Endothelial dysfunction and type of cigarette smoked: the impact of 'light' versus regular cigarette smoking

Acute cigarette smoking leads to temporary endothelial dysfunction, which is an early event in atherogenesis. Sufficient data concerning the effect of cigarettes with low tar and nicotine yield are lacking. Seventeen healthy individuals (nine women, eight men, aged 27.8 +/- 3.6 years) were subjected to evaluation of endothelial function by means of endothelium-dependent, flow-mediated dilatation (FMD) of the brachial artery, before, immediately after and 30, 60 and 90 min after smoking a regular cigarette (nicotine 0.9 mg, tar 12 mg) orthe corresponding 'light' cigarette (nicotine 0.6 mg, tar 8 mg). The following day, measurements were repeated after smoking the opposite kind of cigarette. Baseline FMD was 6.1 +/- 1.6% and 7.2 +/- 2.0% in the light and regular cigarette groups, respectively (p = NS). The overall effect of the regular cigarette over time on FMD compared with the light cigarette was significantly different (F = 3.039, p = 0.023). FMD was significantly depressed after smoking both types (light: F = 8.192, p < 0.001; regular: F = 16.698, p < 0.001). Immediately after smoking, FMD declined in both groups (light: 3.0 +/- 2.4% and regular: 1.6 +/- 3.2%, p < 0.001 and p < 0.001, respectively), and it remained significantly depressed in the regular cigarette group at 30 min (0.75+/-1.5%, p < 0.001) and 60 min (3.5 +/- 3.1%, p = 0.024), while in the light cigarette group FMD differences were abolished at 30, 60 and 90 min after smoking. In conclusion, acute smoking of both regular and light cigarettes leads to temporary vasomotor dysfunction; its duration is shorter after smoking a 'light' cigarette.     

Global impairment of brachial, carotid, and aortic vascular function in young smokers: direct quantification by high-resolution magnetic resonance imaging

OBJECTIVES: The purpose of this study was to assess vascular dysfunction in young smokers by high-resolution magnetic resonance imaging (MRI). BACKGROUND: Cigarette smoking is a well-known cause of endothelial dysfunction, reflected by impaired brachial artery reactivity to hyperemia. We hypothesized that smoking induces both peripheral endothelial dysfunction and altered function in central conduit arteries, and that these global changes in vascular function could be directly quantified in a single noninvasive examination using high-resolution MRI. METHODS: A total of 22 healthy young volunteers (mean age 31 +/- 2 years; 12 nonsmokers, 10 smokers: cumulative cigarette consumption 11.9 +/- 6.0 pack-years) underwent noninvasive high-resolution MRI to assess central vascular distensibility and pulse-wave velocity (PWV), and cross-sectional flow-mediated dilation (FMD) of the brachial artery. RESULTS: Brachial artery FMD was significantly reduced in smokers compared with nonsmokers (7.5 +/- 2.7% vs. 15.5 +/- 2.0%; p = 0.03), indicating impaired endothelium-dependant relaxation, whereas endothelium-independent responses to sublingual glyceroltrinitrate(400 mug) were identical in both groups. Impaired peripheral endothelial function in smokers was accompanied by striking decreases in central vascular distensibility in both the common carotid arteries (-45.7%; p = 0.02) and at multiple sites in the aorta (ascending aorta -26.9%, p = 0.04; thoracic descending aorta -25.0%, p = 0.01; abdominal descending aorta -25.5%, p = 0.02). Aortic arch PWV in smokers was increased by 19% (p = 0.02). CONCLUSIONS: Cigarette smoking induces global changes in both peripheral and central vascular function. Direct quantification of multiple parameters of vascular function using high-resolution MRI will provide powerful new approaches to the assessment of vascular disease pathogenesis, diagnosis, and treatment.     

