Flow-mediated Dilation In Patients Research Articles

High-dose atorvastatin in peripheral arterial disease (PAD): Effect on endothelial function, intima-media-thickness and local progression of PAD

Beneficial effects of aggressive lipid-lowering with high-dose atorvastatin (80 mg/day) have been demonstrated in patients with coronary and cerebrovascular disease. The impact of such a therapy in patients with peripheral arterial disease (PAD) is less known so far. Here we studied the effects of high-dose atorvastatin on brachial artery endothelial function, common carotid intima-media thickness (IMT) and local progression of PAD in these patients. One hundred of 500 patients screened with documented PAD were randomly assigned to receive 80 mg of atorvastatin daily for six months or to continue on conventional medical treatment. Ninety-six percent of patients in the control group were on standard statin treatment. High resolution B-mode ultrasonography was used to study brachial artery flow-mediated dilation (FMD), IMT and ankle-brachial index (ABI) at baseline and at six months. FMD and IMT at baseline and at six months were 4.1 (0.06-8.6) versus 5.0 (0.76 vs. 8.1) %, p = 0.96, and 0.76 (0.66-0.82) versus 0.73 (0.63-0.81) mm, p = 0.41, respectively, in the atorvastatin group, and 2.66 (-1.9-6.9) versus 3.65 (0.0-8.6)%, p = 0.02, and 0.78 (0.71-0.90) versus 0.77 (0.70-0.90) mm, p = 0.48, in the control group. ABI at baseline and at six months was not different in either group. LDL cholesterol was reduced from 2.53 (2.21-3.28) to 1.86 (1.38-2.29) mM (p < 0.0001) in the atorvastatin group, whereas levels remained stable in the control group [2.38 (1.94-3.16) vs. 2.33 (1.82-2.84) mM, p = 0.61]. Major adverse cardiovascular events occurred in 2.1% in the atorvastatin group and 1.9% in the control group (p = 0.61). In conclusion, in this pilot trial aggressive lipid-lowering with 80 mg of atorvastatin daily for six months had no effect on brachial artery FMD in patients with PAD. IMT and ABI were also similar in patients with and without high-dose atorvastatin at six months.

Impairment of flow-mediated vasodilatation of brachial artery in patients with Cushing’s Syndrome

Cushing's Syndrome (CS) is associated with excess and premature cardiovascular disease. Endothelial dysfunction is the initiating event in the development of atherosclerosis. Endothelial function is assessed by flow-mediated dilatation (FMD) of brachial artery. The aim of this study was to assess FMD in patients with CS. We prospectively evaluated 22 patients with CS (12 women, 10 men; aged 42 +/- 11 years, serum cortisol 28.2 +/- 14 microg/dl, 24-h urinary free cortisol (UFC) 269 +/- 92 microg/day), and 23 control subjects (13 women, 10 men; aged 43 +/- 10 years, serum cortisol 14 +/- 4 microg/dl, 24 h cortisol 60 +/- 22 microg/day). Endothelial function, measured as FMD of the brachial artery using ultrasound, was calculated in two groups. Endothelial function was evaluated by assessing 1-min postischemic FMD of the brachial artery. FMD was lower in patients with CS than that in those without (11.7 +/- 4.8% vs. 15.8 +/- 3.2%, P = 0.0001, respectively). There was no significant difference between two groups regarding baseline diameter of brachial artery. But, hyperemia diameter was lower in patients with CS than without CS (3.6 +/- 0.22 mm vs. 3.9 +/- 0.19 mm, P = 0.04, respectively). Endothelium-dependent FMD may impair in patients with CS compared to controls. Measurement of endothelial function may identify high-risk individuals early and therapy to reduce or retard endothelial dysfunction in patients with CS may lead to decreased cardiovascular morbidity and mortality.

Serum nitric oxide levels and flow-mediated dilatation in patients with Sheehan syndrome and the effect of combination therapy consisting of L-thyroxine, prednisolone, and conjugated estrogen/medroxyprogesterone acetate

Baseline and stimulated nitric oxide (NO) levels were higher, whereas baseline arterial diameter, FMD-stimulated NO increment, and arterial dilatation ratio were lower in Sheehan syndrome (SS) patients than in control subjects. After combination therapy consisting of prednisolone, L-thyroxine, and conjugated estrogen, baseline and stimulated NO levels of SS remained as high, but FMD-stimulated NO, NO increment ratio, and arterial dilatation ratio increased with treatment.

