Atherosclerosis impairs flow-mediated dilation of coronary arteries in humans

Studies in animals have suggested that increases in blood flow result in dilation of large arteries by an endothelium-dependent mechanism. Atherosclerosis can impair endothelium-dependent vasodilation to vasoactive agents. The purpose of this study was to determine whether or not large coronary arteries in humans exhibit dilation with increases in blood flow and to test the hypothesis that this response is impaired in the presence of atherosclerosis. Graded concentrations of adenosine were infused into the distal left anterior descending (LAD) coronary artery to test the dilator response of the proximal LAD to increases in blood flow. The proximal LAD was thereby exposed to changes in blood flow, but not directly to adenosine. Ten patients with angiographically smooth proximal LAD segments (group 1) and seven patients with irregularities in the proximal LAD consistent with mild atherosclerosis (group 2) were studied. Infusions of adenosine throughout the range of 0.022 to 2.2 mg/min into the LAD produced a dose-dependent increase in estimated coronary blood flow and a mean increase of 305 +/- 27% at 2.2 mg/min adenosine. At 2.2 mg/min adenosine, a striking difference (p less than 0.001) occurred between the significant flow-mediated dilation of the proximal LAD observed in group 1 (+13.2 +/- 1.3% from 2.63 +/- 0.16 mm, p less than 0.001), and the lack of dilation in group 2 (+1.8 +/- 1.5% from 3.20 +/- 0.17 mm, p = NS), despite a greater increase in coronary blood flow in group 2 (+387 +/- 29%) than in group 1 (+230 +/- 36%).(ABSTRACT TRUNCATED AT 250 WORDS)     

Impact of hypercholesterolemia on acidosis-induced coronary microvascular dilation

An increase in coronary flow conductance during acidosis is an important compensatory mechanism in various diseased conditions. On the other hand, hypercholesterolemia causes microvascular dysfunction as well as macrovascular disorders. We investigated the impact of hypercholesterolemia on the coronary microvascular response to acidosis. Coronary arterioles (< 150 μm) isolated from rabbit hearts were cannulated to micropipettes in a vessel chamber and the microvascular responses were observed. After preconstriction was established, the extravascular pH was gradually reduced from 7.4 to 7.0. The effects of glibenclamide, ATP-sensitive K⁺ (K_ATP) channel blocker, (1 μM, n = 4) or pertussis toxin (100 ng/mL, n = 7) on the acidosis-induced microvascular responses were examined. In another set of experiments, rabbits were randomly assigned to normal chow (NC group, n = 18) or high cholesterol (2 %) diet (HC group, n = 20). After 8 weeks of feeding, the responses of isolated coronary arterioles to acidosis, ADP, nitroprusside, and levcromakalim were examined in the two groups. Coronary arterioles significantly dilated as the pH was reduced and the dilation was significantly inhibited by glibenclamide or pertussis toxin. Acidosis-induced dilation in the HC group was significantly attenuated compared to the NC group (36.5 ± 2.1 % vs 73.7 ± 4.8 % at pH = 7.0 P < 0.05). There were no significant differences in the dilations by ADP, nitroprusside and levcromakalim between the two groups. In conclusion, acidosis-induced dilation of rabbit coronary arterioles is mediated by the activation of the pertussis toxin-sensitive G protein and K_ATP channels, and the dilation of coronary arterioles is impaired in hypercholesterolemia. The impairment occurs upstream of K_ATP channel opening. Received: 19 July 2002, Returned for revision: 1 August 2002, Revision received: 25 September 2002, Accepted: 14 October 2002 Correspondence to: T. Komaru, M.D.     

Investigation of flow-mediated dilation response in normal coronary angiographic patients

Normal findings from coronary angiography do not always show normal endothelial functions. An impaired flow-mediated dilation (FMD) can be a useful marker of the presence of endothelial dysfunction. Hypertension, left ventricular hypertrophy, hypercholesterolemia, and vasospastic angina pectoris can negatively affect FMD response. FMD responses of normal subjects and patients with coronary artery pathology were compared in a prospective cross-sectional study. Patients were divided into 3 groups. Group I patients had a positive exercise stress test and angiographically normal coronary arteries. Group II patients had angiographically significant coronary artery stenosis and stable angina pectoris. Group III had normal results from an exercise stress test and no chest pain. It was concluded that flow-mediated dilation response cannot predict coronary angiographic results. Patients with normal findings from coronary angiography may have impaired endothelial functions.     