冠心病患者肱—踝脉搏波速与血管内皮舒张功能相关

目的探讨冠心病患者肱—踝脉搏波速与内皮依赖性舒张功能的关系。方法选择98例冠心病患者和33例非冠心病对照者,采用高分辨率超声检测肱动脉血流介导的内皮依赖性血管舒张功能;自动脉搏波速度测定仪测定肱—踝脉搏波速。结果冠心病组肱动脉血流介导的内皮依赖性血管舒张功能明显低于对照组(5.4%±2.5%比11.1%±4.4%,P<0.01),冠心病组肱—踝脉搏波速明显高于对照组(1745.3±215.2cm/s比1495.3±202.3cm/s,P<0.01),两组硝酸甘油介导的内皮非依赖性血管舒张功能无明显差异;肱动脉血流介导的内皮依赖性血管舒张功能与肱—踝脉搏波速呈负相关(r=-0.70,P<0.001)。结论冠心病患者血管内皮功能受损和肱—踝脉搏波速增快,提示血管内皮舒张功能的受损伴随冠心病动脉硬化。     

Menopause is an independent factor augmenting the age-related increase in arterial stiffness in the early postmenopausal phase

The present study examined whether the menopause augments the age-related increase in brachial-ankle pulse-wave velocity (PWV). In total, 3149 women (ranging in age from 21 to 94 years) undergoing an annual health screening examination were enrolled in a cross-sectional study. Conventional atherosclerotic risk factors were examined, and the brachial-ankle PWV of each subject was determined. The relationship between age and the brachial-ankle PWV assumed the form of a quadratic curve, and the slope of the curve was relatively steeper after the menopause (brachial-ankle PWV = 0.17 x age2 - 0.58 x age + 812) than before (brachial-ankle PWV = 0.23 x age2 - 8.92 x age + 1058). A logistic regression analysis conducted for subjects between the ages of 45 and 56 years (mean age of menopause +/- 2 standard deviations) demonstrated that women who had experienced the menopause at least 6 years previously demonstrated a significant risk of belonging to the highest PWV tertile {adjusted odds ratio: 2.08 (95% confidential interval: 1.04-4.17)}, independent of age and other atherosclerotic risk factors (hypertension, hypercholesterolemia, diabetes mellitus, obesity, and smoking). Thus, this study suggested that the menopause augments the age-related increase in arterial stiffness during the early postmenopausal phase and that this augmentation is probably related, at least in part, to estrogen deficiency. The contribution of this menopause-related increase in arterial stiffness to the risk of cardiovascular disease in postmenopausal women should be further evaluated.     

Effects of vitamin E on chronic and acute endothelial dysfunction in smokers

OBJECTIVES: The aims of this study were to determine whether chronic or acute impairment of flow mediated vasodilation (FMD) in the brachial artery of smokers can be restored or preserved by the antioxidant vitamin E. BACKGROUND: Transient impairment of endothelial function after heavy cigarette smoking and chronic endothelial dysfunction in smokers result at least in part from increased oxidative stress. METHODS: We studied 22 healthy male smokers (mean +/- SD, 23 +/- 9 cigarettes per day) randomly assigned to receive either 600 IU vitamin E per day (n = 11, age 28 +/- 6 years) or placebo (n = 11, age 27 +/- 6 years) for four weeks and 11 age-matched healthy male nonsmokers. Flow mediated vasodilation and endothelium-independent, nitroglycerin-induced dilation were assessed in the brachial artery using high resolution ultrasound (7.5 MHz) at baseline and after therapy. Subjects stopped smoking 2 h before the ultrasound examinations. At the end of the treatment period, a third scan was obtained 20 min after smoking a cigarette (0.6 mg nicotine, 7 mg tar) to estimate transient impairment of FMD. RESULTS: Flow mediated vasodilation at baseline was abnormal in the vitamin E (5.3 +/- 3.8, p < 0.01) and in the placebo group (6.4 +/- 3.5, p < 0.05) compared with nonsmoking controls (11.6 +/- 4.7). Using a two-way repeated measures analysis of variance (ANOVA) to examine the effects of vitamin E on FMD, we found no effect for the grouping factor (p = 0.5834) in the ANOVA over time but a highly significant difference with respect to time (p = 0.0065). The interaction of the time factor and the grouping factor also proved to be significant (p = 0.0318). Flow mediated vasodilation values remained similar after treatment for four weeks in both groups but declined faster after smoking a cigarette in subjects taking placebo compared with those receiving vitamin E (p values from successive differences for the time/group factor: 0.0001/0.0017). The transient attenuation of FMD (calculated as the percent change in FMD) was related to the improvement of the antioxidant status, estimated as percent changes in thiobarbituric acid-reactive substances (r = -0.67, p = 0.0024). Nitroglycerin-induced dilation did not differ between study groups at baseline or after therapy. CONCLUSIONS: These results demonstrate that oral supplementation of vitamin E can attenuate transient impairment of endothelial function after heavy smoking due to an improvement of the oxidative status but cannot restore chronic endothelial dysfunction within four weeks in healthy male smokers.     