Rheumatic mitral valve stenosis is associated with impaired flow-mediated dilatation

It has been demonstrated that rheumatic mitral valve stenosis (RMVS) is associated with an increase in markers of endothelial dysfunction. It is not known whether this association indicates an impairment of flow-mediated dilatation (FMD) of the vascular endothelium. Thirty patients with RMVS and 30 healthy subjects were studied. FMD in patients with RMVS was significantly smaller than in healthy controls (11.9 ± 0.4% vs 15.4 ± 0.70%, p = 0.003). The absolute change in brachial artery diameter in patients with RMVS was also significantly smaller than in healthy subjects (0.42 ± 0.26 mm vs 0.64 ± 0.32 mm, p < 0.001). These findings suggest that vascular endothelial function is altered in patients with RMVS.

Effects of different intensities of acute exercise on flow-mediated dilatation in patients with coronary heart disease

It is known that regular exercise training improves endothelial dysfunction in coronary artery disease, but, little is known concerning different intensities of acute exercise on endothelial function. We evaluated anaerobic threshold and peak oxygen uptake level of acute exercise on flow-mediated dilatation in patients with stable coronary artery disease. Endothelium-independent vasoreactivity in patients showed a trend with increase at threshold level exercise; however, it was significantly decreased at peak level exercise. Moderate intensity exercise (nearly anaerobic threshold level) should be recommended a therapeutic and preventative strategy for starting of cardiac rehabilitation program in patients with coronary artery disease.

Increased Dilator Response to Nitrate and Decreased Flow‐Mediated Dilatation in Migraineurs

It has been known that in a migraine attack intracranial and extracranial arteries on the headache side dilate and when the migraine attack has subsided, the intracranial arteries show segmental narrowing. We hypothesized that patients with migraine had an underlying systemic vasomotion abnormality and there might be an increased nitrate-mediated vasodilatory response in the brachial artery of migraineurs. Accordingly we aimed to measure endothelium dependent and independent functions of brachial artery in migraineurs and healthy subjects. Twenty-four patients who fulfilled the diagnostic criteria of migraine were enrolled in the study. Twenty-six age- and sex-matched healthy control subjects comprised the control group. Flow-mediated dilatation and nitrate-mediated dilatation were measured in all patients and control subjects by means of brachial artery ultrasonography. Flow-mediated dilatation of patients with migraine was significantly lower than that of control subjects (7.6 +/- 3.7% vs 10.4 +/- 3.5%, respectively, P= .008). However, nitrate-mediated dilatation in migraineurs was significantly higher than that of nonmigraineurs (25% vs 14%, respectively, P< .001). We have shown that migraineurs have decreased endothelium dependent function whereas increased nitrate-mediated response in their brachial artery. It can be suggested that the mechanism underlying migraine may be a diffuse vascular vasomotion abnormalities and migraine may be a local manifestation of systemic vascular abnormality rather than a primary cerebral phenomenon.

Impaired vascular function in patients with Fontan circulation

Background This study was performed to evaluate the endothelial function in Fontan patients, and to investigate the associated factors which influence the endothelial function in these patients. Methods Flow mediated dilatation (FMD) and nitroglycerin induced dilatation (NG) of the brachial artery, and intima media thickness (IMT) of common carotid artery (CCA) were measured in nonselected Fontan patients ( n = 44, age 5 to 29 years, median 14 years, 18 females) by means of high-resolution ultrasound according to the standard protocols. The results were compared to age and sex matched controls ( n = 25, age 5 to 27 years, median 13 years, 10 females). Results Fontan patients presented significantly reduced FMD and NG compared with controls (FMD; 6.5 ± 2.4 vs. 11.1 ± 1.4%, p < 0.001, NG; 13.3 ± 5.2 vs. 19.4 ± 6.2%; p = 0.035). Twenty two percent of Fontan patients presented pure endothelial dysfunction, and 34% of patients presented combined endothelial and smooth muscle dysfunction. Although there was no correlation between FMD and IMT, Fontan patients presented increased carotid IMT (0.44 ± 0.07 vs. 0.38 ± 0.06 mm, p = 0.008). In multivariate analysis, duration of exposure to chronic hypoxia was inversely correlated with FMD ( p = 0.117, hazards ratio = 1.294, 95% confidence interval = 0.938–1.786). There was higher FMD in patients receiving angiotensin-converting enzyme inhibitors (ACEi) compared with those not receiving ACEi (7.0 ± 2.5 vs. 5.5 ± 2.2%, p = 0.069). Conclusions Endothelial dysfunction is more prevalent in Fontan patients compared with healthy controls, and the previous hypoxia is an independent factor. Although it is not statistically significant, those patients on treatment with ACEi seem to have better endothelial function.