高血压肱动脉血流依赖性舒张功能与高尿酸血症的关系

目的 :探讨原发性高血压患者肱动脉血流依赖性舒张功能与高尿酸 (HUA)血症的相关性。方法 :选择 2 2 5例原发性高血压患者 ,5 5例正常人为对照组。应用B超对肱动脉进行扫查 ,在静息、反应性充血时对肱动脉内径进行检测 ,计算不同状态下的管径变化及血流介导的内皮依赖性血管扩张率 (Flow MD % )。将所有对象按Flow MD %大小分成 4个亚组 ,比较各组尿酸情况。结果 :随血尿酸浓度增大 ,Flow MD %逐渐减小 ,尿酸与Flow MD %呈负相关 ,r =- 0 .6 37,P <0 .0 5。结论 :HUA与高血压患者血管壁的早期损害有关系。     

Flow-mediated dilation and gender in patients with coronary artery disease: arterial size influences gender differences in flow-mediated dilation

BACKGROUND: The risk of atherosclerosis and its complications differs between male and female subjects. This is probably associated with gender differences in endothelial function as reflected by endothelium-dependent vasodilation. The aim of the study was to compare flow-mediated dilatation (FMD) in males and females with coronary artery disease (CAD), and to determine factors that might potentially influence FMD. METHODS: Ninety-six patients with stable CAD (CCS II-III): 76 males (mean age: 57.7 +/- 10 years) and 20 postmenopausal females (mean age: 60.1 +/- 10 years) were included into the study. Clinical data, pharmacotherapy, concomitant diseases, and FMD were all assessed. FMD was measured with high-resolution ultrasound as the percent change of brachial artery diameter (BAd) after a 3-minute occlusion (%FMD), and following the administration of 0.4 mg sublingual nitroglycerin (%NTG-MD). RESULTS: The percentage of FMD was significantly decreased (P < 0.05), and BAd was significantly larger (P < 0.001) in males as compared to females. Clinical data, pharmacotherapy, and concomitant diseases were comparable in the study groups.In all subjects examined, %FMD was related to BAd (r =-0.415, P < 0.001) and the percentage of ejection fraction (EF%) (r = 0.325, P < 0.01) in the univariate analysis, and to BAd only (r =-0.343, P < 0.01) in the multivariate analysis. The percentage of nitroglycerine-mediated vasodilatation (NTG-MD) correlated negatively with BAd (r =-0.430, P < 0.001), and positively with EF% (r = 0.334, P < 0.01) in the univariate analysis, and with BAd (r =-0.288, P < 0.05) in the multivariate analysis. Index %FMD x BAd was comparable for male and female subjects. CONCLUSIONS: Males and postmenopausal females with CAD show differences in endothelium-dependent vasodilatation that seem to secondarily result from differences in the BAd. Objective comparison of %FMD is only possible between patients with the same brachial artery size.     

Analysis of differences in flow-mediated dilation in relation to the treatment of coronary patients