Smoking is associated with dose-related increase of intima-media thickness and endothelial dysfunction

Cigarette smoking is firmly established as a risk factor for atherosclerosis. However, the exact mechanism causing smoking-related damage to the arterial wall and its relation to the atherosclerotic process is not known. Also unknown is the time delay between the start of smoking and the sequence of functional and morphologic changes occurring in the arterial wall caused by smoking and their interrelationship. Therefore, the aim of this study was to evaluate the acute and chronic effects of smoking on endothelium-dependent (flow-mediated) dilation (FMD) of the peripheral arteries, the effects of dose and duration of chronic smoking on intima-media thickness (IMT) of the carotid arteries, and their interrelationship. The study encompassed two groups of smokers. In group A there were 40 subjects of both sexes, who smoked on average 17.6 +/- 6.5 cigarettes per day, for 5 to 15 years (mean 8.95 +/- 4.0 years), mean age 28.1 years. Group B consisted of 42 smokers of both sexes who smoked 21.15 +/- 8.2 cigarettes/day for more than 15 years (mean 21.15 +/- 3.4 years), mean age 39.5 years. The control group consisted of 40 healthy subjects without major risk factors of atherosclerosis, mean age 29.1 years. By means of high-resolution ultrasound the brachial artery diameter was measured at rest and during reactive hyperemia (after release of a forearm tourniquet) and the flow-mediated, endothelium-dependent dilation was calculated. The IMT of the carotid arteries was determined in all subjects by use of B-mode ultrasonography. Resting blood flow in the brachial arteries was significantly less in the smokers' groups than in controls (78.8 +/- 31.9 vs 134.9 +/- 45.0 mL/min, p<0.0001). This decrease was much more evident in female than in male smokers. Female smokers also had significantly smaller brachial artery diameter at rest. In smokers the FMD of the brachial artery was reduced (11 +/- 4% vs 7 +/- 4%, p<0.004) and the mean IMT was significantly greater than in controls (0.68 +/- 0.13 vs 0.59 +/- 0.04 mm, p<0.001). Impairments of FMD and IMT increase were related to the duration and to the number of cigarettes smoked. In all subjects IMT was significantly correlated with total and LDL cholesterol, fibrinogen, lipoprotein(a) concentration, body mass index, and age of the subjects, but multivariate analysis showed that only total dose smoked and fibrinogen concentration were independently related to IMT. The results of this study show that smoking is associated with dose-related impairment of FMD and increased IMT of the carotid arteries. Impairment of FMD occurs in smokers very early and is the earliest detectable event, preceding morphologic changes of the vessel wall. Some harmful effects of smoking on the vessel wall are gender related.     

The indexes of arterial structure and function in women with simple obesity: a preliminary study

Obesity is associated with an increased risk of cardiovascular disorders. The aim of the present study was to compare the indexes of arterial structure and function in women with simple obesity and healthy individuals. Twenty-two women with simple obesity (body mass index [BMI]: 33.6 +/- 2.9 kg/m(2), age: 29.7 +/- 6.2 years), and 34 healthy women were included in the study. Healthy subjects were divided into two subgroups according to their age (<35 and >45 years): Control A-16 young women (age <35 years, BMI: 24.0 +/- 3.0 kg/m(2)), and Control B-18 older women (age >45 years, BMI: 25.8 +/- 2.9 kg/m(2)). Noninvasive, high-resolution, vascular ultrasound was used to evaluate the endothelial-dependent vasodilatation: flow-mediated dilatation of brachial artery (FMD); the arterial structure: intima-media thickness (IMT) of common carotid artery (CCA); and the compliance parameters corresponding to structural changes in large arteries (PWV: pulse wave velocity; PP: pulse pressure; TAC: total arterial compliance; Ao C: aorta compliance, CCA C: CCA compliance, stiffness indexes). Endothelial-dependent vasodilatation as represented by FMD was comparable in the obese group (16.8% +/- 7.9%; median: 15.5%) and healthy subjects (Control A: 14.1% +/- 4.7%; median: 13.6%; Control B: 13.9% +/- 6.5%; median: 13.0%). The mean value of IMT was significantly increased (P < 0.05) in Control B group (0.67 +/- 0.07 mm) in comparison to both obese patients (0.58 +/- 0.09 mm) and Control A group (0.53 +/- 0.05 mm). The compliance parameters (PWV, AoC, CCA C, stiffness indexes) were impaired in obese patients and Control B patients as compared to Control A individuals. PWV and stiffness indexes were significantly increased, and the AoC, CCA C-diameter, CCA C-area were significantly decreased. Simple obesity constitutes an important risk factor accelerating arterial stiffness in women.     

