Arterial elasticity identified by pulse wave analysis and its relation to endothelial function in patients with coronary artery disease

Patients with coronary artery disease (CAD) have impaired endothelial function. Arterial elasticity is modulated by endothelial function. The association between arterial elasticity and endothelial function has not been reported in patients with CAD. The present study was designed to investigate whether endothelial dysfunction contributes to impaired arterial elasticity. Thirty patients with CAD and 30 control subjects were recruited. Large and small artery elasticity indices were non-invasively assessed using pulse wave analysis. Brachial artery endothelium-dependent and -independent function were assessed by vascular response to flow-mediated vasodilation (FMD) and sublingual nitroglyceride (NTG), respectively. C1 large artery elasticity index was not different in the CAD group compared with the control group. However, C2 small artery elasticity index was significantly reduced in the CAD group compared with the control group. Flow-mediated vasodilation (FMD) was also impaired in the CAD group compared with the control group. Flow-mediated vasodilation (FMD) in the brachial artery correlated with C2 small arterial elasticity index. But NTG-mediated brachial artery vasodilation was similar between the two groups. The present findings suggest that the patients with CAD have reduced C2 small arterial elasticity index and impaired FMD. Endothelial dysfunction is involved in diminished arterial elasticity, suggesting that C2 small arterial elasticity index is a novel surrogate measure for the clinical evaluation of endothelial function.     

Antioxidant vitamin C improves endothelial function in obstructive sleep apnea

RATIONALE: Obstructive sleep apnea (OSA) is associated with oxidative stress, endothelial dysfunction, and increased cardiovascular morbidity and mortality. OBJECTIVE: We tested the hypothesis that endothelial dysfunction in patients with OSA is linked to oxidative stress. METHODS: In the present study, we measured flow-mediated dilation (FMD) of the brachial artery by ultrasound in 10 otherwise healthy, untreated patients with OSA and 10 age-and sex-matched control subjects without sleep-disordered breathing before and after intravenous injection of the antioxidant vitamin C. The investigator performing the FMD measurements was blinded to the status of the patients. RESULTS: When compared with control subjects, baseline FMD was significantly reduced in the patients with OSA. After intravenous injection of 0.5 g vitamin C, vasoreactivity remained unchanged in the control subjects. In the patients with OSA, ascorbate led to an increase in FMD to a level comparable to that observed in the control group. CONCLUSION: The reduced endothelial-dependent vasodilation in untreated patients with OSA acutely improves by the free radical scavenger vitamin C. These results are in favor of oxidative stress being responsible for the endothelial dysfunction in OSA. Antioxidant strategies should be explored for the treatment of OSA-related cardiovascular disease.     

Evaluation by high-resolution ultrasonography of endothelial function in brachial artery after Kawasaki disease and the effects of intravenous administration of vitamin C.

Previous studies in patients with a history of Kawasaki disease (KD) have focused on the endothelial function of the coronary arteries and that of the systemic arteries is not fully understood. Furthermore, the effect of vitamin C on systemic vascular endothelial function after KD has not yet been elucidated. In the present study, 39 patients (age, 7.1 +/- 2.7 years) at 1-10 years after acute KD were compared with 17 matched healthy subjects (7.0 +/- 3.1 years). High-resolution ultrasonography was used to analyze brachial artery responses to reactive hyperemia (with increased flow causing endothelium-dependent dilation) and sublingual nitroglycerin (causing endothelium-independent dilation) after KD, and to investigate whether the acute administration of vitamin C can restore systemic endothelial dysfunction. The percent change in diameter of the brachial artery induced by reactive hyperemia in the patients with a history of KD (6.2 +/- 3.9%) was significantly less than that in the control group (14.1 +/- 6.8%, p < 0.0001). No significant difference could be found in the percent change in diameter induced by sublingual nitroglycerin between the controls (33.2 +/- 13.7%) and the patients (30.6 +/- 9.2%, p = 0.49). There was no significant difference in percent change in diameter of the brachial artery induced by reactive hyperemia between the patients who received gamma globulin (6.0 +/- 4.0) and those who did not (7.9 +/- 3.3, p = 0.33). Intravenous infusion of vitamin C significantly increased the percent change in diameter of the brachial artery induced by reactive hyperemia in 19 patients with history of KD (6.6 +/- 3.5% to 13.0 +/- 5.5%, p < 0.0001). After placebo administration in 20 patients with history of KD there was no significant increase in the percent change in the diameter of the brachial artery induced by reactive hyperemia (6.5 +/- 4.5% to 7.3 +/- 4.9%, p = 0.20). The decreased percent change in the diameter of the brachial artery induced by reactive hyperemia in patients with a history of KD compared with the healthy children indicates that systemic endothelial dysfunction exists after KD. Although it is not influenced by early treatment with high-dose gamma globulin in the acute stage of KD, systemic vascular endothelial function can be restored by acute intravenous administration of vitamin C.     