INTRODUCTION: Flow-mediated dilation (FMD) is thought to be related to the development of coronary disease. We were interested in knowing the degree of FMD in a large sample of coronary patients in relation to the therapy they were given in clinical practice. PATIENTS AND METHOD: We studied 1,081 coronary patients (age 68 +/- 12 years, 73% male) in which FMD was evaluated in the brachial artery. The patients were classified into 5 treatment groups (416 who receive 2 or more treatments were excluded): group A: 81 controls treated with aspirin, group B: 198 treated with ACE inhibitors, group C: 106 with calcium antagonists, group D: 145 with beta-blockers, and group E: 135 with lipid lowering medication (93% statins). RESULTS: ANOVA was used to analyze the differences between groups. With regard to the number of risk factors present in each group, the patients treated with ACE inhibitors (2.44 +/- 0.79 vs 2.14 +/- 0.89; p < 0.05) and statins (3.45 +/- 0.70 vs 2.14 +/- 0.89; p < 0.05) had more risk factors than GrA and higher levels of LDL-cholesterol (ACE inhibitors 145.0 +/- 33.5 vs 128.5 +/- 32.2 and statins 157.8 +/- 45.3 vs 128.5 +/- 32.2; p < 0.05). GrB had a higher glycemia than controls (123.4 +/- 32.2 vs 114.7 +/- 33.7; p < 0.05). The control group was younger than the therapeutic groups (p < 0.05). Compared with the control group, FMD was significantly higher only in the group treated with ACE inhibitors (3.42 +/- 6.01 vs 0.82 +/- 6.04; p < 0.05). Multivariate logistical regression showed that treatment with ACE inhibitors and statins (p < 0.05) were independent predictors of FMD > 4%. CONCLUSION: Treatment with ACE inhibitors or statins was predictive of the normalization of FMD in coronary patients in clinical practice.     

肱动脉流量介导的舒张超声测定及其临床意义

输送动脉流量介导的舒张(ｆｌｏｗｍｅｄｉａｔｅｄｄｉｌａｔｉｏｎ,ＦＭＤ)具有内皮依赖性,应用高分辨率血管超声测定肱动脉ＦＭＤ活性是近年来国内外研究和反映“血管内皮功能”的重要方法。本期刊登湖南医科大学第二附属医院李向平等大夫的文章“冠心病患者肱动脉内皮依赖性和非内皮依赖性舒张功能的损害”一文涉及了这一问题。对此我们作一简要评价。血管内皮的完整性包括三个方面[1]:(1)保持血管内皮依赖性舒张活性;(2)维护血管内膜无血栓形成表面;(3)维护血管内膜的非增殖状态。因此,临床内皮功能障碍综合征(ｅｎｄｏｔｈｅｌｉａｌ…     

The predictive value of flow-mediated dilation and carotid artery intima-media thickness for occult coronary artery disease

Background: Multidetector row computed tomography (MDCT) is an attractive noninvasive alternative to assess overall coronary artery disease (CAD) burden and may reveal coronary plaques, which may be underestimated by conventional coronary angiography. The aim of this study was to determine whether brachial artery flow‐mediated dilation (FMD) and carotid artery intima‐media thickness (CIMT) might accurately predict patients with occult coronary plaques whose conventional coronary angiographies revealed normal coronary arteries (NCA). Methods: Thirty‐five patients with angiographically NCA were consecutively recruited into the study. They underwent MDCT and were divided into NCA group (18 patients; 8 male; 47 ± 9 years) and occult CAD group (17 patients; 11 male; 50 ± 10 years) according to presence of coronary plaque. Nineteen consecutive patients with evident CAD (16 male; 54 ± 7 years) and 19 healthy subjects (10 male; 50 ± 6 years) were included as control groups. FMD and CIMT were measured by brachial and carotid artery ultrasonography. Results: Occult CAD group had significantly lower FMD and insignificantly higher CIMT than NCA group whereas they had significantly higher FMD and insignificantly lower CIMT than evident CAD group. NCA group had significantly lower CIMT than evident CAD group. Receiver operating characteristic curve analysis demonstrated FMD < 8% (sensitivity: 94.4%; specificity: 73.0%; PPV: 77.3%; NPV: 93.1%) and CIMT ≥ 0.65 cm (sensitivity: 72.2%; specificity: 62.2%; PPV: 65.0%; NPV: 69.7%) could predict patients with CAD. FMD and CIMT were independent predictors of CAD (P < 0.001; OR: 45.630; 95%CI: 5.38–386.983 and P = 0.015; OR: 14.226; 95%CI: 1.666–121.467, respectively). Conclusion: FMD and CIMT might predict patients with occult CAD and be helpful in selecting patients for MDCT. (Echocardiography 2011;28:1141‐1147)     

