasodilatation values were significantly reduced at the follow-up one month after the procedure compared to baseline. Moreover, there was a significant negative correlation between pulmonary arterial pressure values and flow-mediated vasodilatation (r=-0.347; p=0.013) in the pretreatment group.Conclusion: Flow-mediated vasodilatation values were significantly lower in the right cardiac chambers, and the systolic pulmonary arterial pressure was improved. This result has shown us that atrial septal defect closure may benefit from endothelial dysfunction.

Association of YKL-40 with endothelial dysfunction in patients with essential hypertension

Human cartilage glycoprotein 39 (YKL-40) is related with presence and extent of atherosclerosis, which can be a new biomarker of inflammation and endothelial dysfunction. The relationship between YKL-40 and endothelial dysfunction in patients with essential hypertension (EH) has not been intensively investigated. The relationship between serum level of YKL-40 and endothelial dysfunction was evaluated in 60 EH subjects and 50 normal control (NEH) subjects. Enzyme-linked immunosorbent assay (ELISA) was used to measure serum levels of YKL-40. Brachial artery flow-mediated vasodilation (FMD) was used to measure endothelial-dependent nitric oxide-mediated vasodilatory capacity as the function of endothelial index. This study demonstrated that YKL-40 expression was significantly increased ( p < 0.05) in EH subjects compared with NEH subjects. The FMD was significantly impaired in EH subjects compared with NEH subjects. YKL-40 was not only negatively correlated with FMD, but also with carotid artery intima-media thickness (IMT). Multiple liner regression analysis identified that YKL-40 was independent of FMD development. The level of YKL-40 was elevated in EH patients and inversely related with FMD and may be independent of endothelial dysfunction in EH.

Pre-Impaired Fasting Glucose State Is a Risk Factor for Endothelial Dysfunction: Flow-Mediated Dilation Japan (FMD-J) Study

Background: Diabetes mellitus is associated with endothelial dysfunction. However, there is little information on the relationships of fasting blood glucose (FBG) including high normal blood glucose and impaired fasting glucose (IFG) with endothelial function. The purpose of this study was to evaluate the relationship between FBG level and flow-mediated vasodilation (FMD) in detail using a large sample size. Methods: This study was a cross-sectional study. We measured FMD in 7265 subjects at 31 general hospitals. The subjects were divided into four groups based on FBG levels: <5·55 mmol/L, 5·55-6·05 mmol/L, 6·11-6·94 mmol/L, and ≥6·99 mmol/L or known diabetes. The subjects were also divided into six groups based on FBG levels: <5·00 mmol/L, 5·00-5·22 mmol/L, 5·27-5·50 mmol/L, 5·55-6·05 mmol/L, 6·11-6·94 mmol/L, and ≥6·99 mmol/L or known diabetes. Findings: FMD decreased in relation to increase in FBG level. There was a significant difference in FMD between the FBG of <5·55 mmol/L group and the other three groups (6·7±3·1% vs. 5·9±2·8%, 5·7±3·1%, and 5·1±2·6%; p<0·0001, respectively). After adjustment for confounding factors, the odds of having the lowest quartile of FMD was significantly higher in the FBG of 5·27-5·50 mmol/L, 5·55-6·05 mmol/L, 6·11-6·94 mmol/L, and ≥6·99 mmol/L or known diabetes groups than in the FBG of <5·00 mmol/L group. Interpretation: These findings suggest that FBG of 5·55-6·05 mmol/L and FBG of 6·11-6·94 mmol/L are similarly associated with endothelial dysfunction and that a pre-IFG state (FBG of 5·27-5·50 mmol/L) is also a risk for endothelial dysfunction compared with FBG of <5·00 mmol/L. Funding Statement: Grant-in-Aid for Scientific Research from the Ministry of Education, Science and Culture of Japan (18590815 and 21590898 to Y.Higashi) and a Grant-in-Aid of Japanese Arteriosclerosis Prevention Fund (to Y.Higashi). Declaration of Interests: All authors have no conflicts of interests to report. Ethics Approval Statement: The Ethics Committee of Hiroshima University approved the study protocol. Written informed consent for participation in this study was obtained from all participants.

Flow-Mediated Vasodilation and Reactive Hyperemia Index in Heart Failure with Reduced or Preserved Ejection Fraction.