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.     

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

OBJECTIVES: The 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). BACKGROUND: In 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. METHODS: We 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. RESULTS: External 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). CONCLUSIONS: External 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.     

Correlation between flow-mediated vasodilatation of the brachial artery and intima-media thickness in the carotid artery in men

Endothelial dysfunction has been reported to be the initial step in atherosclerosis. A noninvasive technique that uses ultrasound to measure the intima-media thickness of the carotid artery has been applied to evaluate localized atherosclerosis. This study was undertaken to elucidate whether endothelial dysfunction in the brachial artery is related to the intima-media thickness of the carotid artery. Thirty-four men with atherosclerosis (mean+/-SE age 61+/-2 years) and 33 age-matched men without clinical atherosclerosis were examined. The intima-media thickness and plaque formation of the common carotid artery were assessed by B-mode ultrasonography. We also noninvasively measured brachial artery diameter by the same ultrasound machine when the subjects were at rest, during reactive hyperemia, which causes endothelium-dependent vasodilatation, and after sublingual administration of nitroglycerin, which causes endothelium-independent vasodilatation. The atherosclerosis group had a significantly greater intima-media thickness of the common carotid artery than did the control group (1. 02+/-0.04 versus 0.91+/-0.03 mm, P<0.05). The flow-mediated diameter (FMD) increase (percent FMD=DeltaD/D x 100) in the atherosclerosis group was significantly smaller than that in the control group (2. 8+/-0.4% versus 5.1+/-0.6%, P<0.01). A significant negative correlation between the intima-media thickness of the carotid artery and percent FMD was found in all of the subjects. On multiple regression analysis, percent FMD showed a significant negative correlation with the intima-media thickness of the common carotid artery. These findings support the concept that endothelial dysfunction is significantly related to atherogenesis.     

Peripheral Vascular Endothelial Dysfunction in Patients With Angina Pectoris and Normal Coronary Arteriograms

Objectives. We sought to determine endothelium-dependent vasodilator function in the brachial artery of patients with microvascular angina pectoris.Background. Previous studies suggest the presence of endothelial dysfunction of the coronary microcirculation in patients with microvascular angina pectoris. It is not known whether endothelial dysfunction in these patients is a generalized process or whether it is confined to the coronary microcirculation only.Methods. In 11 women (mean [±SD] age 60.1 ± 7.8 years) with microvascular angina (anginal pain, normal epicardial coronary arteries, positive exercise stress test), endothelium-dependent vasodilation was assessed in the brachial artery by measuring the change in brachial artery diameter in response to hyperemic flow. Results were compared with 11 age- and gender-matched patients with known three-vessel coronary artery disease and 11 age- and gender-matched healthy control subjects. In all subjects, the intima–media thickness (IMT) of the common carotid artery was also measured.Results. Flow-mediated dilation (FMD) was comparable in patients with microvascular angina and coronary artery disease (1.9 ± 2.5% vs. 3.3 ± 3.3%, p = NS) but was significantly lower in patients with microvascular angina than in healthy control subjects (1.9 ± 2.5% vs. 7.9 ± 3%, p < 0.05). IMT was significantly lower in patients with microvascular angina than in those with coronary artery disease (0.64 ± 0.08 vs. 1.0 ± 0.28 mm, p < 0.05) and was comparable between patients with microvascular angina pectoris and healthy control subjects (0.64 ± 0.08 vs. 0.56 ± 0.14 mm, p = NS). IMT ≥0.8 mm was observed in 1 of 11 patients with microvascular angina, 1 of 11 control subjects and 10 of 11 patients with coronary artery disease.Conclusions. These findings suggest that endothelial dysfunction in microvascular angina is a generalized process that also involves the peripheral conduit arteries and is similar to that observed in atherosclerotic disease. IMT could be helpful in discriminating patients with microvascular angina and atherosclerotic coronary artery disease.     