Statin treatment improves cerebral more than systemic endothelial dysfunction in patients with arterial hypertension

BACKGROUND: The pleiotropic effects of statins on the endothelial function are well recognized. However, the effect of statins might not be equally pronounced in the cerebral and systemic circulation. We compared cerebral and systemic endothelial function by L-arginine cerebrovascular reactivity and flow-mediated dilatation (FMD), respectively, in patients with arterial hypertension (AH) and healthy controls before and after atorvastatin treatment. METHOD: L-arginine reactivity and FMD were measured in patients with AH (29 patients, aged 61.1 +/- 6.2 years) and 21 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-min intravenous infusion of L-arginine. FMD of the brachial artery after hyperemia was determined. The measurements were repeated after 3 months of treatment with atorvastatin. RESULTS: L-arginine reactivity and FMD were decreased in patients with AH (12.5 +/- 8.7%; 2.7 +/- 5.0 %) compared with controls (21.3 +/- 10.9%; 8.5 +/- 5.9%) (P < 0.01). After atorvastatin treatment, L-arginine reactivity and FMD improved in patients with AH (19.5 +/- 10.6%; 4.6 +/- 4.1%) compared with the controls (20.2 +/- 10.2%; 9.7 +/- 3.9%). The use of statin restored the cerebral circulation reactivity, while there was little change in the systemic circulation measured by FMD. CONCLUSION: The decreased L-arginine reactivity and FMD were found to improve after atorvastatin treatment in patients with AH, but the results suggest that statin therapy improved cerebral more than systemic endothelial function.     

CYBA C242T gene polymorphism and flow-mediated vasodilation in a population of young adults: the Cardiovascular Risk in Young Finns Study

OBJECTIVE: Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is a major source of the superoxide anion that contributes to decreased nitric oxide bioavailability in the vasculature. The C242T polymorphism of the CYBA gene that encodes p22phox, a component of NADPH oxidase, has been found to modulate superoxide production. We examined the relationship of the C242T polymorphism with endothelial-dependent brachial artery flow-mediated vasodilatation (FMD) in a population-based sample of young healthy adults. METHODS: FMD, defined as the increased percentage in brachial artery diameter after reactive hyperemia, was assessed by ultrasound and the C242T polymorphism using a 5' nuclease assay in 2058 subjects aged 24-39 years. RESULTS: The mean values of brachial artery FMD were 8.0 +/- 4.4% in all study subjects (n = 2058), and 7.8 +/- 4.4, 8.2 +/- 4.5, and 8.7 +/- 4.5% in subjects with the CC (n = 1362), CT (n = 616), and TT (n = 80) genotypes of the C242T CYBA polymorphism, respectively (P = 0.02 for trend). The association remained significant (P = 0.019) in multivariate analyses adjusted for age, sex, obesity indices, smoking habits, blood pressure, serum glucose, lipids, and C-reactive protein. The relationship between FMD and the C242T polymorphism was stronger (P = 0.004) in overweight subjects (body mass index > or = 25 kg/m, n = 895) and ever-smokers (P = 0.008, n = 1082), whereas no relationship was found in normal-weight subjects and non-smokers (P = 0.824 and P = 0.438, respectively). CONCLUSION: The C242T polymorphism of the CYBA gene seems to be related to endothelial function in a population-based sample of young healthy adults. Overweight and smoking status may modify this genetic effect.     

Comparison of central pulse pressure estimated from pulse wave propagation velocity and carotid pulse pressure measured by applantation tonometry

