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.     

Endothelial function in obstructive sleep apnea and response to treatment

Impaired endothelium-dependent vascular relaxation is a prognostic marker of atherosclerosis and cardiovascular disease. We evaluated endothelium-dependent flow-mediated dilation (FMD) and endothelium-independent nitroglycerin (NTG)-induced dilation of the brachial artery with Doppler ultrasound in 28 men with obstructive sleep apnea (OSA) and 12 men without OSA. Subjects with OSA (apnea-hypopnea index; mean +/- SD, 46.0 +/- 14.5) had lower FMD compared with subjects without OSA (5.3 +/- 1.7% vs. 8.3 +/- 1.0%, p < 0.001), and major determinants of FMD were the apnea-hypopnea index and age. There was no significant difference in NTG-induced dilation. Subjects with OSA were randomized to nasal continuous positive airway pressure (nCPAP) or observation for 4 weeks. Subjects on nCPAP had significant increase in FMD, whereas those on observation had no change (4.4% vs. -0.8%, difference of 5.2%, p < 0.001). Neither group showed significant change in NTG-induced vasodilation. Eight subjects who used nCPAP for over 3 months were reassessed on withdrawing treatment for 1 week. On nCPAP withdrawal, FMD became lower than during treatment (p = 0.02) and were similar to baseline values. Our findings demonstrated that men with moderate/severe OSA have endothelial dysfunction and treatment with nCPAP could reverse the dysfunction; the effect, however, was dependent on ongoing use.     

Endothelial dysfunction and low grade chronic inflammation in subclinical hypothyroidism due to autoimmune thyroiditis

The relationship between subclinical hypothyroidism (SH) and cardiovascular disease has been one of the most popular topics recently. There is still some controversy concerning its cardiovascular impact and management protocols. Our study aims to investigate the presence of the well known preceding clinical situations of atherosclerosis like endothelial dysfunction and inflammation in subclinical hypothyroidism. Thirty-seven patients with subclinical hypothyroidism (29 women, 8 men) and 23 healthy volunteers (19 women, 4 men) were recruited for the study. Endothelial dysfunction was measured by examining brachial artery responses to endothelium-dependent (flow mediated dilation, FMD) and endothelium-independent stimuli (sublingual nitroglycerin (NTG)). Serum TNF-alpha, interleukin-6, and hs-CRP were measured. The estimate of insulin resistance by HOMA score was calculated with the formula: fasting serum insulin (μIU/mL) x fasting plasma glucose (μM/L) / 22.5. There were no significant differences in age, body mass index, waist circumference, HOMA scores. There was a statistically significant difference in endothelium-dependent (FMD) and endothelium-independent vascular responses (NTG) between the patients with subclinical hypothyroidism and the normal healthy controls. The groups were well matched for baseline brachial artery diameter. The TSH and LDL, IL-6, TNF-alpha and hs-CRP levels in the patient group were significantly higher than those in control group. A positive correlation was found only between endothelium-dependent vasodilation and TNF-alpha, hs-CRP and IL-6, TSH, total cholesterol, LDL and triglycerides. Endothelium-independent vascular response was not correlated with any of the metabolic or hormonal parameters. Neither of the groups were insulin resistant and there was not any difference either in fasting insulin or in glucose levels. We found endothelial dysfunction in subclinical hypothyroidism group. Endothelium-dependent (FMD) and endothelium-independent vascular responses (NTG) were lower in patient group. Our findings suggest that there is endothelial dysfunction and low grade chronic inflammation in SH due to autoimmune thyroiditis. There are several contributing factors which can cause endothelial dysfunction in SH such as changes in lipid profile, hyperhomocysteinemia. According to our results low grade chronic inflammation may be one of these factors.     

老年周围动脉闭塞性疾病内皮和非内皮依赖性舒张功能的无创研究

目的　探讨老年周围动脉闭塞性疾病 (peripheralarterialocclusivedisease,PAOD)内皮依赖性舒张功能 ,即血流介导的血管扩张功能 (flow mediateddilation ,FMD)和硝酸甘油介导的非内皮依赖性舒张功能 (nitroglycerin mediateddi lation,NMD)状况及其相关因素。方法　采用超声多普勒检测 33例已确诊为PAOD的老年患者肱动脉FMD及NMD ,并分别与 40例健康老年人及 30例具有心血管危险因素的老年非PAOD患者进行对照研究。结果　老年PAOD患者FMD及NMD均显著低于对照组 ;肱动脉基础内径、收缩压、低密度脂蛋白胆固醇与FMD呈负相关 ;FMD与NMD呈正相关 ,肱动脉基础内径与NMD呈负相关。结论　老年PAOD患者FMD及NMD均受损 ;肱动脉基础内径、收缩压、低密度脂蛋白胆固醇可能是FMD独立的预测因子 ;而FMD及肱动脉基础内径与NMD密切相关。     