Vascular endothelial dysfunction is part of the underlying pathophysiology of heart failure. However, there are no reports in which vascular endothelial function of both conduit arteries and microvasculature was assessed in patients with heart failure. This study was aimed to assess vascular endothelial function separately in heart failure with reduced (HFrEF) and preserved ejection fraction (HFpEF). We performed simultaneous measurement of both flow-mediated vasodilation for endothelial function of conduit arteries and reactive hyperemia-peripheral arterial tonometry for that of microvasculature in 88 consecutive patients with chronic heart failure. In 55 patients with ischemic heart disease as an underlying cause of heart failure, flow-mediated vasodilation value was comparable between the two groups of HFrEF (left ventricular ejection fraction < 50%, n = 31) and HFpEF (left ventricular ejection fraction ≥ 50%, n = 24). Reactive hyperemia index measured by reactive hyperemia peripheral arterial tonometry, however, was lower in HFrEF patients compared to HFpEF patients (P = 0.014). In contrast, among 33 patients with non-ischemic heart disease, the degree of flow-mediated vasodilation was lower in HFpEF patients (n = 18) compared with HFrEF patients (n = 15) (P = 0.009), while reactive hyperemia index was comparable between the two groups. The clinical and pathophysiological significance of endothelial function in heart failure differs between conduit artery and microvasculature, and these differences may contribute to the underlying pathophysiology of HFpEF and HFrEF, as well as in ischemic heart disease and non-ischemic heart disease.

ENDOTHELIAL DYSFUNCTION AND CAROTID ARTERY ATHEROSCLEROTIC PHENOTYPES

Endothelial dysfunction plays a key role in the initial development of atherosclerosis. The presence of atherosclerosis by ultrasound examination of the carotid arteries is associated with an increased risk of development of coronary heart disease (CHD) by 1.2% –3.3% per year. The study of the relationship between morphological and functional vascular alterations is an important step toward an improvement of prognostic assessment of the risk of cardiovascular diseases (CVD) and the development of new tools for their prevention. We aimed to perform a systematic review of published studies evaluating the relationship between flow-mediated vasodilation (FMD) during reactive hyperemia test and carotid artery intima-media thickness (IMT). Material and methods. Publications on selected topic were analyzed from 2000 to 2019. We used various Internet resources such as PubMed (https://www.ncbi.nlm.nih.gov/pubmed), Google Scholar (https://scholar.google.ru), the scientific electronic library eLIBRARY.ru (https://elibrary.ru) and major Russian cardiology journals. Results. The analysis of the literature showed that a relationship between a decrease of FMD and an increase of IMT is consistently found in patients with type 2 diabetes mellitus, with verified atherosclerosis of different locations (including CHD and peripheral arterial atherosclerosis), and arterial hypertension. However, these studies were conducted predominantly on small clinical groups (from 10 to 136 people). Few large studies (more than 1000 people) among subjects with arterial hypertension and type 2 diabetes mellitus did not show any convincing relationship between IMT and FMD. In the current literature there is a lack of large studies on the problem, and the data of existing studies are contradictory. New larger studies on this issue are required in various populations and in a wide age range. Conclusion. The studying of association between phenotypes of vasodilation function and structural changes of the vascular wall (for example, between FMD and IMT) remains topical for prognostic assessments of the risk of developing of cardiovascular diseases.

310 Does Improvement in Endothelial Function affect Erectile Function following Stem Cell Therapy in Men with Cardiomyopathy?

Endothelial dysfunction is an important component in the pathogenesis of cardiovascular disease and erectile dysfunction (ED). Interest in cell-based therapy (CBT) for cardiovascular disease and ED is growing. Early trials have shown CBT to improve cardiac function in men with ischemic cardiomyopathy, with concurrent improvement in endothelial function. Whether or not the improvement in endothelial function from CBT may benefit ED has yet to be explored. To determine if a change in endothelial function affects erectile function in men who received transendocardial injection of stem cells. We performed a post hoc sub-analysis of the TRIDENT trial to examine the relationship between endothelial function and erectile function. The TRIDENT study recruited 30 participants with ischemic cardiomyopathy and reduced ejection fraction (<50%) to receive allogenic bone-marrow derived mesenchymal stem cells (MSC) via transendocardial injection (TESI). Participants were randomized to receive MSCs in doses of 20 or 100 million cells and were followed for 1 year. International Index of Erectile Function (IIEF) questionnaires were administered at baseline and at 3, 6 and 12 months. Endothelial function was assessed at baseline and 3 months post-therapy and consisted of two measures: brachial artery percent Flow Mediated Vasodilation (FMD) and quantification of Endothelial Progenitor Cell-Colony Forming Units (EPC-CFUs). Patients with FMD less than 7% were considered to have endothelial dysfunction (normal = >10%), and higher counts of circulating EPCs indicate a greater capacity for endothelial self-regeneration.

