Measurement Of Flow-mediated Vasodilation Research Articles

New device for assessment of endothelial function: plethysmographic flow-mediated vasodilation (pFMD)

Measurement of flow-mediated vasodilation (FMD) in the brachial artery by using ultrasound is a well-established technique for evaluating endothelial function. To make the measurement quicker and simpler than the measurements of conventional ultrasound FMD (uFMD), we have developed a new noninvasive method, plethysmographic FMD (pFMD), to assess vascular response to reactive hyperemia in the brachial artery. The aim of this study was to determine the accuracy of measurement of pFMD in comparison to that of measurement of conventional uFMD. This study was a multi-center, cross-sectional study. We compared pFMD by a new device using cuff pressure and volume with conventional uFMD using ultrasound in 50 men (mean age, 41 ± 9 years). pFMD significantly correlated with conventional uFMD (β = 0.59, P < 0.001). In Bland–Altman plot analysis of pFMD and conventional uFMD, the mean difference of pFMD and conventional uFMD was 0.78%, and limits of agreement (mean difference ±2 standard deviations of the difference) ranged from −4.53% to 6.11%. We demonstrated validity of the new method for measurement of pFMD, which can automate the evaluation of endothelial function in a short time. Measurement of pFMD is simpler than measurement of conventional uFMD and may have reduced artificial bias compared to that of conventional uFMD measurement (URL for Clinical Trial: https://ethics.hiroshima-u.ac.jp/site/wp-content/uploads/2022/12/eki_giji20221213.pdf. Registration Number for Clinical Trial: E2022-0131).

Seasonal variations in endothelium-dependent flow-mediated vasodilation and endothelium-independent nitroglycerine-induced vasodilation.

Cardiovascular mortality has been shown to vary seasonally. However, it has not been determined whether vascular function is affected by the season. The purpose of this study was to investigate the associations of vascular function with season and outdoor temperature. Between April 2007 and March 2022, measurements of flow-mediated vasodilation (FMD) of the brachial artery as an index of endothelial function and nitroglycerine-induced vasodilation (NID) as an index of endothelium-independent vasodilation were performed in 2190 subjects. There was no significant seasonal difference in FMD (spring, 3.9 ± 3.1%; summer, 3.5 ± 3.0%; fall, 3.7 ± 3.0%; winter, 3.6 ± 3.2%; P = 0.14). There was no significant correlation between FMD and daily mean outdoor temperature (r = -0.02, P = 0.25). Multivariate analyses revealed that neither season (β = -0.020, P = 0.31) nor outdoor temperature (β = 0.005, P = 0.81) was significantly associated with FMD after adjustment for other confounding factors. There were significant seasonal differences in NID (spring, 12.8 ± 6.3%; summer, 12.0 ± 6.1%; fall, 11.7 ± 6.1%; winter, 12.3 ± 5.9%; P = 0.02). However, multivariate analysis revealed that there was no significant association between season and NID after adjustment for other confounding factors (β = -0.012, P = 0.56). There was no significant correlation between NID and daily outdoor mean temperature (r = -0.03, P = 0.17). Multivariate analysis revealed that outdoor temperature was not significantly associated with NID (β = -0.006, P = 0.78). There was no significant association of FMD or NID with season or outdoor temperature, suggesting that it is not necessary to take into account the effects of season and outdoor temperature on vascular function when interpreting the results of FMD and NID measurements. Public trials registry number: UMIN000039512.

The Effects of Exercise Training on Exercise Capacity and Vascular Function after Transcatheter Aortic Valve Implantation-A Pilot Study.

