The evaluation of endothelial functions in patients with celiac disease

Aim: Celiac disease is characterized by malabsorption resulting from inflammatory injury to the mucosa of the small intestine after the ingestion of wheat gluten or related rye and barley proteins. This study aimed to identify individuals who are at risk of heart failure and increased risk for cardiovascular events by evaluating endothelial function in patients with celiac disease. Materials and Methods: The study included 36 patients with celiac disease and 35 healthy volunteers. After all routine laboratory examination, left ventricular functions were evaluated with standard two‐dimensional, M‐mode conventional Doppler methods. Then, flow‐mediated dilatation and nitroglycerin‐dependent dilatation tests on brachial artery were performed to all patients and controls. Results: A total of 36 celiac patients and 35 healthy volunteers were included in the study. The brachial artery diameter at baseline was similar between both groups. Measured brachial artery diameter after hyperemia was 30.19 ± 4.47 mm in celiac patients and 32.35 ± 3.77 mm in the control group. Differences between two groups were statistically significant (P = 0.031). Flow‐mediated vasodilatation was lower in celiac patients compared with in controls (10.61 ± 2.64% vs 13.09 ± 2.9%; P = 0.0003). Measured endothelium‐independent vasodilatation in the brachial artery before and after nitroglycerin was similar between both groups (P = 0.09 and P = 0.07, respectively). Conclusion: This research which aimed to evaluate endothelial dysfunction in patients with celiac disease is the first in the literature. As a result of this study, we found endothelial dysfunction at the macrovascular level in celiac patients. (Echocardiography 2012;29:471‐477)     

The effect of acute hyperglycaemia on brachial artery flow mediated dilatation in normal volunteers

Abstract Background : Endothelial function is known to be abnormal in patients with diabetes and acute hyperglycaemia may play an aetiological role.
Aims : The aim of this randomised controlled study was to determine if acute systemic hyperglycaemia impairs endothelial function in normal subjects.
Methods : Endothelial function was assessed by the change in brachial artery diameter in response to forearm ischaemia using B-mode ultrasound in ten healthy subjects (eight male) aged 19–35 years. Brachial artery blood flow velocity and diameter were measured before and after five minutes of forearm ischaemia. Measurements were performed in the supine position after an overnight fast, before and after 60 minute infusions of 0.9% saline or 10% dextrose. Measurements were made on two separate occasions at least 24 hours apart, and subjects were randomised to saline first or dextrose first. The largest diameter measured after ischaemia was divided by the resting arterial diameter to calculate percent dilatation of the artery from baseline, and is reported as flow-mediated dilatation (FMD).
Results : Dextrose infusion resulted in a significant rise in mean (SD) serum glucose 5.2 (0.1) to 9.2 (0.3) mmol/L and insulin concentration 6.3 (1.4) to 20.6 (3.7) mU/L p <0.002. Brachial artery blood flow velocity and diameter increased significantly from baseline after ischaemia ( p <0.002). Mean FMD (SEM) before and after infusion were not, however, significantly different ( p =0.4) (pre-saline 7.3 [1.0]%, post saline 5.2 [1.5]% and predextrose 8.1 [2.0]%, post dextrose 5.9 [1.7]%).
Conclusions : These data suggest that acute hyperglycaemia does not impair FMD in normal subjects.     

A New Noninvasive Method in Evaluating the Endothelial Function: The Measurement of the Resistive Index after Reactive Hyperemia of the Brachial Artery

Objective: The objective of our study was to investigate whether the measurement of the resistive index (RI) after reactive hyperemia is a relevant method for the evaluation of the endothelial function. Materials and methods: 54 hypertensive patients and 27 controls were prospectively enrolled for the study. In addition to the flow‐mediated dilation (FMD), the RI was also measured during the same procedure. RI is a vascular resistance parameter that is most commonly used to minimize the intra‐ and interobserver variability because of its reliability among repeated measurements. The percent change of the RI after reactive hyperemia (HRI) in comparison to the baseline RI was defined as the flow‐mediated RI (FMRI). (FMRI = 100 ×[HRI ? baseline RI/baseline RI]). Results: The groups were comparable in terms of age, sex, and left ventricular ejection fraction. Differences were present in the systolic arterial pressure (mmHg; 161 ± 15 vs. 114 ± 7, P = 0.000), diastolic arterial pressure (mmHg; 96 ± 7 vs. 72 ± 7, P = 0.000) and left ventricular mass index (g/m^2; 124 ± 5 vs. 99 ± 6, P = 0.002). As expected, the FMD differed significantly between hypertensive and control groups (4 ± 4% vs. 13 ± 12%, respectively; P = 0.000). There was also a significant difference in the FMRI values between the groups (?21 ± 10; ?30 ± 14, P = 0.002). FMD and FMRI values were negatively correlated (P < 0.05). Conclusion: For the noninvasive evaluation of the endothelial function, FMRI value measured as RI value after reactive hyperemia can be a good alternative to the FMD measured as vascular diameter after reactive hyperemia. (Echocardiography 2010;27:873‐877)     