Influence of Atorvastatin Treatment on l -Arginine Cerebrovascular Reactivity and Flow-Mediated Dilatation in Patients With Lacunar Infarctions

In our study we hypothesized that statins improve endothelial function in patients with lacunar infarctions (LI). Cerebral and systemic endothelial function was determined before and after 3-months treatment with atorvastatin. Cerebral endothelial function was determined by L-arginine reactivity and systemic endothelial function by flow-mediated dilatation (FMD) in patients with LI (18 patients, aged 61.1+/-7.6 years), 20 age- and gender-matched patients with similar risk factors (SR) and 19 age- and gender-matched healthy controls. The mean arterial velocity (v(m)) in both middle cerebral arteries was measured by transcranial Doppler sonography before, during and after a 30-minute intravenous infusion of L-arginine. FMD of the brachial artery after hyperaemia was determined. The measurements were repeated after 3-months treatment with 40 mg of atorvastatin per day. L-arginine reactivity was decreased in LI patients (13.1+/-8.4%) and in patients with SR compared with healthy controls (P < or = 0.01). FMD was more impaired in patients with LI (0.06+/-4.9%) compared with patients with SR and healthy controls (P < or = 0.01). After atorvastatin treatment, L-arginine reactivity and FMD improved in both patients with LI (17.1+/-7.6%; 7.0+/-5.7%) and patients with SR (P < or = 0.01). Previously mildly increased cholesterol values normalized. The decreased L-arginine reactivity and FMD improve after atorvastatin treatment in both patients with LI and patients with SR.

Statins and Cerebral Vasomotor Reactivity

See related article, pages 2540-2545. Animal models have shown that cholesterol-lowering therapy with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (commonly called statins) may augment absolute cerebral blood flow (CBF) by enhancing nitric oxide synthase (eNOS).1 Statins upregulate type III endothelial eNOS in thrombocytes, decrease platelet activation, and protect from cerebral ischemia in normocholesterolemic mice.2 Statins may also provide additional beneficial effects by upregulating endogenous tissue plasminogen activator and enhancing clot lysis in a mouse model of embolic focal ischemia.3 Statins given 24 hours after experimental ischemia can enhance CBF, angiogenesis, neurogenesis and sinaptogenesis.4 How can these findings be applied in the clinical setting? A meta-analysis of published clinical trials showed that low-density lipoprotein–lowering with statins may decrease the risk of stroke in diabetic or hypertensive patients with normal low-density lipoprotein cholesterol at baseline, and in patients with coronary artery disease, with respectively 48%, 27% and 25% reduction in stroke incidence.5 Does any relationship exist among statins and cerebral vasomotor reactivity? Functional transcranial Doppler (TCD) ultrasonography permits the assessment of cognitively induced CBF velocity changes6 and the evaluation of cerebral vasomotor reactivity.7 TCD can be used to reliably evaluate age-related changes in the physiological response of the human cerebral circulation. A diminished nitric oxide–mediated cerebral vasomotor response may exist in aging subjects and in patients with vascular risk factors.8 Because there are no reliable markers for the functional status of the cerebral small vessels in elderly patients at risk of stroke, TCD studies may be useful. Although some parameters …

Endothelial function in young subjects with vaso-vagal syncope

Background The aim of this study was to determine whether endothelial function and inappropriate peripheral vasomotion have a significant role in the pathogenesis of neurally mediated syncope. Methods In 16 patients (mean age 28.2 ± 5.8 years) with previous vaso-vagal syncope and in matched healthy subjects, endothelium-dependent flow-mediated dilation (FMD) and endothelium-independent response to glyceryl trinitrate (GTN), 25 μg, were measured in the brachial artery from high-resolution ultrasonography. Heart rate variability (HRV) analysis at rest and during tilt test was compared between two groups. Results In the subjects with positive tilt test, all HRV parameters were significant higher respect to subjects with negative tilt test ( P < 0.001). The patients with positive tilt test, showed persistent, marked variability of heart rate (HR), due to increased vagal activity with withdrawal sympathetic tone and consequently reduction of blood pressure (BP) (−30.4 ± 4.2 mmHg, P < 0.001) accompanied by a decrease in HR (−24.3 ± 4.5 beats/min, P < 0.001) compared to negative tilt test subjects. These findings prove the real presence of vagal hypertone in patients with syncope. In our study, HR reached values lower than 40 beats/min. FMD in patients with neurally mediated syncope were significantly greater than those in controls (respectively, 9.2 ± 2.8% vs. 4.6 ± 1.4%, P < 0.01) whereas no differences were shown in the response to GTN (18.4 ± 4.4% vs. 16.1 ± 4.2%, n.s.). Conclusions The augmented endothelial function and the abnormal vasodilation of peripheral arteries in association with bradycardia play an important role in the development of vaso-vagal syncope in young subjects.

