Predictive value of noninvasively determined endothelial dysfunction for long-term cardiovascular events and restenosis in patients undergoing coronary stent implantation: a prospective study

BACKGROUND: Endothelial dysfunction plays a key role in atherosclerosis and predicts future cardiovascular events in individuals with or without coronary artery disease and improves with risk reduction therapy. We sought to determine the predictive value of endothelial dysfunction for long-term cardiovascular events and in-stent restenosis in patients undergoing percutaneous coronary intervention (PCI). METHODS: Using high-resolution ultrasound, we assessed endothelial function by using the brachial artery flow-mediated dilation (FMD) method in 135 patients with coronary artery disease before elective coronary stenting. Patients were prospectively followed up for an average of 12 months after PCI. RESULTS: Thirty patients had an event during follow-up including cardiac death (four patients), myocardial infarction (nine patients), unstable angina/non-ST elevation myocardial infarction (15 patients), and stroke (two patients) and in-stent restenosis was determined in 16 of these patients. Endothelium-dependent FMD was significantly lower in patients who had an event compared with those without an event (4.7+/-1.9 vs. 6.0+/-2.0%, P=0.007), whereas endothelium-independent vasodilation to nitroglycerin was similar in both groups. FMD was the only predictor of cardiovascular events (P=0.03). Impaired endothelial function was associated with a significantly higher incidence of cardiovascular events and in-stent restenosis by Kaplan-Meier analysis. When a cutoff point of 7.5% was used, flow-mediated dilation had a sensitivity of 93%, specificity of 37%, and negative predictive value of 95% for cardiovascular events. CONCLUSION: Impaired brachial artery FMD is associated with long-term cardiovascular events and in-stent restenosis in patients undergoing PCI. Noninvasive assessment of endothelial function may serve as a surrogate marker for the estimation of future cardiovascular event risk and long-term follow-up in these patients.     

Baroreflex sensitivity normalization after cardiac resynchronization therapy

To evaluate the relation between peripheral vascular endothelial function and coronary flow reserve (CFR), we assessed flow mediated dilation (FMD) of brachial artery and the intima-media thickness (IMT) of the carotid artery in 32 subjects (mean age 58+/-9 years, M/F=9:23 ) with chest pain and normal coronary angiogram. The subjects were divided into 2 groups according to CFR >or=2.1 or <2.1 measured with transthoracic echocardiography in distal left anterior descending coronary artery. We found % FMD was decreased in the group with CFR <2.1 than those of CFR >or=2.1 and CFR was correlated with peripheral FMD. However, IMT was not different between two groups. These results suggest that microvascular dysfunction is primarily related to endothelial dysfunction rather than advanced atherosclerosis and because it is a generalized process that involves the whole arteries, the measurement of brachial FMD can be a useful diagnostic tool to evaluate microvascular dysfunction in patients with chest pain and normal coronary angiogram.     

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.     

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)     

Large brachial artery diameter is associated with angiographic coronary artery disease in women

Background Noninvasive methods are needed for the identification of women at highest risk for coronary artery disease (CAD) who might benefit most from aggressive preventive therapy. Identification of brachial artery atherosclerosis, which correlates with coronary artery atherosclerosis, may be useful to estimate or stratify CAD risk. Because atherosclerosis disrupts the arterial architecture that regulates vessel size, we hypothesized that noninvasively measured large brachial artery diameter is a manifestation of atherosclerosis that is associated with angiographic CAD in women with chest pain. Methods We examined 376 women (mean age, 57.1 years) with chest pain in the National Heart, Lung, and Blood Institute's Women's Ischemia Syndrome Evaluation study who underwent B-mode ultrasound scan measurement of brachial artery diameter at rest and during hyperemic stress (to quantify flow-mediated dilation), quantitative coronary angiography, and risk factor assessment. Results Large resting brachial artery diameter was associated with significant angiographic CAD (3.90 ± 0.79 mm vs 3.52 ± 0.59 mm in women with CAD vs no CAD; P < .001). Impaired flow-mediated dilation, which correlated with resting diameter (r = −0.17; P = .001), was weakly associated with significant CAD (2.74% ± 7.11% vs 4.48% ± 9.52% in CAD vs no CAD; P = .046). After adjustment for age, body size, and CAD risk factors, women with large resting brachial artery diameters (>4.1 mm) had 3.6-fold increased odds (95% confidence interval, 1.8 to 7.1; P < .001) of significant angiographic CAD compared with those with small brachial arteries (≤3.6 mm). Conclusion Large resting brachial artery diameter is an independent predictor of significant CAD in women with chest pain. Therefore, a simple ultrasonographic technique may be useful in the identification of women with chest pain who are at increased risk for CAD. (Am Heart J 2002;143:802-7.)     