Long‐term effects of weight loss with a very low carbohydrate and low fat diet on vascular function in overweight and obese patients

Abstract. Wycherley TP, Brinkworth GD, Keogh JB, Noakes M, Buckley JD, Clifton PM. (Commonwealth Scientific and Industrial Research Organization, Food and Nutritional Sciences; School of Molecular and Biomedical Science, University of Adelaide; and Nutritional Physiology Research Centre and Australian Technology Network Centre for Metabolic Fitness, Sansom Institute for Health Research, University of South Australia). Long‐term effects of weight loss with a very low carbohydrate and low fat diet on vascular function in overweight and obese patients. J Intern Med 2010; 267 : 452–461. Objective. To compare the effects of an energy reduced very low carbohydrate, high saturated fat diet (LC) and an isocaloric high carbohydrate, low fat diet (LF) on endothelial function after 12 months. Design and Subjects. Forty‐nine overweight or obese patients (age 50.0 ± 1.1 years, BMI 33.7 ± 0.6 kg m^?2) were randomized to either an energy restricted (～6–7 MJ), planned isocaloric LC or LF for 52 weeks. Body weight, endothelium‐derived factors, flow‐mediated dilatation (FMD), adiponectin, augmentation index (AIx) and pulse wave velocity (PWV) were assessed. All data are mean ± SEM. Results. Weight loss was similar in both groups (LC ?14.9 ± 2.1 kg, LF ?11.5 ± 1.5 kg; P = 0.20). There was a significant time × diet effect for FMD (P = 0.045); FMD decreased in LC (5.7 ± 0.7% to 3.7 ± 0.5%) but remained unchanged in LF (5.9 ± 0.5% to 5.5 ± 0.7%). PWV improved in both groups (LC ?1.4 ± 0.6 m s^?1, LF ?1.5 ± 0.6 m s^?1; P = 0.001 for time) with no diet effect (P = 0.80). AIx and VCAM‐1 did not change in either group. Adiponectin, eSelectin, tPA and PAI‐1 improved similarly in both groups (P < 0.01 for time). Conclusion. Both LC and LF hypoenergetic diets achieved similar reductions in body weight and were associated with improvements in PWV and a number of endothelium‐derived factors. However, the LC diet impaired FMD suggesting chronic consumption of a LC diet may have detrimental effects on endothelial function.     

Effects of fluvastatin, an HMG-CoA reductase inhibitor, on serum levels of interleukin-18 and matrix metalloproteinase-9 in patients with hypercholesterolemia

BACKGROUND: Interleukin-18 (IL-18), a novel proinflammatory marker, and matrix metalloproteinase-9 (MMP-9) represent the indices of plaque stability. It is unknown whether hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins), which provide anti-inflammatory and endothelium protection effects, have the property of stabilizing plaque in patients with hypercholesterolemia. HYPOTHESIS: The study was designed to investigate the influence of statin therapy in circulating IL-18, MMP-9, and endothelial function. METHODS: We investigated the effects of a 12-week therapy with fluvastatin on IL-18, MMP-9, and endothelial function in patients with hypercholesterolemia. RESULTS: Compared with placebo, fluvastatin significantly improved flow-mediated vasodilatation to hyperemia, a hallmark of endothelial function [from 3.8% (-3.9 approximately 15.2) to 5.9% (-0.3 approximately 13.2), p = 0.001], and attenuated plasma levels of high sensitivity C-reactive protein (hsCRP) [from 1.3 (0.3 approximately 7.7) to 1.1 mg/l (0.2 approximately 3.5), p = 0.018], IL-18 [from 247.6 (145.4 approximately 378.4) to 196.4 pg/dl (90.7 approximately 380.2), p <0.001], total MMP-9 (from 58 +/- 46.3 to 39.4 +/- 22.4 ng/dl, p = 0.023), and MMP-9 activity [from 6.4 (3.6 approximately 27) to 5.6 ng/dl (3.1 approximately 13.7)]. However, no significant correlation was found between the degree of changes in lipid profile and flow-mediated dilatation (FMD) and plasma concentration of IL-18 and MMP-9. CONCLUSIONS: Fluvastatin reduced plasma concentrations of IL-18 and MMP-9, and improved endothelial function in patients with hypercholesterolemia independent of its lipid-lowering effect.     