Transcatheter aortic valve implantation (TAVI) improves event-free survival in patients with severe aortic stenosis, but patients' exercise capacity remains poor after the procedure. Therefore, we sought to compare the effects of a supervised center-based exercise training program and unsupervised exercise routine on exercise capacity and vascular function in patients after TAVI. Patients were randomized to either center-based exercise training (12-24 sessions of combined aerobic and low-weight resistance training twice weekly for 8-12 weeks) or an unsupervised home-based exercise routine (initial appraisal with detailed recommendations and monthly follow-up). Exercise capacity (cardiopulmonary testing) and vascular function (ultrasonographic measurement of flow-mediated vasodilation (FMD) and arterial stiffness) were assessed at the baseline and after the study period. We included 23 patients (mean age of 81 years, 61% women), with higher-than-expected drop-out rates (41%) because of the coronavirus-19 pandemic outbreak. Exercise capacity improved over time, irrespective of the intervention group: 0.09 mL/min/kg increase in peak oxygen uptake (95% CI [0.01-0.16]; p = 0.02), 8.2 Watts increase in workload (95% CI [0.6-15.8]; p = 0.034), and 47 s increase in cumulative exercise time (95% CI [5.0-89.6]; p = 0.029). A between-group difference in change over time (treatment effect) was detected only for FMD (4.49%; 95% CI [2.35; 6.63], p < 0.001), but not for other outcome variables. Both supervised and unsupervised exercise training improve exercise capacity and vascular function in patients after TAVI, with supervised exercise training possibly yielding larger improvements in vascular function, as determined by FMD.

The Association of Remnant Cholesterol with Endothelial Dysfunction and Subclinical Atherosclerosis in a Check-Up Population in China.

Vascular endothelial function and atherosclerosis are known to be important risk factors for cardiovascular disease. However, it remains unknown whether remnant cholesterol (RC) correlates with vascular endothelial function and atherosclerosis as represented by flow-mediated vasodilation (FMD) and brachial-ankle pulse wave velocity (baPWV). Therefore, in this study, we aimed to investigate this in the general population. In this study, we examined 13,237 subjects who have undergone blood lipid, FMD, and baPWV measurements. Participants were divided into four groups based on RC quartiles. Multivariable linear regression models were used to calculate odds ratios for FMD and baPWV according to the RC levels. A significant negative relationship was found between RC and FMD (β=-0.14, p=0.014), whereas RC was positively associated with baPWV (β=21.42, p＜0.001), especially in the male and without chronic disease medication populations. The population was divided into three groups according to their lipids: dyslipidemia group, nondyslipidemia but RC increased group (RC ＞0.78 mmol/L), and nondyslipidemia and RC normal group (RC ≤ 0.78 mmol/L). The FMD of the three groups was 7.09%±3.36%, 7.39%±3.38%, and 7.57%±3.54%, respectively. The baPWV of the three groups was 1445.26±261.56 cm/s, 1425.04±265.24 cm/s, and 1382.73±267.75 cm/s. Significant differences were noted between the groups. The findings indicated that a higher RC was an independent predictive factor for participants with endothelial function and atherosclerosis. It is important to use RC as a risk management indicator of vascular function, especially for those with normal conventional lipid parameters but increased RC.

S-11-5: CLINICAL IMPLICATION OF FMD

A healthy endothelium maintains vascular tone and structure by regulating the balance between vasodilation and vasoconstriction, growth inhibition and growth promotion, antithrombosis and prothrombosis, anti-inflammation and proinflammation, and also antioxidation and pro-oxidation. The vascular endothelium is involved in the release of various vasodilators, including nitric oxide (NO), prostaglandins, and endothelium-derived hyperpolarizing factor as well as vasoconstrictors. NO plays an important role in the regulation of vascular tone, the inhibition of platelet aggregation, and the suppression of smooth muscle cell proliferation. Cardiovascular diseases are associated with endothelial dysfunction. In addition, endothelial dysfunction is an early feature of atherosclerosis and vascular diseases in humans. Therefore, it is clinically important to estimate the degree of endothelial dysfunction. Several methods have been used to assess endothelial function in humans. Measurement of flow-mediated vasodilation (FMD) using an ultrasound is noninvasive and is an accurate indicator of NO production. Measurement of FMD is widely performed as an index of conduit artery endothelial function. Several investigators have shown that FMD is an independent predictor for cardiovascular outcomes. It is thought that FMD is useful for surrogate endpoint of cardiovascular outcomes and index of atherosclerotic treatment. However, the evaluation technique by the FMD measurement system still requires skills in measurement of the vessel diameter by an ultrasound system, and is difficult to handle. In addition, there is a problem in that the technique requires a large-scale apparatus and lacks in simplicity. In this session, we would like to explain in detail concerning the methods of assessing and clinical importance of endothelial function, especially FMD.