高分辨力超声评价川崎病急性期肱动脉内皮功能及维生素C的作用

目的研究川崎病(KD)急性期肱动脉内皮依赖性血管舒张(EDD)功能及快速经静脉输注维生素C的作用。方法应用高分辨力超声分别测定KD急性期患者及对照组反应性充血介导的肱动脉内径百分变化率,并测定快速经静脉输注维生素C后反应性充血介导的肱动脉内径百分变化率。结果KD急性期组反应性充血介导肱动脉内径百分变化率明显低于对照组(P<0.01),其中并发冠状动脉扩张者与未并发冠状动脉扩张者间差异无统计学意义(P>0.05)。KD急性期患者快速经静脉输注维生素C后反应性充血介导肱动脉内径百分变化率较前明显增加(P<0.01)。结论KD急性期外周动脉内皮功能减低,经静脉快速输注大剂量维生素C可以改善KD急性期外周动脉内皮功能。     

Effect of chronic oral supplementation with vitamins on the endothelial function in chronic smokers

Cigarette smoking has been associated with endothelial dysfunction including impaired endothelium-dependent flow-mediated dilation (FMD). In cigarette smokers, increased oxygen-derived free radicals have been suspected of being one of the major causes of endothelial dysfunction, owing possibly to the inactivation of nitric oxide by free radicals. Vitamins C and E are widely used antioxidant vitamins, which have also been reported to effectively improve the endothelial function in several conditions. To test the effect of moderate-term oral antioxidant vitamin supplementation on the endothelial function in smokers, the authors evaluated the combined effect of vitamins C and E, administered in normal dosages, on FMD in young male smokers. A prospective interventional study was performed. In 15 healthy male subjects (mean age, 24.4 +/-2.5 years old). They studied FMD in the brachial artery by using high-resolution ultrasound. The vascular effects of moderate-term oral supplementation with vitamin C (1.0 g/day) and vitamin E (500 mg/day) were determined during reactive hyperemia, which causes endothelium-dependent FMD. They performed a vascular function study 3 times including before vitamin supplement, after 25 days of vitamin supplement, and 4 weeks after the cessation of the vitamin supplement. The flow-mediated dilator response measurements were repeated twice a day before vitamin supplements, and the repeatability obtained from these measurements was found acceptable (variability of FMD <2%). The oral antioxidant vitamin supplement significantly restored FMD (3.8 +/-2.2% vs 5.9 +/-2.5%; p<0.05), however, this effect disappeared 4 weeks after the vitamin supplementations ended. The combined usual dosage of vitamins C and E supplements was found to improve the endothelial function in chronic smokers.     

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.     

Studies on flow-mediated vasodilation and intima-media thickness of the brachial artery in patients with primary hyperparathyroidism