Flow-mediated vasodilation of the femoral and brachial artery induced by exercise in healthy nonsmoking and smoking men.

OBJECTIVES: We sought to analyze diameter changes of conduit arteries in response to whole-body exercise and hypothesized that this response might be endothelium-dependent and, therefore, impaired in smokers. BACKGROUND: Hyperemia and coincident vasodilation are pivotal mechanisms for meeting the increased metabolic demands of active muscle tissue during physical exercise, but studies in humans are sparse. METHODS: We studied diameter and blood flow of the femoral and brachial arteries in response to a submaximal bicycle exercise test in 10 nonsmoking and 8 smoking healthy male subjects. During an exercise period of 40 min the investigated conduit arteries were periodically scanned in longitudinal sections by high-resolution ultrasound. In the same subjects flow-mediated dilation (FMD) of the brachial artery was recorded by inducing an ischemia through a forearm-occluding cuff. RESULTS: In response to exercise the diameter of the femoral artery significantly increased in both nonsmokers and smokers, with a diminished response in smokers (9.2 +/- 1.9% vs. 4.8 +/- 1.6%, p < 0.001). Flow-mediated dilation of the brachial artery induced by forearm occlusion was also reduced in smoking subjects, revealing a strong correlation between these different methods of FMD (exercise vs. forearm ischemia) (r = 0.88, p < 0.001). In contrast, blood flow increase of the femoral artery was similar in nonsmoking and smoking subjects (392 +/- 77% vs. 382 +/- 109%, p = NS). CONCLUSIONS: Conduit arteries react with a flow-mediated dilation in response to whole-body exercise. The impairment of this vasodilation observed in smokers was strongly related to a decrease of endothelium-dependent dilation induced by forearm ischemia, indicating that endothelial dysfunction represents the underlying mechanism.     

Vascular endothelial dysfunction is associated with reversible myocardial perfusion defects in the absence of obstructive coronary artery disease.

BACKGROUND: The purpose of this study was to investigate whether endothelial dysfunction contributes to abnormal myocardial perfusion imaging (MPI) observed in patients without obstructive coronary artery disease (CAD). It is unclear whether reversible MPI defects detected in the absence of obstructive CAD represent underlying vascular pathology or are false-positive MPI results. Recent evidence suggests that coronary endothelial dysfunction might play a role in the pathogenesis of these defects. METHODS AND RESULTS: We prospectively recruited 36 patients with chest discomfort, reversible abnormalities on MPI, and nonobstructive or absent CAD (stenosis <50% on coronary angiography). The control group (n = 55) consisted of patients with chest discomfort and similar cardiac risk factors but with normal MPI findings. Vascular endothelial function was assessed in the brachial artery by ultrasound as the response to hyperemia and reported as percent flow-mediated dilation (FMD). Response to sublingual nitroglycerin was used as an indicator of endothelium-independent vasodilation. The patients with abnormal MPI findings and nonobstructive CAD had a significantly lower FMD (9.0% +/- 7.2%), indicating endothelial dysfunction, compared with those with similar risk factors and normal MPI findings (12% +/- 5.2%) (P = .03). Baseline brachial artery size and endothelium-independent dilation were similar between groups. On multivariate analysis, only endothelial dysfunction was predictive of reversible MPI defects. CONCLUSIONS: Patients with chest pain and reversible MPI defects but without obstructive CAD have lower FMD indicative of endothelial dysfunction, as compared with similar patients with normal MPI findings. The possibility of a causal link between reversible MPI defects and endothelial dysfunction needs further exploration.     

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.     