Decreased endothelium-dependent vasodilatation in patients with migraine: a new aspect to vascular pathophysiology of migraine

Migraine is a common neurovascular disorder characterized by attacks of severe headache, autonomic and neurological symptoms. We hypothesized that patients with migraine had abnormal endothelial function. The vascular theory of migraine assumes that the major pathophysiological events that initiate the migraine attack occur in the perivascular nerves of the major cerebral vessels. Accordingly, we aimed to measure endothelium-dependent vasodilatation in migraineurs by means of flow-mediated dilatation, which reflects endothelium-dependent vasodilatation capacity. Forty-five patients who fulfilled the diagnostic criteria for migraine and 45 age and sex-matched healthy participants were enrolled in the study. Flow-mediated dilatation of the brachial artery was determined using a high-resolution B-mode ultrasonographic system. Flow-mediated vasodilatation was expressed as the change in post-stimulus diameter as a percentage of the baseline diameter. Mean ages of the patients were 33+/-10 years in migraineurs (range: 18-52 years, 36 female, 9 male) and 33+/-9 years in non-migraineurs (range: 17-50 years, 36 female and 9 male). Flow-mediated dilatation of patients with migraine is significantly lower than that of the controls (8.02+/-4.095% vs. 10.72+/-3.52%, respectively, P=0.001). We have shown that migraineurs have decreased endothelium-dependent vasodilatation capacity compared with non-migraineurs. Migraine may be a local manifestation of systemic vascular vasomotion abnormalities.

Circadian Variation of Endothelial Function in Idiopathic Dilated Cardiomyopathy

This study measured flow-mediated dilation (FMD) of the brachial artery 3 times a day (6:30 a.m., 11:30 a.m., and 9 p.m.) in 7 normal subjects and 14 patients with idiopathic dilated cardiomyopathy (7 in New York Heart Association [NYHA] functional class I or II and 7 in NYHA functional class III or IV). FMD in normal subjects and patients in NYHA class I or II showed a circadian variation, being lowest in the morning and highest at night. Compared with them, FMD in patients in NYHA class III or IV was lower and almost constant during the day, showing loss of significant circadian variation in endothelial function in patients with congestive heart failure.

Counterpoint: Flow-mediated dilation does not reflect nitric oxide-mediated endothelial function

The phenomenon of flow-mediated dilation (FMD) relevant to this debate describes the vasodilation in a conduit vessel in response to elevations in flow-associated shear stress. Nitric oxide (NO) is thought to play a key role in vascular health due to its established vasoprotective characteristics (

Evaluation of Preclinical Atherosclerosis by Flow-Mediated Dilatation of the Brachial Artery and Carotid Artery Analysis in Patients with a History of Kawasaki Disease

Cardiac sequelae of Kawasaki disease are an important cause of ischemic heart disease in young adults. The possibility of early progression of atherosclerosis following Kawasaki disease is therefore of great concern. We examined whether preclinical atherosclerotic changes are seen in patients with a history of Kawasaki disease, and whether these changes appear in all or in only a proportion of patients. Sixty-five patients with a history of Kawasaki disease, aged 13.1 +/- 2.1 years, and 20 aged-matched controls participated in the study. All subjects underwent flow-mediated dilatation (FMD) of the brachial artery and analysis of carotid artery size and pulse-wave transmission. Patients were classified into four groups depending on the severity of the maximum coronary artery lesion: group 0 (normal), group 1 (mild), group 2 (moderate), and group 3 (severe). There was no statistical difference in the carotid artery analyses between the four groups. FMD (mean +/- SD) was significantly lower in groups 2 and 3 than in groups 0 and 1 and the control group (group 0, 19.4 +/- 3.9%; group 1, 19.5 +/-4.1%; group 2, 8.9 +/- 2.8%; group 3, 4.2 +/- 1.5%; control group, 18.8 +/- 2.8%; p < 0.0001). There was a significantly negative correlation between the severity of the coronary artery lesion and FMD (p < 0.0001 for both). Endothelial dysfunction was revealed by FMD in patients with persistent coronary artery lesions subsequent to Kawasaki disease. Preclinical atherosclerosis may be present only in patients with coronary aneurysms.