BACKGROUND: Pulse pressure (PP) corresponds to the difference between arterial systolic blood pressure and diastolic blood pressure. Central PP seems to be a stronger coronary risk marker than brachial PP. Central PP can be estimated by aortic PP measured non invasively by aplanation tonometry of the carotid artery. The aim of this study was to compare 2 methods of estimation of aortic PP: estimation from Pulse Wave Velocities (PWV) and by aplanation tonometry of the carotid artery. Estimation from PWV is based on the non uniform transmission of the PP i.e. the amplification of PP from the aorta to brachial artery, through arteries of increasing impedance. METHODS: One hundred and fifty one subjects were included, 111 hemodialysis patients and 40 subjects free of cardiovascular treatment or cardiovascular organ damage, recruited in a preventive medicine setting. Central PP was measured by aplanation tonometry of the carotid artery. The following formula was used for the relationship between PP and PWV in the two arterial segments considered for pulse wave travel (waterhammer formula): [formula: see text] Where measurement of brachial PP (PPBr) and PWV at aortic (PWVAo) and brachial (PWVBr) gives an estimation of aortic PP (PPAo estimated). Carotid-femoral PWV was used for PWVAo and carotid-radial PWV was used for PWVBr. The two methods were compared by t-test and according to Bland and Altman's method. RESULTS: In the hemodialysis group (73 males, 44 +/- 12 years old), brachial PP was 56 +/- 15 mm Hg and central PP as measured at the carotid level was 47 +/- 15 mmHg. In the healthy group (29 males, 46 +/- 11 years old), these values were 46 +/- 10 mmHg and 35 +/- 10 mmHg respectively. Compared to carotid artery aplanation tonometry, PPAo estimated was larger than central PP by 2.9 +/- 6.3 mmHg in hemodialysis patients and by 5.4 +/- 6.6 mmHg in the healthy group. The difference was significantly larger in healthy subjects than in hemodialysis patients (p = 0.031). CONCLUSION: The PWV estimated PP is larger than the central PP measured at the carotid level by aplanation tonometry. The difference is larger in cardiovascular event free subjects than in patients on hemodialysis.     

Relations of left ventricular mass and systolic function to endothelial function and coronary flow reserve in healthy, new discovered hypertensive subjects

Left ventricular hypertrophy (LVH) is prognostically relevant, associated with major cardiovascular risk factors and with atherosclerosis. However, whether LVH is independently associated with impaired coronary flow reserve (CFR) and with endothelial dysfunction is disputed. We assessed the relationship of LV mass and systolic function to CFR and endothelial function in new discovered never treated subjects with essential arterial hypertension, but without coronary artery disease or microalbuminuria. LVH, ejection fraction (EF) and stress-corrected midwall shortening (MWS, a measure of myocardial contractility) were assessed by echocardiography. CFR was assessed by single-photon emission computed tomography and dipyridamole infusion. Endothelial function was evaluated by assessing 1-min postischaemic flow-mediated dilatation of the brachial artery (FMD); nitroglycerine-mediated dilatation (NMD) of the same brachial artery was used as measure of nonendothelium-dependent vasodilatation. In approximately 1 year, we enrolled 21 subjects who met stringent inclusion criteria (47+/-10 years old, 26.6+/-2.8 kg/m2, 78% men). Five patients showed LVH. Multivariate analyses showed a significant negative correlation of LV mass index with FMD (beta=-0.61, P<0.05) but not with NMD, neither with CFR. Stress-corrected MWS showed independent correlation with CFR (beta=0.51, P<0.05). Thus, in clinically healthy, new discovered hypertensive subjects, never treated and mostly in the early stage of arterial hypertension, LVH can be associated with endothelial dysfunction while maximal dipyridamole- dependent CFR may be preserved; nevertheless, a cardiac phenotype presenting with tendency to impaired myocardial contractility, assessed by stress-corrected MWS, showed association with lower CFR in the early stage of arterial hypertension.     

Myocardial perfusion reserve and peripheral endothelial function in patients with idiopathic dilated cardiomyopathy

The aim of this study was to assess the relation between peripheral endothelial function and myocardial perfusion reserve in patients with mild heart failure due to idiopathic dilated cardiomyopathy (IDC). Myocardial perfusion and brachial artery flow mediated dilation (FMD) were measured in 20 clinically stable patients with IDC (New York Heart Association classes I to III, ejection fraction 35 +/- 9%) and 13 apparently healthy subjects who were matched for age and lipid profile. Resting and hyperemic (dipyridamole; 0.56 mg/kg/min) perfusion were measured using oxygen-15-labeled water and positron emission tomography (PET). Perfusion reserve was calculated as the ratio of hyperemic to resting perfusion. FMD was assessed by measuring the change in brachial artery diameter in response to reactive hyperemia. Patients with IDC had lower hyperemic perfusion (1.73 +/- 0.83 vs 3.01 +/- 1.20 ml/min/g, p <0.001) and perfusion reserve (2.01 +/- 0.91 vs 3.08 +/- 1.35, p <0.01) compared with healthy subjects. Brachial artery FMD, however, was not different from that of the healthy subjects. Furthermore, neither hyperemic perfusion nor perfusion reserve was correlated with FMD in the patients with IDC, whereas the healthy subjects demonstrated a positive correlation between FMD and perfusion reserve (r = 0.57; p = 0.04). Thus, abnormal myocardial perfusion characterizes patients with IDC. Myocardial perfusion reserve and peripheral endothelial function do not parallel each other in patients with IDC.     