Effect of tirofiban on percutaneous coronary intervention-induced endothelial dysfunction in patients with stable coronary artery disease

Recent studies demonstrated that glycoprotein (GP) IIb/IIIa receptor antagonists improve endothelial dysfunction of forearm resistance vessels in patients with stable coronary artery disease. However, it remains unclear whether these findings can be extended to the conductance vessel level. In this study, we aimed to evaluate the acute effect of tirofiban on endothelial function of arterial conductance vessels in patients undergoing percutaneous coronary intervention (PCI). Endothelial function was examined by ultrasonographic measurement of flow-mediated vasodilation (FMD) of the brachial artery. Endothelium-independent vasodilation was determined in response to nitroglycerin. Sixty-six patients who underwent PCI were included in the study. Thirty-three patients received a bolus of 10 microg/kg body weight of tirofiban, whereas 33 patients who did not receive tirofiban served as the control group. FMD was measured in all patients before and 30 minutes after PCI. Tirofiban significantly improved FMD (6.0 +/- 0.4% before vs 7.8 +/- 0.5% after PCI, p <0.0001), whereas FMD deteriorated in patients in the control group (6.1 +/- 0.6% before vs 4.7 +/- 0.7% after PCI, p = 0.006). Nitroglycerin-induced dilation remained unaltered in response to PCI. In another group of 11 patients with coronary artery disease, FMD did not change after coronary angiography without coronary intervention. In conclusion, PCI induces endothelial dysfunction in forearm conductance vessels that can be reversed with tirofiban.     

培垛普利对冠心病患者经皮冠状动脉介入术后肱动脉内皮功能障碍的影响

目的探讨培垛普利对经皮冠状动脉介入（PCI）操作所诱发的肱动脉内皮功能不全的影响。方法实行PCI的冠心病患者62例,随机分为2组,培垛普利组31例,对照组31例,应用高频超声探头分别测量2组PCI术前及术后的肱动脉基础内径、反应性充血内径、含服硝酸甘油后内径,计算肱动脉血流介导的舒张反应（FMD）,并运用多普勒技术测定血流速度峰值,最后比较2组间及组内上述参数的差异。超声测量于PCI术前2h和术后30min内完成。结果培垛普利组的FMD明显改善[（5．9±0．3）％术前vs（7．7±0．4）％术后PCI,P〈0．0013,而对照组明显恶化[（6．0±0．5）％术前vs（4．8±0．6）％术后PCI,P〈0．0013。两组硝酸甘油介导的血管舒张反应及反应性充血血流速度峰值均无明显变化。结论培垛普利可改善PCI介导的肱动脉内皮功能不全。     

Morning attenuation of endothelium-dependent,flow-mediated dilation in healthy young men: Possible connection to morning peak of cardiac events?

BACKGROUND AND HYPOTHESIS: Brachial artery flow-mediated dilation (FMD), a noninvasive, widely used clinical index of endothelial function and magnitude of FMD, has been reported to be closely related to many coronary risk factors and coronary atherosclerosis. However, there has been no study that examines the diurnal change of FMD. We designed this study to reveal the diurnal variation of FMD in healthy volunteers. METHODS: We examined FMD in response to reactive hyperemia by high resolution ultrasound in 13 healthy young men (age 25-32) at four different times over the course of a day. RESULTS: Mean measures of brachial artery FMD was 4.0% at 8:00, 5.3% at 12:00, 9.7% at 17:00, and 6.9% at 21:00 hours. Flow-mediated dilation at 8:00 and at 12:00 hours was significantly lower than that at 17:00 (p < 0.05). CONCLUSIONS: These results show that endothelial function has diurnal variation and is significantly attenuated in the morning. Morning attenuation of endothelial function should be recognized in clinical research and may play an important role in the circadian variation of the occurrence of acute cardiovascular events.     

Correlation of endothelial function in large and small arteries in human essential hypertension