Endothelial function and peripheral vasomotion in the brachial artery in neurally mediated syncope

BACKGROUND: Paradoxical peripheral vasodilation is one of the suspected mechanisms of neurally mediated syncope. Parasympathetic stimulation following sympathetic activation during orthostatic stress mainly contributes to this vasodilation. HYPOTHESIS: Since endothelial function modulates peripheral vascular tone, this study aimed to determine whether endothelial function and inappropriate peripheral vasomotion has a significant role in the pathogenesis of neurally mediated syncope. METHODS: To investigate whether endothelial function is augmented or whether abnormal peripheral vasomotion exits, flow-mediated dilation (FMD, endothelium-dependent vasodilation) and sublingual glyceryl trinitrate-induced dilation (0.3 mg, GTN-D, endothelium-independent vasodilation) were measured in the brachial artery in 16 patients with neurally mediated syncope, aged 33 +/- 10 years, by using high-resolution ultrasound. All patients underwent positive head-up tilt testing. These measures were compared with those in 16 control subjects matched with the patients by age, gender, and coronary risk factors. For FMD, percent diameter changes were obtained from baseline to hyperemic conditions (1 min after 5 min occlusion of the forearm artery). There were five smokers in both the patient and the control groups, but there was no structural heart disease in either group. RESULTS: Baseline brachial artery diameters were comparable (3.8 +/- 0.6 vs. 3.8 +/- 0.7 mm, NS). Flow-mediated dilation in patients with neurally mediated syncope had a normal value of 9.8 +/- 5.0% despite the inclusion of five smokers. Flow-mediated dilation and GTN-D in patients with neurally mediated syncope were significantly greater than those in controls (9.0 +/- 5.0 vs. 3.0 +/- 3.5%, p<0.05; 18.4 +/- 5.5 vs. 14.1 +/- 4.4%, p<0.05). CONCLUSIONS: Augmented endothelial function and/or abnormal peripheral vasomotion in peripheral arteries are important in patients with neurally mediated syncope in selected populations.     

Combined examination of glyceryl trinitrate‐mediated vascular dilation with flow‐mediated vascular dilation is essential for assessment of vascular function in type 2 diabetes

Aims/Introduction

In order to characterize the impaired vascular function in type 2 diabetes (DM) patients, we evaluated the flow‐mediated vascular dilation (FMD) with glyceryl trinitrate‐mediated vascular dilation (NMD) using ultrasonography.

Materials and Methods

A total of 111 DM patients and 42 healthy control participants were studied. The maximal dilatation of FMD and NMD (%FMD and %NMD, respectively), the beginning time (T) of dilatation after stimulation and the velocity (V) of the vascular dilatation were also measured.

Results

Among DM patients, 49% had impaired %NMD, which affects the results of %FMD. In DM patients with normal %NMD, the %FMD was also significantly lower than that in control participants, although the T and the V were not impaired. In contrast, both the T and the V were disturbed in the DM patients with low %NMD. Multiple linear regression analysis showed that %NMD was independently correlated with albuminuria. Our results indicate that the impaired FMD in DM is be affected by low NMD, and impaired endothelial function already exists even in DM patients whose vascular smooth muscle function is still retained, and also albuminuria is the clinical feature of DM with low %NMD.

Conclusions

Examination of NMD, not only FMD, should be carried out as it offers the possibility of clarifying vascular function in DM patients.     