Study of Endothelial Dysfunction in Patients With Non-alcoholic Fatty Liver Disease.

BackgroundMetabolic syndrome (syndrome X) is the name for a group of risk factors that raises your risk for heart disease and other health problems, such as diabetes and stroke. Dilatation of blood vessels following stress is a function of vasodilators produced by the endothelium. Flow-mediated vasodilation assesses endothelial function. In the case of endothelial dysfunction, flow-mediated vasodilation is impaired, resulting in decreased or even absence of vasodilation following stress. The easy availability of ultrasound machines nowadays and the non-invasive nature of the test make this a practical test for assessing endothelial dysfunction and the risk of cardiovascular diseases. Various studies have confirmed the presence of impaired flow-mediated vasodilation in patients with coronary artery disease. However, the presence of impaired flow-mediated vasodilation in individuals with risk factors but no cardiovascular diseases can prove that this can be used to predict individuals at risk. This study tries to confirm the presence of endothelial dysfunction in patients with non-alcoholic fatty liver disease (NAFLD) attending a tertiary center hospital in Kochi.ObjectivesThe study's main aim is to compare flow-mediated dilatation in patients with NAFLD and normal individuals.Materials and methodsThe comparative study was conducted among 50 patients attending various outpatient departments in Amrita Institute of Medical Sciences, Kochi. History and examination of cases and controls and relevant investigations were done after obtaining consent. In addition, both groups underwent measurement of flow-mediated vasodilation in the radiology department. Data were entered in Microsoft Excel and were analyzed using SPSS.ResultsFlow-mediated vasodilation was found to be less in patients with fatty liver (7.37 ± 2.75) when compared to individuals with normal liver (12.41 ± 3.71). In addition, flow-mediated vasodilatation was inversely proportional to BMI and age.ConclusionThis study has proved that there will be endothelial dysfunction in NAFLD, as shown by the decrease in flow-mediated vasodilation when compared with normal liver.

Influence of systemic manifestations of inflammatory bowel diseases on endothelial function and cardiovascular risk.

Inflammatory bowel diseases (IBD) may be complicated by extraintestinal manifestations (EIM). Both conditions may be implicated in the overall increase of cardiovascular (CV) risk profile of the patients. The study aimed to assess CV risk in IBD patients with EIMs in relation to the stages of both diseases. A total of 70 (38 men, mean age 51.7±12.4 years) patients with IBD and 22 controls (12 men, mean age 49.2±13.6 years) were enrolled. All patients and controls were screened for extraintestinal manifestations and underwent physical and anthropometric examinations, standard laboratory investigations, ultrasound evaluation of carotid arteries and flow-mediated vasodilatation (FMD). Patients were divided into four groups in relation to their active or remission stage of disease: 1) IBD+ EIM+; 2) IBD+ EIM-; 3) IBD- EIM+; and 4) IBD- EIM-. The groups were homogenous according to their clinical characteristics. Patients with both IBD and EIM in active phase showed significantly lower values in FMD than controls (P=0.024). Carotid intima-media thickness values (cIMT) were similar among groups. Patients with active phases of IBD and/or EIM showed statistically significant lower values in FMD measurements (P=0.0008 and P=0.0011, respectively). Multivariate regression did not reveal any independent predictors for FMD values. The active phase of IBD or EIM or both may promote endothelial dysfunction in patients, thus increasing their CV risk profile. Patients in remission phase showed endothelial function similar at controls.

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.

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.