Comparison of arterial assessments in low and high vascular disease risk groups

BACKGROUND: An increasing number of arterial function assessments are available, including small and large arterial elasticity (SAE/C2, LAE/C1), endothelial function as measured by flow mediated dilation (FMD), carotid intima-medial thickness (IMT), ankle brachial index (ABI), pulse pressure (PP), and pulse wave velocity (PWV). We have consecutively performed these measures in subjects with low and high vascular disease risks to assess the interrelationships. METHODS AND RESULTS: Twenty healthy subjects (HS) and 20 older subjects with type 2 diabetes mellitus (DM) were studied with all techniques at a single sitting by a single operator. In HS, C2 correlated with FMD (R = 0.577, P = .008), PWV (R = 0.522, P = .046), and ABI (R = 0.463, P = .04). There was no significant correlation of C1 and FMD or blood pressure (BP) measurements. In DM, C2 correlated with FMD (R = 0.443, P = .05), systolic BP (R = -0.553, P = .01), PP (R = -0.601, P = .005), and systemic vascular resistance (R = -0.577, P = .008). There was no significant correlation between anthropometric measures and arterial function measures in either group. The IMT was not correlated with any measure of arterial function in either group. CONCLUSIONS: C2 assessed by pulse wave analysis correlated with endothelial function measured by FMD in young apparently healthy subjects and older subjects with type 2 diabetes. Systolic BP and PP correlated with C2 and FMD in older diabetic subjects but not healthy subjects. The interrelationships between arterial function measures are different in high and low risk populations. This variability needs to be considered when applying these techniques to individuals in different populations.     

阻塞性睡眠呼吸暂停低通气综合征患者动脉粥样硬化无创检测指标分析

目的检测血流介导的血管扩张(FMD)、脉搏波传导速度(PWV)和颈动脉内膜中层厚度(CIMT),探讨阻塞性睡眠呼吸暂停低通气综合征(OSAHS)与动脉粥样硬化之间的关系。方法对76例OSAHS患者(OSAHS组)及76例年龄、性别、体重指数与之相匹配患者(对照组)进行FMD、PWV和CIMT检测,对两组间FMD、PWV和CIMT值进行比较,对OSAHS组睡眠呼吸暂停低通气指数(AHI)与FMD、PWV和CIMT之间关系进行相关性分析。结果OSAHS组PWV[(1720±247)cm/s]、CIMT[(1.10±0.34)mm]显著高于对照组[(1469±172)cm/s、(0.80±0.18)mm],FMD[(5.8±1.7)%]显著低于对照组[(8.9±1.4)%,P均<0.01];比较两组中所有伴高血压者,OSAHS组PWV、CIMT[(1850±244)cm/s、(1.24±0.35)mm]仍显著高于对照组[(1655±161)cm/s、(0.99±0.18)mm,P=0.001、0.003],FMD[(5.2±1.7)%]显著低于对照组[(7.5±1.1)%,P<0.01];OSAHS组AHI值与PWV、CIMT值呈正相关(r=0.883、0.698,P均<0.01),与FMD值呈负相关(r=-0.711,P<0.01)。结论OSAHS患者存在更为明显的内皮功能障碍及动脉粥样硬化,且与OSAHS严重程度有关。     

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.     

Treatment of essential arterial hypertension with enalapril does not result in normalization of endothelial dysfunction of the conduit arteries