A study of endothelial function by flow-mediated vasodilatation in patients with metabolic syndrome

Background: Metabolic syndrome (MetS) is characterized by clustering of cardiovascular risk factors.Endothelial dysfunction is the key early event in atherogenesis that occurs long before structural atherosclerotic changes and promotes cardiovascular events. The assessment of endothelial function by flow-mediated dilation (FMD) of the brachial artery has been proposed as a non-invasive marker for cardiovascular risk. Aim: Assessment of flow mediated vasodilatation of brachial artery as a non invasive marker of endothelial function in metabolic syndrome and To assess the relationship of number of risk factors in metabolic syndrome with endothelial dysfunction. Methodology: A case control study in which 50 patients with Metabolic Syndrome as per new IDF criteria and 50 controls were studied. Detailed clinical history, examination and Blood investigations like Fasting blood glucose, fasting lipid profile and ECG was done for every patients. Endothelial function was assessed by brachial artery flow mediated vasodilatation. Results: In the present study 100 (50 cases and 50 controls) patients were studied, males (54%) and females (46%), majority in the age group between 40-60 years (mean age - 49.76 ± 13.76yrs in cases and 44.94 ± 16.09 years among controls). We identified a significant difference between cases and age- and sex-matched controls regarding brachial artery FMD% (7.24 ± 5.24 and 21.29 ± 9.29 respectively; P value-0.000). Negative corelations were found between FMD% and various variables and also between number of components and FMD% (r = -0.239). Conclusion: MetS is associated with endothelial dysfunction as evidenced by decreased FMD% compared to controls. There is a negative correlation between various components of MetS, number of components of MetS and FMD%.

Relationship between Flow-mediated Endothelial Vasodilation and the Pulse Wave Velocity, and Cervical Carotid Artery Stenosis.

Carotid artery stenosis is elicited by atherosclerosis and is the main cause of cerebral thrombosis. Flow-mediated endothelial vasodilation (FMD) can be measured noninvasively to assess vascular endothelial function related to atherosclerosis. The pulse wave velocity (PWV) is used to evaluate the vascular media involved in atherosclerosis. We investigated the relationship between these measurements in 75 consecutive patients with atherosclerotic cerebral thrombosis. They were assigned to three equal groups based on the severity of carotid artery stenosis on ultrasonograms. Group 1 had no stenosis, group 2 manifested moderate stenosis (<60%), and group 3 presented with severe stenosis (≥60%). We compared the FMD and PWV among the three groups. The PWV was significantly lower in group 1 than the other two groups. The FMD was significantly lower in group 3; it was significantly lower in group 2 than group 1. There was an inverse correlation between the FMD and the severity of carotid artery stenosis. Our findings show that for assessing the severity of carotid artery stenosis, the FMD is more useful than the PWV.

Evaluation of radial artery endothelial functions in transradial coronary angiography according to different radial access sites.

Radial endothelial dysfunction may occur after transradial coronary angiography (CAG). This study aimed to make a comparative evaluation of the radial endothelial functions before and after catheterization between three different radial access sites: left radial (LR) artery, left distal radial (LDR) artery, and right radial (RR) artery. Seventy patients scheduled for elective transradial CAG and intervention from September 6, 2017 to March 6, 2018 were consecutively enrolled. Radial artery endothelial functions of the catheterization arm were measured by flow-mediated vasodilation (FMD) upon admission, at 24 hours, and 2 months following the procedure. LR access was used in 17 patients, whereas the LDR and the RR access were used in 27 and 26 patients, respectively. Basal radial diameters and FMD median values measured on the intervention arm were found to be similar between groups (LR 3.04±0.29 mm, 13.33%; LDR 2.79±0.31 mm; 13.64%; RR 2.74±0.29 mm; 12.52%, p=0.952). The radial vasodilation percentage change expressed as median decreased in all groups 24 hours after the procedure; however, the one with the LDR access was found to be significantly higher than with the LR (9.7% vs. 6.25% p=0.013) and the RR access (9.7% vs. 3.39 p<0.001). A partial recovery of endothelial functions was seen at 2 months after the procedure, approximating to basal values (11.11%; 12%; 10.62%, p=0.079, respectively). Radial artery functions deteriorate early after transradial catheterization. The LDR access seems safer than the other conventional radial access sites in terms of preservation of radial endothelial functions.