FLOW MEDIATED VASODILATION/VASOCONSTRICTION IN DIFFERENT DISEASE POPULATIONS

Objective: Flow-mediated vasodilation (FMD) has become one of the most widely assessed parameter to analyze endothelial function. However, some techniques used to measure FMD have limitations. Recently, finger plethysmography (EndoPAT) failed to show any kind of reproducibility. A semi-automatic device called UNEX has been developed, which overcomes the limitation of classic systems (in particular the investigator-dependency of conventional, “hand-held” FMD measurements). We report about our first experience by using this device.Design and method: UNEX is a semi-automatic ultrasound system using an H-type ultrasound probe. This system comprised a 7.5-MHz linear array transducer and a novel stereotactic probe-holding device (UNEX EF 18G; UNEX Co., Nagoya, Japan). Another advantage of this device is the continuous recording of B-mode images and A-mode waves of the artery in the longitudinal plane, so that continuous measurement of arterial diameter in the 4.5 min following cuff deflation occurs. Finally, this semi-automatic assessment of FMD has been shown to improve the precision and repeatability of the measurement. FMD and flow mediated vasoconstriction (L-FMC) were measured in patients with heart failure, patients with estimated glomerular filtration rate less and more than 60 ml/min/1,73m2 and healthy subjects using UNEX system. Results: 67% of patients without nephropathy were patients with type 2 diabetes and 33% with hypertension. 22% of patients with nephropathy were on dialysis and 78% had an eGFR less than 60 ml/min/1,73m. Compared to other disease population patients with heart failure were older and healthy population was younger. Conclusions: Our data reveal FMD- and L-FMC values in 3 different disease populations. Updated values on FMD and L-FMC and more detailed analysis will be presented at the meeting.

Effects of different doses of ticagrelor on platelet aggregation and endothelial function in diabetic patients with stable coronary artery disease

We performed this study to observe the effects of different doses of ticagrelor and standard-dose clopidogrel on platelet reactivity and endothelial function in diabetic patients with stable coronary artery disease (CAD). Sixty type 2 diabetic patients were assigned to one-quarter standard-dose ticagrelor, half standard-dose ticagrelor, standard-dose ticagrelor and standard-dose clopidogrel groups. Light transmission aggregometry (LTA) and VerifyNow assay were used to measure platelet function. Endothelial function was assessed by measurement of flow-mediated vasodilation (FMD) and plasma von Willebrand factor (VWF) levels were detected. Enzyme-linked immunosorbent assay (ELISA) examined the Interleukin-8(IL-8) and IL-10. The results suggested that the one-quarter dose (34.0%± 14.7%), half-dose (26.9%± 11.6%) and standard-dose (17.3%± 10.3%) ticagrelor showed lower platelet aggregation rate than clopidogrel (52.8%± 18.3%; P ＜0.0001). PRU values in three ticagrelor groups were lower than that in clopidogrel group (102 (76–184)；75 (33–88)；38 (11–52) versus 194 (138–271) and；P ＜0.0001). FMD levels were higher in ticagrelor groups compared with baseline levels while lower in clopidogrel group after treatment. However, no significant differences were found in the percentage increase in the FMD between ticagrelor groups and clopidogrel group. The levels of VWF after treatment were lower than the baseline levels, but there was no statistically significant difference between ticagrelor group and clopidogrel group after treatment. The concentration of IL-8 and IL-10 were decreased in patients with half and standard-dose ticagrelor group. In conclusion, one-quarter standard-dose ticagrelor produced similar inhibitory effects on platelet aggregation as standard-dose clopidogrel in diabetic patients with stable CAD. The half standard-dose ticagrelor had a similar inhibitory effect on platelet inhibition as standard-dose ticagrelor, which was stronger than that of clopidogrel. Moreover, the half-dose ticagrelor had equal protection of endothelial function and inhibition of inflammatory factor as standard-dose ticagrelor.

New assessment of endothelial function measured by short time flow-mediated vasodilation: Comparison with conventional flow-mediated vasodilation measurement