It is assumed that endothelial dysfunction due to arterial hypertension could be improved or even normalized by antihypertensive treatment. The present study was designed to explore that assumption in patients with essential hypertension treated with an angiotensin-converting enzyme (ACE) inhibitor-enalapril. Twenty-eight patients (mean age: 55.1 years) who fulfilled the following criteria were included: essential arterial hypertension present for more than 2 years, monotherapy with enalapril for at least 1 year, adequate treatment (blood pressure in the last year <140/90 mm Hg) and absence of other factors (smoking, hypercholesterolemia, diabetes, obesity), which could importantly influence endothelial function. The flow-mediated (endothelium-dependent) dilation (FMD) of the brachial artery was assessed by high-resolution ultrasound and compared with that of 22 age-matched healthy normotensive controls. The patients and controls did not differ in regard to body mass index, lipids, and plasma glucose and insulin; there were no smokers. FMD of the brachial artery was significantly decreased in patients in comparison to controls (7.9% vs 13.5%, p<0.01). FMD in patients was inversely correlated with the duration of hypertension (r = -0.52, p<0.01) and with both systolic (r = -0.72, p<0.01) and diastolic (r = -0.43, p<0.05) blood pressure (measured after temporary withdrawal of treatment). This study showed that the adequate control of blood pressure achieved with enalapril is not followed by normalization of endothelial function, measured by FMD of the brachial artery.     

Endothelial function in patients with obstructive sleep apnea syndrome but without hypertension

BACKGROUND: Obstructive sleep apnea syndrome (OSAS) influences endothelial function and causes hypertension. OBJECTIVES: Our aim was to evaluate the role of endothelial dysfunction in the pathogenesis of hypertension in OSAS. METHODS: Twenty-three patients with OSAS but without hypertension and 15 healthy normotensive subjects were investigated. The presence or absence of OSAS was evaluated with a sleep study. Endothelial function was investigated with brachial artery ultrasound examination. RESULTS: Baseline characteristics were equivalent between the two groups. Minimal oxygen saturation and apnea-hypopnea indexes in the OSAS and control groups were 62.9 +/- 16.5 versus 94.9 +/- 1.1% (p < 0.0001) and 53.1 +/- 20.3 versus 3.8 +/- 0.9 (p < 0.0001), respectively. There was not statistically significant difference between basal brachial artery diameters measured in the morning and in the evening in all groups. Flow-mediated dilation (FMD) values measured in the morning were lower than those measured in the evening in both OSAS patients and the control group: FMD of OSAS patients was 6.04 +/- 3.18% in the morning and 10.38 +/- 4.23% in the evening hours (p = 0.001), and FMD of control subjects was 10.9 +/- 2.6% in the morning and 13.9 +/- 2.32 in the evening hours (p = 0.002). Differences in FMD values measured both in the morning and evening hours in OSAS patients were lower compared with those in control subjects (p < 0.0001 in the morning hours and p = 0.003 in the evening hours). CONCLUSIONS: We detected a prominent diurnal deterioration in endothelial function in normotensive OSAS patients compared with healthy subjects. This deterioration may occur due to ongoing hypoxemia during the night and it may be a possible cause of hypertension and atherosclerotic cardiovascular diseases in patients with OSAS.     

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.     

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.     

Impaired endothelial function in hypertensive elderly patients evaluated by high resolution ultrasonography.

BACKGROUND: Multiple investigations both in experimental models and in middle-aged patients with essential hypertension have demonstrated impaired endothelium-dependent vasodilation. OBJECTIVE: To determine whether hypertension exerts an additional negative effect on endothelial function of large arteries in hypertensive elderly patients who may already be affected by endothelial dysfunction due to aging. PATIENTS AND METHODS: Thirteen elderly patients with hypertension (69 9 years of age [mean SD]) were compared with 13 matched healthy elderly subjects (72 6 years of age). High resolution vascular ultrasound was used to measure brachial artery responses to reactive hyperemia (with increased flow causing endothelium-dependent dilation) and to sublingual nitroglycerine (causing endothelium-independent dilation). RESULTS: Flow-mediated diameter (FMD) was significantly impaired in the hypertensive elderly group (6.7 3.3% versus 13.3 3.8% in the control group, P<0.05). No significant difference could be found in nitroglycerine-induced dilation between the elderly control group (12.1 4.9%) and the hypertensive elderly (10.2 6.8%). On simple linear analysis, FMD was inversely correlated with age (r=-0.60, P=0. 03) in the healthy elderly group. FMD in the hypertensive elderly was inversely related to age (r=-0.41, P=0.04) and mean blood pressure (r=-0.67, P=0.01). CONCLUSIONS: This study showed decreased FMD with aging even in the healthy elderly, with a further decline in hypertensive elderly compared with healthy elderly subjects. This impairment of FMD in the hypertensive elderly group was related to age and mean blood pressure, indicating that aging and hypertension may impair endothelial function in the brachial artery of elderly patients with hypertension.