肱动脉血流介导的内皮依赖性舒张功能的变化对冠状动脉病变的预测价值

目的探讨肱动脉血流介导的内皮依赖性舒张功能(FMD)变化与冠状动脉病变程度的相关性,为血管内皮功能检测可用于筛查早期冠心病提供临床依据。方法纳入临床疑似冠心病拟行冠状动脉造影(CAG)的患者,共130例。所有患者均于CAG检查前行FMD检查。根据造影结果将患者分为冠心病组和非冠心病组。将冠心病组、非冠心病组进一步分为不同亚组,分析FMD与冠状动脉病变程度的相关性。绘制ROC曲线,寻找FMD诊断冠心病的最佳界值。结果冠心病组收缩压、同型半胱氨酸、糖化血红蛋白均高于非冠心病组(P0.01或P0.05)。冠心病组FMD较非冠心病组明显降低(P0.01)。各亚组间分析显示,正常组FMD分别高于冠状动脉硬化组、单支病变组、双支病变组及三支病变组(P0.05或P0.01),冠状动脉硬化组FMD均高于双支病变组及多支病变组(P0.01),单支病变组FMD高于三支病变组(P0.05)。多元回归分析显示,FMD是诊断冠心病的独立预测因素(OR=0.182,95%CI为0.068~0.487,P0.01)。ROC曲线分析显示,FMD≤6.05%是预测冠状动脉病变最佳界值,其敏感性为91.1%,特异性为80.4%,阳性预测值为87.8%,阴性预测值为85.4%。结论 FMD可较好地反映冠状动脉病变程度,对冠心病的诊断具有较好的预测价值。     

Evaluation of the Impact of Treatment on Endothelial Function and Cardiac Performance in Acromegaly

Objective: To evaluate the effects of treatment on left ventricular (LV) performance and endothelial function in patients with acromegaly. Method: Nineteen patients with active acromegaly (AA), 18 patients with cured/well‐controlled acromegaly (CA), and 25 healthy control subjects were studied. LV performance was evaluated by two‐dimensional/Doppler echocardiography and Doppler tissue imaging (TDI). Flow‐mediated dilatation (FMD) was measured by B‐mode ultrasound. Endothelial cell markers; thrombomodulin (TM), and P‐selectin were also measured. Results: Tei index was higher than the control subjects in both acromegaly groups. The ratio of early and late diastolic annular velocities (Em′/Am′) was significantly lower in the AA group than the other groups (P < 0.05). FMD in both acromegaly groups was significantly lower than the controls (P < 0.001) but difference between acromegaly groups was not significant (P > 0.05). In the CA group, P‐selectin was higher than the controls and was even higher in the AA (P < 0.05). TM was significantly higher in the active group (P < 0.05) and not different than the controls in the CA group. Conclusion: TDI determine LV performance changes in acromegaly earlier than conventional echocardiographic methods. Endothelial function both in the form of FMD and endothelial cell markers is impaired in acromegaly. While in cured acromegaly endothelial cell injury, as evidenced by TM levels, is decreased, endothelial dysfunction still persists. (Echocardiography 2010;27:990‐996)     

Radial artery flow‐mediated dilation predicts arterial spasm during transradial coronary interventions

Background : Transradial coronary catheterization has emerged over the last years as a favorable catheterization practice, based on evidence that it is associated with less vascular complications and shorter hospital stays. However, access site crossover appears to be more frequent when the initial route is the transradial one, one of the main reasons being arterial spasm. We hypothesized that radial flow‐mediated dilation (FMD) measurements could be used as a preprocedural method to assess the likelihood of arterial spasm. Methods : The study population consisted of patients scheduled for transradial diagnostic catheterization in whom ad hoc percutaneous coronary intervention (PCI) was performed. FMD was measured 1–2 days before PCI. The primary endpoint of the study was operator‐defined (operators were blinded as to the FMD results) radial artery spasm. Results : A total of 172 patients (110 male, age 65.3 ± 9) were included. Radial artery spasm was recorded in 13 patients (7.6%). FMD showed a very significant univariate association with the occurrence of spasm (P < 0.001) and was the most important predictor of spasm in the multivariate logistic regression analysis (beta ?3.15; P < 0.001), followed by baseline radial artery diameter (P = 0.04), the number of catheters used (P = 0.049) and the administered volume of contrast medium (P = 0.017). Conclusion : Preprocedural FMD is a significant predictor of arterial spasm before elective transradial PCI. It is a low cost, safe, and feasible noninvasive modality, whose results might be taken into account when deciding on the vascular access route for an elective procedure, the size of sheaths or catheters to be used or the intensity of antispasm medication.© 2010 Wiley‐Liss, Inc.     