BackgroundMeasurement of flow-mediated vasodilation (FMD) is an established method for assessing endothelial function. Measurement of FMD is useful for showing the relationship between atherosclerosis and endothelial function, mechanisms of endothelial dysfunction, and clinical implications including effects of interventions and cardiovascular events. To shorten and simplify the measurement of FMD, we have developed a novel technique named short time FMD (stFMD). We investigated the validity of stFMD for assessment of endothelial function compared with conventional FMD. Methods and resultsWe evaluated stFMD and conventional FMD in 82 subjects including patients with atherosclerotic risk factors and cardiovascular disease (66 men and 16 women, 57 ± 16 years). Both stFMD and conventional FMD were significantly correlated with age, systolic blood pressure, diastolic blood pressure and baseline brachial artery diameter. In addition, stFMD was significantly correlated with conventional FMD (r = 0.76, P < 0.001). Bland-Altman plot analysis showed good agreement b etween stFMD and conventional FMD. Moreover, stFMD in the at risk group and that in the cardiovascular disease group were significantly lower than that in the no risk group (4.6 ± 2.3% and 4.4 ± 2.2% vs. 7.3 ± 1.9%, P < 0.001, respectively). Optimal cutoff value of stFMD for diagnosing atherosclerosis was 7.0% (sensitivity of 71.0% and specificity of 85.0%). ConclusionsThese findings suggest that measurement of stFMD, a novel and simple method, is useful for assessing endothelial function. Measurement of stFMD may be suitable for screening of atherosclerosis when repeated measurements of vascular function are required and when performing a clinical trial using a large population. Clinical trial registration informationURL for Clinical Trial: http://UMIN; Registration Number for Clinical Trial: UMIN000025458.

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

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. 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. 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). 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).

Abstract P505: Longitudinal Associations Among Flow-mediated Vasodilatation, Preclinical Vascular/renal Damage and Serum Cholesterol Levels in Treated Hypertension

Objective: The endothelial dysfunction is thought to be an early precursor of vascular/renal damages. The present study was conducted to examine whether endothelial dysfunction, as assessed by measurement of flow-mediated vasodilatation (FMD), is longitudinally associated with the progression of vascular/renal damage, and also to identify factors that can perpetuate endothelial dysfunction in treated hypertension. Methods and Results: A 3-year multicenter prospective observational study was conducted in 674 Japanese patients with hypertension receiving antihypertensive medication, in whom the carotid intima-media thickness/plaque (CIMT), brachial-ankle pulse wave velocity (baPWV), estimated glomerular filtration rate (eGFR), urinary albumin/creatinine excretion ratio (UACR) and FMD were measured thrice at 1.5-year intervals. A lower value of the FMD at the study baseline was associated with a higher rate of increase of the baPWV during the study period (The change of baPWV during the study period was -25 cm/sec in subjects with the highest quartile range of FMD vs. +18 cm/sec in subjects with the lowest quartile range of FMD, p&lt;0.05). However, no association of the FMD at the study baseline was observed with any of the other markers of vascular/renal damage examined. Mixed model linear regression analysis revealed a significant inverse relationship of the FMD at each measurement point with the baPWV at each measurement point (beta estimate = -10.97, P &lt; 0.01); furthermore, the serum level of low density lipoprotein cholesterol (LDLC) at the study baseline was also inversely associated with the longitudinal changes of the FMD values (estimate = -0.39, P &lt; 0.01). Conclusion: Our results suggest that an “endothelial dysfunction-arterial stiffening continuum” may exist in treated hypertension, and endothelial dysfunction, as measured by FMD, may be more closely associated with the arterial stiffness than with other parameters of preclinical renal/vascular damage. Furthermore, inadequate control of LDLC may also contribute to the progression of endothelial dysfunction.

Measurement of Flow-Mediated Vasodilatation.

The FMDJ study, a multicenter prospective observational study conducted in Japan, demonstrated the acceptable reliability of measurement of flow-mediated vasodilatation (FMD) using a semi-automatic device in individual institutions. However, in about 10% of Japanese subjects, adequate scans to determine the brachial arterial diameter failed to be obtained. The prevalence of inadequate scans was higher in women than in men, while obesity had no influence on the inadequate scan rate. The FMDJ study also proposed that attending periodic refresher courses on the measurement of FMD is needed for maintaining competency. Finally, the FMDJ study proposed reference values for FMD. Thus, FMD measurement may be categorized as a clinically applicable tool on the basis of class IIb (exploratory cohort study with good reference standards) evidence.

The AGE-RAGE Axis and Its Relationship to Markers of Cardiovascular Disease in Newly Diagnosed Diabetic Patients.