OBJECTIVES: The structure and function of blood vessels varies along the vascular tree, and alterations found in hypertension are also different. The aim of this study was to determine whether non-invasive measurement of endothelial function in conduit arteries reflects that of subcutaneous resistance arteries measured in vitro. METHODS AND RESULTS: Sixteen essential hypertensive patients (aged 50 +/- 2 years) were studied. Flow-mediated dilation (FMD) during reactive hyperemia (endothelium-dependent) and sublingual nitroglycerin (NTG)-induced dilatation (endothelium-independent) were assessed in brachial arteries by ultrasound. Structure, and acetylcholine (10(-9) to 10(-4) mol/l) and sodium nitroprusside (SNP, 10(-8) to 10(-3) mol/l)-induced vasorelaxation of resistance arteries dissected from gluteal subcutaneous biopsies were measured in vitro using a pressurized myograph. Brachial artery FMD and NTG-induced dilatation were 8.4 +/- 1.0 and 18.1 +/- 1.4%, respectively. Resistance arteries of hypertensive patients showed greater media:lumen ratio (8.6 +/- 0.4 versus 5.9 +/- 0.3% in normotensive subjects, P< 0.01), and maximal acetylcholine responses was diminished to 75 +/- 6% compared to normotensive subjects (97 +/- 2%, P< 0.01). FMD correlated with maximal acetylcholine responses (r2 = 0.57, P< 0.001). FMD did not correlate significantly with the media: lumen ratio of resistance arteries (r2 = -0.22, P= 0.07). By multivariate analysis, FMD predicted resistance artery endothelial function independently of age, sex, body mass index, blood lipid status and lumen diameter of brachial artery (beta = 0.81, P< 0.001). CONCLUSIONS: Endothelial dilatory responses are similar in large and small arteries in hypertensive patients. Abnormal FMD in the brachial artery predicts the presence of endothelial dysfunction in human resistance arteries, suggesting that impairment of endothelial function is a generalized alteration in hypertension. Ultrasound measurement of endothelial dysfunction in the brachial artery appears to be less sensitive than in-vitro measurement in resistance arteries.     

Treatment of in-stent restenosis with sirolimus-eluting-stents -- a six month clinical and angiographic follow-up

Summary Treatment of in-stent restenosis (ISR) remains a therapeutic challenge since many pharmacological and mechanical approaches have shown disappointing results except for brachytherapy. Drug-eluting stents (DES) have been reported to effectively reduce ISR in de novo lesions. We studied 55 consecutive patients with ISR in native coronary arteries and 7 with ISR in saphenous vein grafts (SVG) with elective indication for percutaneous coronary intervention (PCI), who underwent successful implantation with DES. No in-hospital postprocedural major adverse cardiac events were observed. All but one patient (n=61) underwent an angiographic follow-up at 183±30 days. Grade of stenosis was assessed by quantitative coronary angiography (QCA) at index procedure and at control angiography. Restenosis (>50%) occurred in 5 patients (8.2%). Target vessel revascularization was performed in an additional 4 patients. Minimal intimal hyperplasia was observed in all segments covered by DES (late loss 0.08±0.37 mm, loss index 0.11±0.47). One patient suffered from subacute stent thrombosis due to discontinuation of clopidogrel medication. At six month follow-up two patients had died. Death was not related to a restenosis in the treated segment. Conclusion Our experiences with DES treatment of ISR lesions show good angiographic and clinical results at index procedure and at the 6 month follow-up with low sub acute thrombosis rate as compared with existing treatment modalities. Restenosis rate seems to be at least as low as reported for brachytherapy.      

Relation of brachial artery flow-mediated vasodilation to significant coronary artery disease in patients with peripheral arterial disease

In patients at risk for coronary atherosclerosis, brachial artery flow-mediated dilation (FMD) rules out significant coronary artery disease (CAD). However, the value of this approach is unknown in patients with peripheral arterial disease who are at increased risk for CAD. This study assessed whether the noninvasive evaluation of endothelial function by brachial artery FMD rules out significant CAD by dipyridamole myocardial perfusion imaging (MPI) in patients with peripheral arterial disease who are asymptomatic for CAD. Forty-four patients with peripheral arterial disease who were asymptomatic for CAD underwent, in the same day, FMD evaluation and dipyridamole MPI using technetium-99m sestamibi single photon-emission computed tomography. MPI results were abnormal in 17 of 44 patients (39%). FMD was significantly less (6.0 +/- 2.3%) in patients with abnormal MPI results compared with those with normal MPI results (7.3 +/- 1.8%, p = 0.04). By multivariate analysis, FMD was the only significant predictor of abnormal MPI results (odds ratio 0.63, p = 0.02). Receiver-operating characteristic curve analysis assessing the ability of FMD to identify patients with summed stress scores > or =3 yielded an area under the curve of 0.74 (p = 0.009). A FMD value >6% provided 92% negative predictive power to rule out abnormal MPI results, with sensitivity of 79% and specificity of 73%. In conclusion, the noninvasive evaluation of endothelial function by FMD has high negative predictive accuracy and good sensitivity and specificity to detect abnormal MPI results in patients with peripheral arterial disease. Thus, it may represent a valuable screening test to rule out significant CAD in these patients.     

Fibromuscular dysplasia of the coronary and renal arteries?