Relationship between endothelial function in the coronary and brachial arteries

BACKGROUND: Endothelial dysfunction is the first step in the progression to atherosclerosis, but little is known regarding whether there is a correlation in endothelial function between the coronary and peripheral arteries. HYPOTHESIS: We investigated the relationship between coronary and peripheral endothelial function. METHODS: In 41 patients (mean age 63 years; 23 men, 18 women) with angiographically normal coronary arteries, changes in brachial artery diameter in response to hyperemic flow and sublingual nitroglycerin (NTG) were measured by high-resolution ultrasonography. During coronary angiography, acetylcholine (ACh, 3 and 30 microg/min) and NTG were infused into the left coronary ostium. The diameter of the coronary artery was quantitatively measured and coronary blood flow (CBF) was calculated by quantitative angiography and Doppler flow velocity measurements. Changes in these parameters in response to each drug infusion were expressed as the percent change from the baseline values. RESULTS: Flow-mediated dilation (FMD) of the brachial artery was 5.0 +/- 3.5% and correlated positively not only with the change in coronary diameter (ACh at 30 microg/min, r = 0.31, p < 0.05) but also with the change in CBF (ACh at 3 microg/min, r = 0.39, p < 0.05; ACh at 30 microg/min, r = 0.46, p < 0.01). Multivariate analysis demonstrated that FMD was one of the factors associated with the changes in coronary diameter and CBF. CONCLUSIONS: These results suggest that brachial endothelial function is associated with coronary endothelial function in patients with angiographically normal coronary arteries, suggesting that impairment of endothelial function may occur simultaneously in both coronary and peripheral arteries.     

高血压患者内皮脂肪酶与肱动脉血流介导的内皮依赖性血管舒张功能的关系

目的观察高血压患者内皮脂肪酶(EL)的变化,并探讨其与肱动脉血流介导的内皮依赖性血管舒张功能(FMD)的关系。方法入选初诊原发性高血压(EH)患者(EH组,n=132)和血压正常的健康体检者(对照组,n=118)为受试者,测量两组研究对象的身高、体质量、血压,检测空腹血糖、总胆固醇、三酰甘油、低密度脂蛋白胆固醇(LDL-C)和高密度脂蛋白胆固醇(HDL-C),用酶联免疫吸附法检测血浆EL的水平,用超声技术检测FMD,分析EL与FMD的相关性。结果EH组血浆EL水平明显高于对照组[(468.3±50.7)比(235.0±24.9)μg/L,P<0.05],FMD显著低于对照组[(7.2±2.1)%比(12.3±2.4)%,P<0.05],而且,随着高血压分级的增加,EL水平逐步升高,但是FMD逐渐下降(趋势均P<0.05)。对EH组进行Pearson相关分析显示FMD与收缩压、舒张压、体质量指数(BMI)、空腹血糖、总胆固醇、三酰甘油、LDL-C和EL呈负相关,与HDL-C呈正相关(均P<0.05)。多元线性逐步回归显示,校正年龄、性别、血压、血脂、血糖等因素后,EL是FMD的影响因素(P<0.05)。结论高血...     

Correlation of flow mediated dilation with inflammatory markers in patients with impaired cardiac function. Beneficial effects of inhibition of ACE

Impaired cardiac function is frequently accompanied by peripheral vascular dysfunction and a pro-inflammatory condition, which may be associated with elevated levels of angiotensin II. We hypothesized that the magnitude of flow mediated dilatation (FMD) of the brachial artery of post myocardial infarction patients will correlate with serum levels of tumor necrosis factor alpha (TNFalpha) and C-reactive protein (CRP), and that treatment with angiotensin converting enzyme inhibitors (ACEI) will increase FMD by reducing TNFalpha and CRP. Patients were treated with low dose (10 mg/day) quinapril (Q) or enalapril (E) and their effects on FMD and inflammatory markers were evaluated after 8 and 12 weeks. Before treatment, in both groups FMD showed a low value (Q: 2.95+0.42% and E: 3.3+/-0.33%), whereas TNF-alpha (Q: 31.65+/-8.23 pg/ml and E: 29.5+/-5.9 pg/ml) and CRP (Q: 7.28+/-2.96 mg/ml and E: 7.08+/-3.02 mg/ml) were elevated. In the Q group, but not in the E group FMD increased significantly, (to 5.96+1.10%), whereas TNF-alpha (19.0+/-12.21 pg/ml) and CRP (to 3.91+/-1.82 mg/L) significantly decreased after 8 and 12 weeks of Q treatment. Moreover, the magnitude of FMD showed a strong inverse correlation with serum levels of TNF-alpha and CRP after Q treatment. Thus, in post myocardial infarction patients endothelial dysfunction assessed by FMD correlates with elevated levels of plasma inflammatory markers, and low dose quinapril improves endothelial function, likely by reducing vascular inflammation.