AimThe purpose of the study was the simultaneous measurement of all the different components of the AGE-RAGE axis as well as several non-invasive markers of cardiovascular disease (CVD) in a cohort of newly diagnosed diabetic patients.Materials and MethodsIn 80 newly diagnosed diabetic patients we measured serum carboxymethyllysine (CML), soluble RAGE (sRAGE) and peripheral mononuclear (PMNC) RAGE and AGER1 mRNA together with ICAM-1, VCAM-1, and malondialdehyde (MDA). We also assessed cardiovascular function by measurement of flow-mediated vasodilation (FMD), intima-media thickness (IMT) and arterial stiffness. Univariant correlation analysis was used to determine correlation between the variables in the study and multiple regression analysis was used to examine the association between the AGE-RAGE axis components and FMD, IMT and arterial stiffness.ResultsSerum CML correlated positively with sRAGE, PMNC RAGE, HOMA-IR, ICAM-1, VCAM-1 and MDA, but inversely with PMNC AGER1. sRAGE and RAGE was positively correlated with AGER; IMT was positively correlated with HOMA-IR, ICAM-1, VCAM-1, MDA, and sRAGE and arterial stiffness had correlation with HOMA-IR, ICAM-1, VCAM-1, MDA, CML, sRAGE, AGER1 and RAGE. In multivariate analysis we found a significant relationship between CML with PMNC RAGE, HOMA-IR; sRAGE with VCAM-1 and MDA; PMNC RAGE with PMNC AGER1and CML; PMNC AGER1 with PMNC RAGE; FMD with sRAGE, CML and HbA1c; IMT with sRAGE, and arterial stiffness with sRAGE, sCML and AGER1ConclusionsWe found significant and strong associations between the different components of the AGE-RAGE axis and also found significant association between AGE-RAGE axis markers, especially sRAGE with several noninvasive markers of cardiovascular disease risk. sRAGE, an easily measured parameter in blood, may potentially be used as a surrogate marker of AGEs-RAGE in patients with diabetes.

Relationship between serum triglyceride levels and endothelial function in a large community-based study

Background and aimsIt is established that low-density lipoprotein cholesterol is an independent risk factor for cardiovascular events. Recently, circulating triglycerides level has been focused on as a risk factor for cardiovascular events. In this study, we evaluated the associations between triglycerides and endothelial function in a general population. MethodsWe analyzed data for 4887 subjects who were enrolled in the FMD-Japan registry. We investigated cross-sectional associations between serum triglyceride levels and endothelial function assessed by measurement of flow-mediated vasodilation (FMD). ResultsSerum triglyceride levels were correlated with FMD (r = −0.12, p < 0.001). Subjects were divided into six groups based on serum triglyceride levels. FMD was significantly decreased with an increase in serum triglyceride levels (≤0.71 mmol/L, 7.0 ± 3.5%; 0.72–0.94 mmol/L, 6.3 ± 3.5%; 0.95–1.19 mmol/L, 6.0 ± 3.1%; 1.20–1.48 mmol/L, 5.8 ± 3.2%; 1.49–2.02 mmol/L, 5.7 ± 3.1%; ≥2.03 mmol/L, 5.5 ± 3.0%; p for trend <0.001). After adjustment for age, sex, and cardiovascular risk factors, including high-density lipoprotein cholesterol, serum triglyceride levels of more than 1.20 mmol/L were independently associated with the low quartile of FMD (1.20–1.48 mmol/L, odds ratio (OR) 1.41, 95% confidence interval (CI) 1.09 to 1.82; 1.49–2.02 mmol/L, OR 1.31, 95% CI 1.00 to 1.70; ≥2.03 mmol/L, OR 1.48, 95% CI 1.13 to 1.95) using serum triglyceride levels of less than 0.71 mmol/L group as the reference. ConclusionsThese findings suggest that triglycerides are an independent predictor of endothelial function. Lowering circulating triglyceride levels may improve endothelial function, leading to a decrease in cardiovascular events. Clinical trial registration informationURL for Clinical Trial: http://UMIN; Registration Number for Clinical Trial: UMIN000003409

Association Between Peripheral Vascular Endothelial Function and Progression of Open-Angle Glaucoma.