Fibromuscular dysplasia (FMD) involving the coronary arteries has been described pathologically as a cause of myocardial infarction but has not been described antemortem. Unlike renal artery FMD, its clinical manifestations remain poorly characterized. We describe demographic, clinical, and coronary angiographic characteristics of seven women with acute coronary syndromes and unusual coronary anatomy who also had renal artery FMD. All subjects were female caucasians, age 42-56, who presented with prolonged chest pain and positive troponin tests. Two were smokers, two had hypertension, and one had hypercholesterolemia. None was diabetic. There were distinctive angiographic features common to all seven patients. The left anterior descending artery was involved in six, the right posterior descending artery in one. In each case, the proximal vessel appeared normal but in the middle or distal segment there was a well-demarcated abrupt transition to diffuse obliterative disease. In six of the cases, this continued distally for the remainder of the epicardial vessel. In no case was revascularization feasible. Unlike severe diffuse atherosclerotic disease, all other coronary segments were angiographically normal. Ventricular dysfunction, if present, was mild. All seven patients had typical angiographic features of renal FMD, three bilaterally. We have observed a characteristic pattern of well-demarcated obliterative coronary artery disease associated with FMD of the renal arteries. All cases presented as acute coronary syndromes in patients at relatively low risk of coronary artery disease. We propose that these appearances in the epicardial arteries, previously undescribed ante-mortem represent coronary artery fibromuscular dysplasia.     

Prognostic value of brachial artery endothelial function and wall thickness.

OBJECTIVES: We sought to examine the prognostic value of brachial artery (BA) flow-mediated vasodilation (FMD) and intima-media thickness (IMT) in patients admitted for invasive evaluation of chest pain. BACKGROUND: Both FMD and IMT of the BA have been associated with coronary risk factors and the presence of coronary artery disease (CAD). Recent studies on the prognostic value of FMD have been conflicting. METHODS: In 398 consecutive patients (age 54 +/- 9 years) undergoing coronary angiography, FMD and IMT of the BA were measured using high-resolution ultrasound (13 MHz). Patients were divided into two groups according to the FMD median (7.6%). After a mean follow-up of 39 +/- 12 months, cardiovascular events were documented. RESULTS: No difference was found in the number of cardiovascular events between groups. On multivariate Cox regression analysis, including age, number of risk factors, BA diameter, presence of CAD, FMD, and IMT, only the presence of CAD and IMT remained significantly associated with cardiovascular events. CONCLUSIONS: Intima-media thickness predicted late (up to 4 years) cardiovascular events in a large population admitted for evaluation of chest pain. In contrast, the long-term prognostic value of a single baseline measure of BA-FMD seems to be limited.     

Echolucent carotid plaques predict in-stent restenosis after bare metal stenting in native coronary arteries

Echolucent carotid plaque is considered to predict coronary events. This study examined whether echolucent carotid plaque may predict in-stent restenosis (ISR) in coronary arteries. This study included 202 patients who had elective and successful percutaneous coronary intervention (PCI) with bare metal stents in de novo lesions of native coronary arteries for symptomatic coronary artery disease (CAD). Carotid plaque echolucency was assessed by ultrasound with integrated backscatter (IBS) analysis (intima-media IBS value minus adventitia IBS) 1 day before PCI. All patients underwent planned coronary angiography (CAG) at 6 months after PCI, or CAG before 6 months due to acute coronary syndromes. ISR (defined as >50% diameter stenosis) was found in 65 (32%) patients. The calibrated IBS values of carotid plaques were inversely correlated with late luminal loss of the stented lesions. Using multivariate logistic regression analysis, the presence of echolucent carotid plaques (相似文献   

Detection of endothelial dysfunction with brachial artery ultrasound scanning

The role of the endothelium in human disease recently has become the focus of intense scientific investigation. Impaired endothelial function is associated with a number of disease states, including cardiovascular disease (CVD) and its major risk factors. Endothelial dysfunction precedes overt vascular disease by years and may itself be a potentially modifiable CVD risk factor. Although no gold standard for the measurement of endothelial function exists, the measurement of flow-mediated dilation (FMD) in the brachial artery, assessed with Doppler ultrasonography, is the most studied method and shows the most promise for clinical application. It is a well-tolerated, noninvasive, and low-risk procedure. Brachial artery FMD after transient vascular occlusion may serve as an index of nitric oxide bioavailability, and its impairment correlates with coronary arterial abnormalities. These factors, with the wide availability of vascular ultrasound scanning in clinical practice, make brachial artery FMD an attractive screening tool for endothelial dysfunction. Present limitations of this procedure include the lack of a consensus definition of normal FMD and the variability among centers in both procedural technique and image analysis. However, these limitations are likely to be overcome with increasing experience and advances in technology, and with further refinements, the measurement of brachial artery FMD will likely become the clinical technique of choice for the evaluation of endothelial disease.     