The endothelium is a newly recognized target organ of parathyroid hormone (PTH) and may contribute to its effects on vascular tone and blood pressure regulation. Flow-mediated vasodilation (FMD), brachial and carotid intima-media thickness (IMT) were studied in patients with primary hyperparathyroidism (pHPT) and controls to evaluate endothelial function and structural arterial vessel wall alterations. Sixteen patients with pHPT (mean +/- SEM, age 44 +/- 5 years; PTH 229 +/- 72 ng/L; serum calcium 3.0 +/- 0.06 mmol/L; serum phosphate 2.0 +/- 0.2 mg/L) and 16 normocalcemic control subjects matched for age, sex, and blood pressure were included. Diabetes, hypertension, and vascular disease were excluded in both groups. End-diastolic diameter, flow-mediated (FMD) and nitroglycerin-mediated (NMD) dilation of the brachial artery were measured by a multigate pulsed Doppler system (echo-tracking). IMT was determined using automatic analysis of the M-line signal. Endothelium-dependent FMD was impaired in patients compared to controls (4.6 +/- 1.6% v 19.2 +/- 3.9%, P < .001). NMD (23.8 +/- 3.1% v. 22.4 +/- 2.8%, P = NS), carotid and brachial IMT (0.60 +/- 0.04 mm v 0.64 +/- 0.06 mm, P = NS, and 0.46 +/- 0.04 mm v 0.47 +/- 0.08 mm, P = NS, respectively) and artery diameters were not different. Endothelium-dependent vasodilation is impaired in patients with primary hyperparathyroidism despite normal IMT. Endothelial dysfunction may contribute to increased cardiovascular morbidity and mortality in pHPT.     

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.     

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.     

Cross-sectional study of endothelial function in HIV-infected patients in Brazil

Antiretroviral therapy (ART) in HIV-infected patients has been associated with an increased risk of cardiovascular disease. This study evaluates vascular endothelial dysfunction of the peripheral circulation in Brazilian HIV-infected subjects on ART or naive to ART compared to a control group matched for age and body mass index (BMI). We performed a cross-sectional comparative study to measure postischemic peak flow-mediated dilation (FMD) of the brachial artery and the response to glyceryl trinitrate (GTN) in HIV-infected patients and healthy controls in Salvador, Bahia, Brazil. Endothelial vasomotor function was evaluated by assessing brachial artery FMD. Forty-four HIV-infected individuals (33 ARV treated and 11 ART naive) were compared to 25 healthy controls matched for age and BMI. FMD % was significantly lower for the ART-experienced patients compared to the ART-naive patients and was also significantly different from controls (ART experienced 8.2 +/- 6.0% vs. 19.3 +/- 4.8% vs. 23.3 +/- 6.1%), respectively (p < 0.0001). The cholesterol, triglyceride, and ALT levels were significantly higher in the ART-experienced group compared to the ART-naive and control subjects (p < 0.028); however, linear regression analysis revealed a statistically significant association of endothelial dysfunction as a dependent variable only with ARV treatment in HIV-infected subjects (p = 0.03). The association of endothelial dysfunction with ARV therapy in HIV-infected patients was independent of protease inhibitor-containing regimens or dyslipidemia. This dysfunction may contribute to the risk for HIV-associated atherosclerosis.     

Relation of vasodilator response of the brachial artery to inflammatory markers in patients with coronary artery disease

Endothelial dysfunction of the coronary artery is closely related to elevated levels of systemic inflammatory markers and cardiovascular events in patients with coronary artery disease (CAD). We hypothesized that patients with CAD may have a higher risk of endothelial dysfunction of the peripheral artery than patients without evidence of CAD, and that endothelial dysfunction of the peripheral artery also may be related to elevated levels of inflammatory markers. Using high resolution ultrasound, we assessed the brachial vasodilator response to reactive hyperemia (endothelium-dependent) and sublingual nitroglycerin (endothelium-independent). As inflammatory markers, serum C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) levels, and lipid profiles were measured in patients with CAD (n = 30, 16 male and 14 female) and normal subjects without evidence of CAD (n = 45, 23 male and 22 female). Patients with CAD (Group II) showed a significantly reduced endothelium-dependent vasodilation as compared with normal subjects (Group I) (4.4 +/- 3.6 vs 7.4 +/- 6.1%, P < 0.05). However, endothelium-independent vasodilation was not significantly different between the two groups (7.7 +/- 7.1 vs 9.7 +/- 8.0%, P > 0.05). In Group II, CRP level was inversely related to endothelium-dependent vasodilation (r = -0.398, P = 0.029). In contrast, ESR level was not significantly associated to endothelium-dependent vasodilation (r = -0.113, P = 0.552). On multivariate analysis, CRP and low density lipoprotein cholesterol levels were significant independent predictors of a blunted endothelium-dependent vasodilation in Group II. Our study showed that elevated CRP level was associated with blunted endothelium-dependent vasodilation of the brachial artery in patients with CAD. Thus, identification of elevated CRP levels combined with demonstration of endothelial dysfunction of the brachial artery may have a possible clinical application for the detection of high risk CAD patients.     