Effect on MicroRNA-92a in Atherosclerosis along with FlowMediated Vasodilation Study

Atherosclerosis has been regarded as an inflammatory disease. The vascular endothelium is considered as having multiple functions, regulating vascular tone, thrombosis, haematosis, permeability and cell adhesion. The emergence of microRNAs (miRNAs) as significant regulators of pathophysiological processes has indicated novel molecular insights and provided new therapeutic targets in atherosclerotic condition. Many studies have revealed that miRNA are associated with cardiovascular disease (CVD). With respect to miR-92a, miR -92a, a member of the miR-17 to miR-92 cluster, is expressed highly in endothelial cells (ECs) and regulated by shear stress. Both In vitro and vivo, miR-92a expression is highly induced in atheroprone regions compared with atheroresistant regions under disturbed flow (d-flow) condition. The clinical and experimental studies have suggested that inhibition of miR-92a can contribute to the improvement of endothelial dysfunction, inflammation, and oxidative stress in atherosclerosis. Recent reports showed that antimiR-92a as novel therapeutic options can be attributed to the endothelial cell autophagy and cardiomyocyte metabolism and that mechanistically, atherosclerotic status promote the packaging of functional miR-92a-3p into endothelial microvesicles, thereby promoting angiogenic response into recipient endothelial cells. It is strongly suggested that miR-92a-3p, having novel biological function and mechanism is a potent therapeutic target in atherosclerosis-related diseases. It is putative that flow-mediated vasodilation (FMD) study, early surrogate marker of endothelial function may in part reflect miR-92a, multifunctional biomarker

A prospective, longitudinal monocentric study on laser Doppler imaging of microcirculation: comparison with macrovascular pathophysiology and effect of adalimumab treatment in early rheumatoid arthritis

Increased cardiovascular (CV) morbidity and mortality have been found in rheumatoid arthritis (RA). Tumour necrosis factor α (TNF-α) inhibitors may improve vascular function. In the first part of this study, we determined microcirculation during postoocclusive reactive hyperemia (PORH) representing endothelial function. In a nonselected population (n = 46) we measured flow-mediated vasodilation (FMD) of the brachial artery and laser Doppler flow (LDF) by ultrasound. Among LDF parameters, we determined TH1 (time to half before hyperemia), TH2 (time to half after hyperemia), Tmax (time to maximum) and total hyperemic area (AH). We measured von Willebrand antigen (vWF:Ag) by ELISA. In the second part of the study, we assessed the effects of adalimumab treatment on microcirculatory parameters in 8 early RA patients at 0, 2, 4, 8 and 12 weeks. We found significant positive correlations between FMD and LDF Tmax (R = 0.456, p = 0.002), FMD and TH2 (R = 0.435, p = 0.004), and negative correlation between vWF:Ag and Tmax (R = − 0.4, p = 0.009) and between vWF:Ag and TH2 (R = − 0.446, p = 0.003). Upon adalimumab therapy in early RA, TH2 times improved in comparison to baseline (TH2baseline = 26.9 s vs. TH24weeks = 34.7 s, p = 0,032), and this effect prolonged until the end of treatment (TH28weeks = 40.5, p = 0.026; TH212weeks = 32.1, p = 0.013). After 8 weeks of treatment, significant improvement was found in AHa (AHbaseline = 1599 Perfusion Units [PU] vs. AH8weeks = 2724 PU, p = 0.045). The PORH test carried out with LDF is a sensitive option to measure endothelial dysfunction. TH1 and TH2 may be acceptable and reproducible markers. In our pilot study, treatment with adalimumab exerted favorable effects on disease activity, endothelial dysfunction and microcirculation in early RA patients.