冠心病合并2型糖尿病患者的血清AGEs与内皮依赖性血管舒张功能关系探讨

目的　探讨冠心病合并 2型糖尿病 (2 - DM)患者内皮依赖性血管舒张功能与血清糖基化终产物(AGEs)水平变化及二者的关系。方法　选择 6 0例冠心病合并 2 - DM患者为治疗组 ,在冠心病综合治疗的基础上给予胰岛素或其他降糖药物控制血糖 ;另选 6 0例查体健康者为对照组。检测两组血清 AGEs、NO水平 ,采用 Jud-kins法进行选择性冠状动脉造影 ,高分辨超声技术检测肱动脉的血管舒张功能。结果　治疗组治疗前后血清AGEs、NO水平及内皮依赖性血管舒张功能均与对照组有明显差异 (P <0 .0 5 ,<0 .0 1) ,且治疗组治疗前后上述指标亦均有明显差异 (P <0 .0 1)。内皮依赖性血管舒张功能减弱程度与血清 AGEs水平呈负相关 (r =- 0 .39,P <0 .0 1) ,血清 NO水平与血清 AGEs水平呈负相关 (r=- 0 .31,P <0 .0 1)。结论　冠心病合并 2 - DM患者内皮依赖性血管舒张功能明显减弱 ,血清 AGEs水平明显升高 ,可能是 AGEs削弱了其内皮依赖性血管舒张功能。长期良好的血糖控制可降低冠心病合并 2 - DM患者血清 AGEs水平 ,增加血液中 NO水平 ,改善其内皮依赖性血管舒张功能     

Measurement of flow-mediated vasodilation of the brachial artery: a comparison of measurements in the seated and supine positions.

BACKGROUND: Measurement of flow-mediated vasodilation (FMD) is used to assess endothelial function in humans and according to the guidelines, subjects must remain supine during the study. However, measurement of FMD while seated would be more comfortable and convenient for patients, so the purpose of this study was to determine the effect of the patient's position on FMD results. METHODS AND RESULTS: High-resolution ultrasonography, a linear array transducer (13 MHz) and an arm-holding device were used to measure arterial diameter in response to reactive hyperemia (FMD, cuff inflated to 50 mmHg above systolic blood pressure for 5 min) and in response to sublingual nitroglycerine (NTG, 75 microg) in 31 subjects, which included those with cardiovascular diseases. There was no significant difference between basal or peak hyperemic blood flow in the seated or supine position. Basal brachial artery diameter, FMD and vascular response to NTG were similar in both positions (basal diameter: 3.8+/-0.4 vs 3.9+/-0.4 mm, FMD: 7.3+/-4.3% vs 7.2+/-4.5%, NTG: 13.1+/-5.1% vs 12.8+/-5.6%). CONCLUSIONS: The findings suggest that measurement of FMD in the seated position is as useful as measuring it in the supine position for assessing endothelial function. This flexibility of position is better for patients and physicians, and should lead to more widespread measurement of FMD.     

Improved endothelium dependent vasodilation in endurance athletes and its relation with ACE I/D polymorphism.

BACKGROUND: Aerobic exercise enhances endothelium-dependent vasodilation in healthy individuals. It is thought that exercise increases nitric oxide (NO) production and decreases NO inactivation, leading to an increase in NO bioavailability. Angiotensin II and NO have important roles in maintaining vascular tone. There are polymorphisms of the angiotensin converting enzyme (ACE) gene and the presence of the deletion (D) allele has been associated with higher concentrations of circulating and tissue ACE. In this study, the relationship between endothelial function and ACE gene polymorphisms was investigated in athletes and sedentary subjects. METHODS AND RESULTS: The study group comprised 56 endurance athletes and 46 sedentary subjects who underwent brachial artery ultrasonographic examination. ACE insertion (I) and D allele frequencies were analyzed in all patients. Baseline brachial artery diameter and resting blood flow were similar in athletes and controls (p > 0.05). The flow-mediated dilation (FMD) was 8.48+/-3.65% in athletes and 5.16+/-2.5% in controls (p = 0.0001). FMD was significantly different between ACE genotypes in the athletes (p < 0.0001): it was higher in ACE II (10.5+/-1.6%) subjects than in the DI (8.4+/-2.3%) or DD (7+/-1.2%) subgroups. CONCLUSION: Regular isotonic exercise can improve endothelium-dependent vasodilation especially in those with the ACE II genotype.     