The aim of the study is to evaluate the relationship between Humphrey visual field progression and peripheral vascular endothelial function in patients with open-angle glaucoma (OAG), assessed by noninvasive endothelium-dependent flow-mediated vasodilation (FMD).Forty OAG patients, among which 22 had normal-tension glaucoma (NTG) and 18 had primary open-angle glaucoma (POAG) were enrolled. Each enrolled patient underwent a thorough ophthalmological examination including the Humphrey visual field test and measurement of FMD via high-resolution 2-dimensional ultrasonographic imaging of the brachial artery. Blood samples were evaluated for biochemistry and lipid profiles as well as levels of high-sensitivity C-reactive protein (hsCRP). The annual change of threshold sensitivity of the visual field in each test location were analyzed with pointwise linear regression. The correlation between long-term visual field progression and FMD was evaluated.A mean follow-up of 7.47 ± 1.84 years revealed a faster progression rate over the superior visual field in all 40 OAG patients (superior field −0.24 ± 0.67 dB/y, inferior field −0.10 ± 0.59 dB/y, P = 0.37). However, only the annual sensitivity change of the inferior peripheral field showed correlation with baseline FMD. There was no significant difference in the change slope of visual field between NTG and POAG patients.A correlation between baseline brachial artery FMD and visual field progression was observed in the inferior peripheral field in patients with NTG and POAG. This result suggests that peripheral vascular endothelial dysfunction may be related to glaucoma progression.

Metformin is not just an antihyperglycaemic drug but also has protective effects on the vascular endothelium.

Metformin, a synthetic dimethyl biguanide, has been in clinical use for over 55years, and today is considered the first-choice drug for the treatment of type 2 diabetes used by an estimated 125million people worldwide. Metformin is orally effective, not metabolized, excreted unchanged by the kidney, relatively free of side effects and well tolerated by the majority of patients. Of importance is that the United Kingdom Prospective Diabetes Study 20-year study of type 2 diabetics, completed in 1998, compared patients treated with insulin, sulfonylureas and metformin and concluded that metformin provided vascular protective actions. Cardiovascular disease is the primary basis for the high morbidity and mortality that is associated with diabetes and that metformin proved to be protective resulted in a dramatic increase in its use. The vascular protective actions of metformin are thought to be secondary to the antihyperglycaemic effects of metformin that are mediated via activation of AMP kinase and subsequent inhibition of hepatic gluconeogenesis, fatty acid oxidation as well as an insulin sensitizing action in striated muscle and adipose tissue. As reflected by a number of clinical studies, patients treated with metformin also have improvement in endothelial function as measured by the use of plethysmography and measurement of flow-mediated vasodilatation. These data as well as data from animal studies are supportive that metformin has a direct protective action on the vascular endothelium. In this review article, we discuss the pharmacology of metformin and critique the literature as to its cellular sites and mechanism(s) of action.

Abstract 10041: Increased Triglyceride Levels are Associated With Endothelial Dysfunction: FMD-Japan Registry

Objective: In contrast to low-density lipoprotein cholesterol, and high density lipoprotein cholesterol, which are well-established independent risk factors for cardiovascular disease, the importance of triglycerides remains controversial. In this study, we evaluated the associations between triglycerides and endothelial function in the general population. Methods and Results: We enrolled 4,908 subjects (3842 men and 1066 women; mean age, 48±12 years) who were enrolled in FMD-Japan registry. And, we investigated cross-sectional associations between triglycerides and endothelial function by measurement of flow-mediated vasodilation (FMD). The triglycerides levels were negatively associated with FMD (r=-0.10, P&lt;0.001). Subjects were divided into six groups on the basis of the triglycerides level. FMD was significantly decreased with an increase in the triglycerides level (≤63 mg/dL, 7.0±3.5%; 64 to 83 mg/dL, 6.3±3.5%; 84 to 105 mg/dL, 6.0±3.1%; 106 to 131 mg/dL, 5.8±3.2%; 132 to 179 mg/dL, 5.7±3.1%; ≥180 mg/dL, 5.5±3.0%; P for trend&lt;0.001). After adjustment for age, sex, cardiovascular risk factors including high density lipoprotein cholesterol, high triglycerides level groups independently remained associated with low quartile of FMD using the triglycerides ≤63 mg/dL group as the reference (Table). Conclusions: These findings supported an independent association between triglycerides and cardiovascular disease.