Effects of 1-year anti-TNF-\u03b1 therapy on vascular function in rheumatoid arthritis and ankylosing spondylitis

Accelerated atherosclerosis, increased cardiovascular morbidity and mortality have been associated with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Vascular function, clinical and laboratory markers and the effects of anti-TNF therapy were assessed in arthritides. Fifty-three 53 patients including 36 RA patients treated with either etanercept (ETN) or certolizumab pegol and 17 AS patients treated with ETN were included in a 12-month follow-up study. Ultrasonography was performed to determine flow-mediated vasodilation (FMD), common carotid intima-media thickness (ccIMT) and arterial pulse-wave velocity (PWV) in all patients. All assessments were performed at baseline and 6 and 12 months after treatment initiation. A significant improvement of brachial artery FMD was observed after 6 months (p = 0.004). A tendency of FMD improvement was also observed after 12 months (p = 0.065). ccIMT did not change throughout the year. PWV significantly improved after 12 months (p = 0.034). Higher baseline ccIMT (p = 0.009) and PWV (p = 0.038) were associated with clinical non-response (cNR) versus response (cR) to biologics. Multiple analysis confirmed the association of baseline ccIMT with age (p = 0.003) and cNR (p = 0.009), as well as that of baseline PWV with age at diagnosis (p = 0.022) and current chest pain (p = 0.004). Treatment itself determined the 12-month changes in FMD (p = 0.020) and PWV (p = 0.007). In a mixed cohort of RA and AS patients, TNF inhibition improved or stabilized vascular pathophysiology. Inflammation may be associated with FMD, while, among others, cNR may influence vascular function.

血管内皮機能検査Flow-mediated Vasodilation（FMD）の基準値についての検討

血管内皮機能検査Flow-mediated Vasodilation（FMD）の基準値についての検討

Compromised endothelial function in transgender men taking testosterone

Transgender men (TGM) are persons assigned female gender at birth with a male gender identity and are routinely treated with testosterone. Androgen excess is associated with endothelial dysfunction among cisgender females (CGF) and is an early sign of atherosclerosis and hypertension. To determine the effect of testosterone treatment on endothelial function in TGM. The John B. Pierce Laboratory and Yale School of Medicine. Eleven TGM (age 27±5years; BMI 24.4±3.7kg/m2 ) receiving testosterone (T) and 20 CGF (28±5years; BMI 26.0±5.1kg/m2 ) during the early follicular phase of their menstrual cycle. We evaluated brachial vasodilatory responses following stimuli designed to elicit shear stress using 5-minute occlusion to determine endothelial function (flow-mediated vasodilation, FMD). Total T was greater in the TGM compared to CGF (484.6±122.5 vs 1.5±0.7ng/dL), as was free T (83.9±32.4 vs 1.9±0.8pg/dL). FMD was markedly lower in the TGM (4.5±2.7%) compared to the CGF (8.1±2.9%, P=.002) indicating significantly diminished endothelial function in TGM. We have shown for the first time that in TGM the androgen-dominant hormonal milieu was associated with impaired endothelial function. Endothelial dysfunction precedes clinically detectable atherosclerotic plaque in the coronary arteries, so is an important marker for clinical cardiovascular risk. Therefore, attention to cardiovascular risk factors should be integral to the care of transgender men.

Association between Radiation Exposure and Endothelium-Dependent Vasodilation: Results from Clinical and Experimental Studies.

The association between occupational radiation exposure and endothelium-dependent vasodilation (EDV) remains unclear. This study evaluated the association between radiation exposure and EDV among fluoroscopy-guided interventional procedure specialists and explored the possible mechanisms. Brachial flow-mediated dilation was compared in 21 interventional cardiologists (the radiation group) and 15 noninterventional cardiologists (the nonradiation group). Animal radiation experiments were also performed to observe the impact of radiation on EDV. Flow-mediated dilation in both the left (radiation group, 3.63% vs. nonradiation group, 6.77%; P < .001) and right brachial arteries (5.36% vs. 7.33%, respectively; P= .04) and serum nitric oxide (NO) level (343.69 vs. 427.09 μmol/L, respectively; P= .02) were significantly reduced in the radiation group compared to those in the nonradiation group. EDV was significantly impaired in acetylcholine concentrations of 3× 10-6 mol/L and 10-5 mol/L (60.09% vs.74.79%, respectively; P= .03; and 62.73% vs. 80.56%, respectively; P=.002), and reactive oxygen species levels in the aorta intima and media layers were significantly increased in mice after a single x-ray exposure, which could be partly rescued by pretreatment with folic acid (P < .05). Radiation exposure can lead to impairment of flow-mediated vasodilation in human or EDV in mice. In mice acutely exposed to radiation, folic acid alleviated radiation-induced EDV impairment by possible reduction of reactive oxidative species.