Postprandial hypertriglyceridemia-induced endothelial dysfunction in healthy subjects is independent of lipid oxidation

BACKGROUND: To analyze the effects of postprandial hypertriglyceridemia with or without antioxidant supplementation-on endothelial function as related to lipid oxidation in healthy young subjects. METHODS AND RESULTS: Ten healthy male subjects (mean age: 26 years) were examined three times in fasting state (10 hours) following a high-fat meal, a low-fat meal, or a high-fat meal with additional antioxidant vitamin E (800 IU), respectively. Serum triglycerides significantly increased 2 and 4 hours after eating the high-fat meal with or without additional vitamin E. Endothelium-dependent, flow-mediated brachial artery vasodilations (FMD; percentage change in diameter) changed from 13.3+/-1.1% to 6.6+/-1.1% (p<0.05), 7.1+/-0.6% (p<0.05), or 13.2+/-0.8% at 2, 4, or 6 hours after eating a high-fat meal. However, there were no changes of FMD observed following either a low-fat meal or a high-fat meal with additional vitamin E. The flow-dependent vasodilation inversely correlated to postprandial hypertriglyceridemia (r=-0.54, p<0.05). Serum malondialdehydes (MDA; lipid oxidation products) did not significantly change following ingestion of any of the 3 types of meal. CONCLUSIONS: This study suggests that postprandial hypertriglyceridemia-induced endothelial dysfunction is not associated with lipid oxidation and that the protective effects of vitamin E on endothelial function may be due to some alternative, as of yet unknown, mechanism.     

冠心病患者血管内皮功能障碍与动脉弹性关系的研究

目的　探讨冠心病患者血管内皮功能障碍与动脉弹性的关系。方法　采用高分辨率血管超声法检测 30例冠心病患者与 30例正常对照组肱动脉血流介导的内皮依赖性血管舒张功能(FMD);应用动脉弹性功能检测仪测定受试者的大动脉弹性指数 (C1 )和小动脉弹性指数 (C2 )。结果　冠心病组血流介导的肱动脉舒张反应明显低于对照组[ (5 17±2 13)% 与 (11 10±4 36)%,P<0 05];冠心病组与正常对照组的C1 差异无统计学意义 [ ( 11 59±4 56 )ml/mmHg( 1mmHg=0 133kPa) ×10与 (12 11±3 82)ml/mmHg×10, P>0 05],但冠心病组的C2 明显低于正常对照组[ (4 20±1 80)ml/mmHg×100与 (6 26±2 36)ml/mmHg×100, P<0 05],冠心病组血流介导的肱动脉舒张反应与C2 呈正相关(r=0 53, P<0 05)。结论　冠心病患者肱动脉内皮依赖血管舒张功能受损和C2 降低,且两者之间呈正相关,提示C2 可作为一种评价血管内皮功能的新指标。     

Enhanced coronary calcification determined by electron beam CT is strongly related to endothelial dysfunction in patients with suspected coronary artery disease