The Effect of Statin Therapy on Endothelial Function in Type 2 Diabetes Without Manifest Cardiovascular Disease

Cardiovascular disease (CVD) is the most important cause of mortality in patients with type 2 diabetes and is preceded by endothelial dysfunction. Flow-mediated dilation (FMD) is a noninvasive technique for measuring endothelial dysfunction. We aimed to determine the effect of long-term statin therapy versus placebo on FMD in patients with type 2 diabetes without manifest CVD. A randomized, placebo-controlled, double-blind trial was performed with 250 type 2 diabetic patients. Patients were given 0.4 mg cerivastatin or placebo daily. In August 2001, when cerivastatin was withdrawn from the market, the 0.4 mg cerivastatin was replaced by 20 mg simvastatin, without deblinding the study. The primary end point was the change in FMD, measured by B-mode ultrasound, after 2 years. Determinants of baseline FMD were diabetes duration, common carotid intima-media thickness, and brachial artery diameter. FMD at baseline was 1.51% in the placebo group and 1.66% in the statin group and did not change significantly after 2 years. The 2-year statin therapy had no effect on FMD in type 2 diabetes. Statin-induced improvement of cardiovascular risk in patients with type 2 diabetes may be mediated through mechanisms other than increased nitric oxide availability.

Inhibition of angiotensin-converting enzyme and phosphodiesterase type 5 improves endothelial function in heart failure

ACE (angiotensin-converting enzyme) inhibitors and PDE5 (phosphodiesterase type 5) inhibitors have each been reported to improve endothelial function in cardiovascular disease patients, but the comparative and combined effects of these two classes have not been studied previously. We sought to characterize the acute effects of ramipril alone, sildenafil alone, or their combination on endothelial function in patients with CHF (chronic heart failure). CHF subjects (n=64) were randomized to receive placebo, 10 mg of ramipril alone, 50 mg of sildenafil alone or a combination of ramipril and sildenafil in a double-blind manner. FMD (flow-mediated dilation) of the brachial artery was determined by high-resolution ultrasound imaging before and at 1, 2 and 4 h after administration of the study drug. Ramipril alone increased FMD at 4 h compared with placebo (+2.3+/-1.3%, P=0.02). Sildenafil alone increased FMD at 1, 2 and 4 h compared with placebo (+3.9+/-1.4, +4.6+/-1.8 and +3.7+/-1.3% respectively, all P<0.02). Sildenafil in combination with ramipril increased FMD at 1, 2 and 4 h when compared with placebo (+3.5+/-1.5, +4.5+/-1.8 and +4.8+/-1.3% respectively, all P<0.03). Ramipril and sildenafil both acutely improved FMD in patients with CHF, with additive effects evident at 4 h during combination therapy. Therefore further work to characterize chronic effects of combined ACE and PDE5 inhibition on endothelial function are warranted.

The Effect of Ciprofibrate on Flow-Mediated Dilation and Inflammatory Markers in Patients with Combined Hyperlipidemia

Impairment of flow-mediated dilation (FMD) has been shown to be associated with hypercholesterolemia and hypertriglyceridemia and reduction of cholesterol and/or triglyceride levels can improve FMD. In hyperlipidemia the role of inflammatory substances on endothelial function requires further clarification. In patients with combined hyperlipidemia (n = 29), the capacity of FMD was weaker whereas the levels of interleukin (IL)-lalpha, tumor necrosis factor alpha (TNFalpha), soluble intercellular adhesion molecule (sICAM), and fibrinogen were higher compared to normolipemic controls with normal FMD adjusted for age and sex. Patients were randomized to a diet-only or to a ciprofibrate treatment group. After 8 weeks FMD levels rose significantly both in the diet-only (10.2%) and the ciprofibrate treatment (79.4%) groups. In the diet-only group improvement of FMD was significantly associated with the reduction of triglyceride (by 15.9%) and cholesterol (6.9%) levels. The much larger improvement of FMD due to ciprofibrate therapy was accompanied by significant reductions of cholesterol (by 14.4%), fibrinogen, IL-1alpha, and sICAM levels and by significant increase of high-density lipoprotein (HDL) cholesterol concentration, but the change in FMD correlated only with the reduction of the cholesterol level. In line with previous data the authors emphasize that improvement of FMD in patients with combined hyperlipidemia treated with diet and/or ciprofibrate is linked directly to the reduction of cholesterol and triglyceride concentrations rather than to changes in the level of the investigated inflammatory markers.