Effect of bariatric surgery on cardiovascular risk profile

Obesity is associated with increased risk for cardiovascular (CV) disease (CVD) and CV mortality. Bariatric surgery has been shown to resolve or improve CVD risk factors, to varying degrees. The objective of this systematic review was to determine the impact of bariatric surgery on CV risk factors and mortality. A systematic review of the published research was performed to evaluate evidence regarding CV outcomes in morbidly obese bariatric patients. Two major databases (PubMed and the Cochrane Library) were searched. The review included all original reports reporting outcomes after bariatric surgery, published in English, from January 1950 to July 2010. In total, 637 studies were identified from the initial screen. After applying inclusion and exclusion criteria, 52 studies involving 16,867 patients were included (mean age 42 years, 78% women). The baseline prevalence of hypertension, diabetes, and dyslipidemia was 49%, 28%, and 46%, respectively. Mean follow-up was 34 months (range 3 to 155), and the average excess weight loss was 52% (range 16% to 87%). Most studies reported significant decreases postoperatively in the prevalence of CV risk factors, including hypertension, diabetes, and dyslipidemia. Mean systolic pressure reduced from to 139 to 124 mm Hg and diastolic pressure from 87 to 77 mm Hg. C-reactive protein decreased, endothelial function improved, and a 40% relative risk reduction for 10-year coronary heart disease risk was observed, as determined by the Framingham risk score. In conclusion, this review highlights the benefits of bariatric surgery in reducing or eliminating risk factors for CVD. It provides further evidence to support surgical treatment of obesity to achieve CVD risk reduction.     

Impairment of flow-mediated dilation correlates with aortic dilation in patients with Marfan syndrome

Marfan syndrome is an inherited disorder characterized by genetic abnormality of microfibrillar connective tissue proteins. Endothelial dysfunction is thought to cause aortic dilation in subjects with a bicuspid aortic valve; however, the role of endothelial dysfunction and endothelial damaging factors has not been elucidated in Marfan syndrome. Flow-mediated dilation, a noninvasive measurement of endothelial function, was evaluated in 39 patients with Marfan syndrome. Aortic diameter was measured at the aortic annulus, aortic root at the sinus of Valsalva, sinotubular junction and ascending aorta by echocardiography, and adjusted for body surface area (BSA). The mean value of flow-mediated dilation was 6.5 ± 2.4 %. Flow-mediated dilation had a negative correlation with the diameter of the ascending thoracic aorta (AscAd)/BSA (R = ?0.39, p = 0.020) and multivariate analysis revealed that flow-mediated dilation was an independent factor predicting AscAd/BSA, whereas other segments of the aorta had no association. Furthermore, Brinkman index had a somewhat greater influence on flow-mediated dilation (R = ?0.42, p = 0.008). Although subjects who smoked tended to have a larger AscAd compared with non-smokers (AscA/BSA: 17.3 ± 1.8 versus 15.2 ± 3.0 mm/m², p = 0.013), there was no significant change in flow-mediated dilation, suggesting that smoking might affect aortic dilation via an independent pathway. Common atherogenic risks, such as impairment of flow-mediated dilation and smoking status, affected aortic dilation in subjects with Marfan syndrome.     

Use of ultrasound for non-invasive assessment of flow-mediated dilation

The pathological complications of atherosclerosis, namely heart attacks and strokes, remain the leading cause of mortality in the Western world. Preceding atherosclerosis is endothelial dysfunction. There is therefore interest in the application of non-invasive clinical tools to assess endothelial function. The flow-mediated dilation (FMD) test is the standard tool used to assess endothelial function. Reduced FMD is an early marker of atherosclerosis and has been noted for its capacity to predict future cardiovascular disease events. This review discusses the measurement of endothelial function using ultrasound, with a focus on the FMD technique.     