BACKGROUND: Coronary artery calcification determined by electron beam CT (EBCT) is strongly associated with total plaque burden but is not related to systemic vascular inflammation.Aims: We sought to test the hypothesis that enhanced coronary artery calcification, a marker of atherosclerosis and plaque burden, was related to endothelial dysfunction in patients with suspected coronary artery disease (CAD). METHODS AND RESULTS: One hundred twenty-four subjects with suspected CAD were enrolled. Coronary artery calcification was detected by EBCT. A noninvasive method of brachial ultrasound was used to measure endothelium-dependent flow-mediated vasodilation (FMD) and endothelium-independent nitroglycerin-mediated vasodilation (NMD). Serum high-sensitivity C-reactive protein (hsCRP) and monocyte chemoattractant protein-1 (MCP-1) levels were also determined. Of the 124 patients, the calcium scores ranged from 0 to 4,394. All subjects were classified into three groups according to coronary calcium scores: group 1, score 0 (n = 26); group 2, scores 1 to 199 (n = 50); group 3, scores > or = 200 (n = 48). There was an inverse association between the degree of coronary artery calcification and the endothelium-dependent FMD in the three groups (6.9 +/- 0.6% vs 5.3 +/- 0.3% vs 3.7 +/- 0.3%, respectively; p < 0.001) but not the endothelium-independent NMD. Besides, no significant difference in serum levels of hsCRP and MCP-1 were found among the three groups. However, both the serum levels of hsCRP and MCP-1 were correlated significantly with endothelium-dependent FMD (r = - 0.211, p = 0.019; and r = - 0.188, p = 0.037, respectively). By multivariate analysis, enhanced coronary calcification was a strong independent predictor of endothelial dysfunction (p < 0.001). CONCLUSION: Enhanced coronary artery calcification strongly predicted endothelial dysfunction in patients with suspected CAD. Also, serum levels of hsCRP and MCP-1 were significantly correlated with endothelial function. These findings suggested that both calcium deposition and inflammation were involved in endothelial dysfunction.     

Oral snuff impairs endothelial function in healthy snuff users

AIMS: Oral snuff is a less dangerous drug and therefore a good substitute for cigarette smoking. The aim of this study was to determine whether oral moist snuff induces acute endothelial dysfunction. Previous studies have shown that endothelial dysfunction predicts cardiovascular morbidity. METHODS AND RESULTS: Twenty healthy middle-aged snuff users underwent ultrasound assessment of endothelial-dependent flow-mediated dilatation (FMD) of the brachial artery. FMD measurements were performed in duplicate at baseline and then 20 and 35 min after the administration of 1 g portion-bag-packed moist snuff or placebo. Ten of the subjects were examined twice according to a randomized cross-over procedure, once with snuff and once with placebo. All images were arbitrarily analysed off-line by a single blinded observer. FMD values declined significantly from 3.4 +/- 2.0% to 2.3 +/- 1.3% (P < 0.05) 35 min after the administration of 1 g oral moist snuff. Heart rate, systolic and diastolic blood pressure increased significantly (P < 0.05) after snuff administration. All parameters remained unchanged after placebo. CONCLUSIONS: Oral moist snuff significantly impaired FMD of the brachial artery. As endothelial dysfunction predicts cardiovascular morbidity, use of oral snuff should be discouraged.     

Measurement of the brachial-ankle pulse wave velocity and flow-mediated dilatation in young, healthy smokers.

The brachial-ankle pulse wave velocity (PWV) is a quick test which adequately estimates arterial stiffness. Because flow-mediated dilatation (FMD) of the brachial artery assesses an essential endothelial function, we tested the hypothesis that the brachial-ankle PWV could reflect the early stages of endothelial dysfunction caused by smoking in young, healthy subjects. Fifty-seven healthy subjects (13 females and 44 males; mean 29.9+/-5.6 years) were enrolled. Twenty-six of the subjects (30.4+/-5.7 years) were active smokers, with a mean cumulative nicotine consumption of 10.0+/-8.6 pack/years, and thus were assigned to the smoking group. Thirty-one subjects without a history of smoking (29.5+/-5.5 years) were assigned to the non-smoking group. The brachial-ankle PWV and arterial blood pressure were simultaneously measured using a recently established, non-invasive automatic device (model BP-203RPE; Nihon Colin, Tokyo, Japan). Endothelium-dependent FMD was induced by reactive hyperemia, while endothelium-independent vasodilation of the brachial artery was induced by administration of sublingual nitroglycerin spray. The FMD was lower in the smoking group than in the non-smoking group (p<0.05). There was no significant difference between the two groups with respect to the brachial-ankle PWV. In the non-smoking group, multiple stepwise regression analysis revealed that FMD was predicted by the systolic blood pressure (F=16.351). In the smoking group, statistical analysis revealed that FMD was independently predicted by either the brachial-ankle PWV (F=8.108) or the subject's age (F=4.381). Our results suggest that a reduction in FMD is closely associated with the early stages of endothelial dysfunction caused by cigarette smoking in young, healthy subjects, which is at least partly reflected by the PWV value.