Vascular endothelial function and plasma homocysteine levels in Behcet's disease

The purpose of the present study was to test endothelial function and to determine if plasma homocysteine levels are associated with endothelial injury in patients with Behcet's disease (BD). Flow-mediated dilation in patients with BD was smaller than that of control subjects (p = 0.001), and mean plasma homocysteine levels in patients with BD were significantly higher (p = 0.0001). On regression analysis, only mean plasma homocysteine concentration was independently related to flow-mediated dilation (F = 5.7, p = 0.001).

Effect of Xiongshao Capsule on the function of vascular endothelium of patients with cervical atherosclerosis

Objective:To study the effect of Xiongshao Capsule (XSC), a TCM herb that can promote blood circulation to remove blood stasis, on the endothelial dependent relaxation function, serum nitric oxide (NO), and plasma endothelin-KET-1) of the patients with cervical atherosclerosis.Methods: Forty patients were randomly divided into two groups: XSC group and Probucol group (western medicine control). In addition, 20 healthy people were set as a normal control group. Plasma ET-1, serum NO, the internal diameter of basal brachial artery, endothelial dependent flow mediated dilation (FMD) and non-endothelial dependent nitroglycerin induced dilation (NID) to the trial group before and after therapy and to the healthy control group were determined respectively. Results: Compared to the healthy control group, FMD of patients with atherosclerosis was damaged obviously, the serum NO level decreased, plasma ET-1 increased (P 0.05). After the patients with atherosclerosis were treated with Xiongshao Capsule for 12 weeks, FMD increased evidently, plasma ET-1 decreased, serum NO and the ratio of NO/ET-1 increased, compared with the level before therapy and Probucol group, the difference was significant (P 0.05).Conclusion: XSC could regulate vascular activity factor and improve the function of endothelial dependent vascular dilation of patients with atherosclerosis.

External counterpulsation therapy improves endothelial function in patients with refractory angina pectoris

ObjectivesThe goal of this study was to investigate the influence of short-term external counterpulsation (ECP) therapy on flow-mediated dilation (FMD) in patients with coronary artery disease (CAD). BackgroundIn patients with CAD, the vascular endothelium is usually impaired and modification or reversal of endothelial dysfunction may significantly enhance treatment. Although ECP therapy reduces angina and improves exercise tolerance in patients with CAD, its short-term effects on FMD in patients with refractory angina pectoris have not yet been described. MethodsWe prospectively assessed endothelial function in 20 consecutive CAD patients (15 males), mean age 68 ± 11 years, with refractory angina pectoris (Canadian Cardiovascular Society [CCS] angina class III to IV), unsuitable for coronary revascularization, before and after ECP, and compared them with 20 age- and gender-matched controls. Endothelium-dependent brachial artery FMD and endothelium-independent nitroglycerin (NTG)-mediated vasodilation were assessed before and after ECP therapy, using high-resolution ultrasound. ResultsExternal counterpulsation therapy resulted in significant improvement in post-intervention FMD (8.2 ± 2.1%, p = 0.01), compared with controls (3.1 ± 2.2%, p = 0.78). There was no significant effect of treatment on NTG-induced vasodilation between ECP and controls (10.7 ± 2.8% vs. 10.2 ± 2.4%, p = 0.85). External counterpulsation significantly improved anginal symptoms assessed by reduction in mean sublingual daily nitrate consumption, compared with controls (4.2 ± 2.7 nitrate tablets vs. 0.4 ± 0.5 nitrate tablets, p <0.001 and 4.5 ± 2.3 nitrate tablets vs. 4.4 ± 2.6 nitrate tablets, p = 0.87, respectively) and in mean CCS angina class compared with controls (3.5 ± 0.5 vs. 1.9 ± 0.3, p <0.0001 and 3.3 ± 0.6 vs. 3.5 ± 0.5, p = 0.89, respectively). ConclusionsExternal counterpulsation significantly improved vascular endothelial function in CAD patients with refractory angina pectoris, thereby suggesting that improved anginal symptoms may be the result of such a mechanism.