The association of arterial shear and flow-mediated dilation in diabetes

While adjusting flow-mediated dilation (FMD), a measure of vascular function, for shear rate may be important when evaluating endothelial-dependent vasodilation, the relationship of FMD with shear rate in study populations with cardiovascular risk factors is unclear. We aimed to investigate the association of four measures of shear rate (peak shear rate (SR(peak)) and shear rate area under the curve through 30 seconds (SR(AUC 0-30)), 60 seconds (SR(AUC 0-60)), and time to peak dilation (SR(AUC 0-ttp))) with FMD in 50 study subjects with type 2 diabetes and mild hypertension undergoing baseline FMD testing for an exercise intervention trial. Associations among measures of shear rate and FMD were evaluated using Pearson's correlations and R(2). The four measures of shear rate were highly correlated within subjects, with Pearson's correlations ranging from 0.783 (p < 0.001) to 0.972 (p < 0.001). FMD was associated with each measure of shear rate, having a correlation of 0.576 (p < 0.001) with SR(AUC 0-30), 0.529 (p < 0.001) with SR(AUC 0-60), and 0.512 (p < 0.001) with SR(peak). Nine of 50 subjects (18%) did not dilate following the shear stimulus. Among the 41 responders, FMD had a correlation of 0.517 (p < 0.001) with SR(AUC 0-ttp) and similar correlations to those found in the full sample for SR(AUC 0-30), SR(AUC 0-60), and SR(peak). In conclusion, shear rate appears to explain up to a third of between-person variability in FMD response and our results support the reporting of shear rate and FMD with and without adjustment for shear rate in similar clinical populations with CVD risk factors.     

Variability of flow-mediated dilation measurements with repetitive reactive hyperemia

To capture the response of an acute intervention, multiple post intervention measurements of flow-mediated dilation (FMD) must be performed. The effect of repetitive reactive hyperemia on endothelial function and the measurement of FMD are unknown. The purpose of this investigation was (1) to examine the effect of repetitive reactive hyperemia on brachial artery FMD and (2) to determine whether brachial artery FMD is stable during a 2-h morning period. We investigated FMD in 20 apparently healthy college students on three randomized treatment days every 30 min (T30), 60 min (T60), and 120 min (T120) throughout a 2-h morning period (08.00 h to 10.00 h). An ANOVA (p > 0.05) and ICC (> 0.40) were both needed to confirm no difference among repetitive reactive hyperemia treatments. In response to repetitive reactive hyperemia, there was no difference (p = 0.307; ICC > 0.40) within the first and last FMD measurements of each treatment condition or between treatment conditions (p = 0.344; ICC > 0.40). FMD was similar (p = 0.348) throughout the 2-h morning period. In conclusion, repetitive reactive hyperemia over a 2-h period has no effect on FMD measurements in apparently healthy college students. In addition, this study found no time trends for FMD measurements during the 2-h morning period to allow for pre/post intervention FMD measurements.     

Effects of dietary carbohydrate restriction versus low-fat diet on flow-mediated dilation

We previously reported that a carbohydrate-restricted diet (CRD) ameliorated many of the traditional markers associated with metabolic syndrome and cardiovascular risk compared with a low-fat diet (LFD). There remains concern how CRD affects vascular function because acute meals high in fat have been shown to impair endothelial function. Here, we extend our work and address these concerns by measuring fasting and postprandial vascular function in 40 overweight men and women with moderate hypertriacylglycerolemia who were randomly assigned to consume hypocaloric diets (∼1500 kcal) restricted in carbohydrate (percentage of carbohydrate-fat-protein = 12:59:28) or LFD (56:24:20). Flow-mediated dilation of the brachial artery was assessed before and after ingestion of a high-fat meal (908 kcal, 84% fat) at baseline and after 12 weeks. Compared with the LFD, the CRD resulted in a greater decrease in postprandial triacylglycerol (−47% vs −15%, P = .007), insulin (−51% vs −6%, P = .009), and lymphocyte (−12% vs −1%, P = .050) responses. Postprandial fatty acids were significantly increased by the CRD compared with the LFD (P = .033). Serum interleukin-6 increased significantly over the postprandial period; and the response was augmented in the CRD (46%) compared with the LFD (−13%) group (P = .038). After 12 weeks, peak flow-mediated dilation at 3 hours increased from 5.1% to 6.5% in the CRD group and decreased from 7.9% to 5.2% in the LFD group (P = .004). These findings show that a 12-week low-carbohydrate diet improves postprandial vascular function more than a LFD in individuals with atherogenic dyslipidemia.