Peripheral vascular endothelial function testing for the diagnosis of coronary artery disease

Background

Abnormalities in endothelium-dependent vasodilation may be detected in arteries before the development of overt atherosclerosis, and their presence may predict stress-induced ischemia as assessed by ST-segment depression and/or perfusion defects. Brachial artery ultrasound during reactive hyperemia is a noninvasive method of assessing peripheral vasomotion, measured by flow-mediated vasodilation (FMD). The purpose of the current study was to assess whether endothelium-dependent FMD of the brachial artery, by ultrasound imaging, predicts the presence of angiographically assessed coronary artery disease (CAD).

Methods

One hundred ninety-eight in-hospital patients (age, 59 ± 9 years; 78 women) with chest pain syndrome and without previous myocardial infarction or revascularization procedures were enrolled in the present study. All of the patients, at testing time, were not receiving nitrate therapy and underwent, on different days, coronary angiography and endothelium-dependent FMD testing of the brachial artery by high-resolution ultrasound. The result of the flow-mediated dilation (%FMD) is defined as the percent change in the internal diameter of the brachial artery during reactive hyperemia related to baseline. A coronary vessel was considered to have a significant obstruction if its diameter was narrowed by 50% or more on quantitative computer-assisted analysis. A prognostically validated angiographic Duke score (from 0 = normal to 100 = severe left main disease) was calculated.

Results

The %FMD was lower in patients with (n = 69) compared with those without (n = 129) CAD (4.64% ± 4.36% vs 7.39% ± 5.68%; P = .01). By multivariate analysis, the %FMD (P = .01; odds ratio [OR], 1.13; 95% confidence interval [CI], 1.05 to 1.23), male sex (P = .01; OR, 3.47; 95% CI, 1.64 to 7.36), and cigarette smoking habit (P < .01; OR, 4.00; 95% CI, 2.50 to 6.35) were independent predictors of CAD. %FMD was poorly albeit significantly correlated with the severity of CAD (%FMD Duke score, P < .01, r = −0.25). The receiver operator characteristic curve showed the %FMD optimal cutoff value as ≤8.84, with sensitivity of 90%, specificity of 37%, negative predictive value of 90%, and positive predictive value of 43%.

Conclusions

In patients with chest pain, a depressed FMD of the brachial artery was a sensitive indicator of CAD, but it showed poor specificity, and it appeared to be unable to predict both the extent and the severity of angiographically assessed CAD.     

Noninvasive low-frequency ultrasound energy causes vasodilation in humans.

OBJECTIVES: We evaluated the potential vasodilator effects of transcutaneous low-frequency ultrasound (US) in human brachial arteries. BACKGROUND: Recent data show that transthoracic low-frequency US energy results in canine coronary artery vasodilation. METHODS: Brachial artery diameters were measured before and after low-frequency US (29 kHz, 1.4 W/cm2) exposure using US imaging with a linear-array transducer. We assessed the time course of diameter changes after US in 20 subjects. In 10 of 20 subjects, brachial artery flow-mediated vasodilation (FMD) was measured to compare the effect of US to a standard method of evaluating endothelial function. RESULTS: Significant vasodilation was seen after 2 min of US compared with baseline values. At 5 min of US, the brachial artery diameter increased by 4.1%. In addition, the arteries continued to dilate after US exposure. At 3 min after US there was a 5.4%, and at 5 min after US a 6.0% increase in vessel diameter (p < 0.001). These diameters returned to baseline dimensions about 20 min after stopping US. Ultrasound-mediated vasodilation and percentage FMD showed good correlation (r = 0.87; p < 0.001). CONCLUSIONS: This is the first study to demonstrate that noninvasive transcutaneous low-frequency US energy dilates human brachial arteries. This arterial vasodilator effect has a rapid onset (within 2 min), lasts about 20 min, and is similar in magnitude to that of FMD. The vasodilator effect of US may have diagnostic and therapeutic potential in patients with or at risk for vascular disease.