Treating periodontal disease in patients with myocardial infarction: A randomized clinical trial

BackgroundPeriodontitis has been associated with coronary artery disease, but the impact of a periodontal treatment on the endothelial function of patients with a recent ST-segment elevation myocardial infarction (STEMI) was not investigated. MethodsRandomized controlled trial (NCT02543502). Patients admitted between August 2012 and January 2015 were included. Patients were screened during the index hospitalization for STEMI, and those with severe periodontal disease were randomized 2 weeks later to periodontal treatment or to control. The primary endpoint of this trial was the between group difference in the variation of flow-mediated vasodilation (FMD) in the brachial artery assessed by ultrasound from baseline to the 6-month follow-up. Secondary outcomes were cardiovascular events, adverse effects of periodontal treatment and inflammatory markers. ResultsBaseline characteristics were balanced between patients in the intervention (n = 24) and control groups (n = 24). There was a significant FMD improvement in the intervention group (3.05%; p = .01), but not in the control group (−0.29%; p = .79) (p = .03 for the intergroup comparison). Periodontal treatment was not associated with any adverse events and the inflammatory profile and cardiovascular events were not significantly different between both groups. ConclusionsTreatment of periodontal disease improves the endothelial function of patients with a recent myocardial infarction, without adverse clinical events. Larger trials are needed to assess the benefit of periodontal treatment on clinical outcomes. Clinical trial registrationNCT02543502 (https://clinicaltrials.gov/ct2/show/NCT02543502?term=NCT02543502&rank=1).

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.

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. 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 10g of refined cold-pressed flaxseed oil, providing 4.7g ALA (n=29), or 10g of high-oleic sunflower (control) oil (n=30) for 12 weeks. 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 58μmol/L (P=0.02) and 0.14pg/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. 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.

Impaired Endothelial Function in Embolic Stroke of Undetermined Source

BackgroundImpairment of endothelial function is associated with atherosclerosis and atrial fibrillation, and could underlie several types of ischemic stroke. Embolic stroke of undetermined source (ESUS) recently attracted much attention as the major cause of cryptogenic stroke. This study aimed to clarify the endothelial function of patients with ESUS. Methods and ResultsBetween 2015 September and July 2017 July, we used flow-mediated vasodilation (FMD) test to evaluate vascular endothelial function in 182 patients with any vascular risk factors or a history of cerebrovascular events. The subject group was classified into the No Stroke group and 5 stroke subtype groups, large artery atherosclerosis (LAA), cardiogenic embolism (CE), small vessel disease (SVD), ESUS, and others (Other). Endothelial function was expressed as percentage increase in brachial vessel diameter (%FMD) after the interruption of blood flow with mechanical compression for 5 minutes. Mean FMD in the No stroke, LAA, CE, SVD, ESUS and Other groups were 7.03 ± 2.14%, 5.02 ± 2.75%, 4.97 ± 1.62%, 5.19 ± 2.67%, 3.55 ± 1.42%, and 6.55 ± 3.50%, respectively. After the adjustment for confounding factors, FMD was significantly lower in the ESUS group than in the No stroke, SVD, and Other groups. FMD tended to be lower in the ESUS group than in the LAA and CE groups, but the difference was not significant. ConclusionsEndothelial function was impaired in patients with ESUS and may underlie its pathophysiology.

Arginine therapy in mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes.

Purpose of reviewWe would like to inform clinicians that the systematic administration of oral and intravenous l-arginine is therapeutically beneficial and clinically useful for patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), when they maintain plasma arginine concentration at least 168 μmol/l.Recent findingsMELAS is associated with endothelial dysfunction by decreased plasma l-arginine, nitric oxide (NO), and cyclic guanosine monophosphate. Endothelial dysfunction is also evident using flow-mediated vasodilation measurement by high-resolution Doppler echocardiography in the forearm artery in patients with MELAS. l-arginine is known to be an important precursor of NO to normalize the endothelial function in MELAS. In our clinical trial followed by 7 years follow-up study, the systematic administration of l-arginine to patients with MELAS significantly improved the survival curve of patients compared with natural history. Maintaining plasma arginine concentration at least 168 μmol/l may prevent the ictuses through the putative pathophysiologic mechanism and optimal normalization of endothelial dysfunction.SummaryNeither death nor bedriddenness occurred during the 2-year clinical trials, and the latter did not develop during the 7-year follow-up despite the progressively neurodegenerative and eventually life-threatening nature of MELAS. Therapeutic regimen of l-arginine on MELAS may be beneficial and clinically useful for patient care with MELAS.