Volume Elastic Modulus,Vascular Function,and Vascular Structure in Patients with Cardiovascular Risk Factors

Aims: Volume elastic modulus (V _E ), an index of arterial elasticity, and arterial diameter of the brachial artery can be automatically measured by a newly developed oscillometric device. We investigated the associations of V _E with flow-mediated vasodilation (FMD), an index of endothelium-dependent vasodilation, nitroglycerine-induced vasodilation (NID), an index of endothelium-independent vasodilation, and intima-media thickness (IMT) of the brachial artery and association of oscillometrically measured brachial artery diameter with ultrasonographically measured brachial artery diameter in patients with cardiovascular risk factors. Methods: Oscillometric measurements of V _E and brachial artery diameter and ultrasound measurements of brachial artery diameter, FMD, NID, and IMT of the brachial artery were performed in 50 patients with cardiovascular risk factors. Results: The mean values were 2.1±0.4 mmHg/% for V _E , 0.31±0.05 mm for brachial IMT, 4.48±0.70 mm for oscillometric brachial artery diameter, and 4.30±0.55 mm for ultrasound brachial artery diameter. V _E significantly correlated with brachial IMT (r=0.51, P ＜0.001), whereas there was no significant correlation of V _E with FMD (r=-0.08, P =0.58) or NID (r=0.07, P =0.61). Multivariate analysis revealed that V _E was significantly associated with brachial IMT (β=0.33, P =0.04). Oscillometric brachial artery diameter significantly correlated with ultrasound brachial artery diameter (r=0.79, P ＜0.001). The Bland-Altman plot showed good agreement between oscillometric brachial artery diameter and ultrasound brachial artery diameter (mean difference, -0.17 mm; limits of agreement, -1.03 mm to 0.69 mm). Conclusions: In patients with cardiovascular risk factors, V _E may represent atherosclerotic structural alterations of the vascular wall but not vascular function. The accuracy of oscillometric measurement of brachial artery diameter is acceptable.     

Aortic stiffness, flow-mediated dilatation and carotid intima-media thickness in obstructive sleep apnea: non-invasive indicators of atherosclerosis

BACKGROUND AND OBJECTIVE: Obstructive sleep apnea (OSA) has a critical association with cardiovascular mortality and morbidity. Carotid intima-media thickness (IMT), flow-mediated dilatation (FMD) and aortic stiffness are early signs of atherosclerosis. The presence of subclinical atherosclerosis was assessed in OSA patients using these parameters. METHODS: 40 patients with OSA showing an apnea-hypopnea index (AHI) > or =5 (mean age 51.3 +/- 9 years, 32 males) and 24 controls (AHI < 5, mean age 51.9 +/- 5.2 years, 19 males) were enrolled in the study. In all subjects, polysomnographic examination and recordings were performed during sleep. IMT of the carotid artery, endothelium-dependent/-independent vasodilation of the brachial artery and aortic elastic parameters were investigated using high-resolution Doppler echocardiography. RESULTS: The demographic data of the patients with OSA and controls were not significantly different. Subjects with OSA demonstrated higher values of aortic stiffness (7.1 +/- 1.88 vs. 6.42 +/- 1.56, respectively) and IMT (0.85 +/- 0.13 vs. 0.63 +/- 0.11 mm, p = 0.0001, respectively) but lower distensibility (9.47 +/- 1.33 vs. 11.8 +/- 3.36 cm(2)/dyn/10(6)) and FMD (4.57 +/- 1.3 vs. 6.34 +/- 0.83%, p = 0.0001, respectively) than the controls. The respiratory disturbance index correlated positively with aortic stiffness and IMT and negatively with distensibility and FMD. CONCLUSION: We observed blunted endothelium-dependent dilatation, increased carotid IMT and aortic stiffness in patients with OSA compared with matched control subjects. This is evident in the absence of other diseases, suggesting that OSA is an independent cause of atherosclerosis. These simple and non-invasive methods help to detect subclinical atherosclerosis in OSA.     

Effect of anger provocation on endothelium-dependent and -independent vasodilation

Anger is an independent predictor of coronary heart disease events, although the mechanisms for this relation are unclear. The effects of an anger-provoking interview compared with a neutral interview on endothelium-dependent and -independent vasodilation assessed by brachial artery ultrasound were examined in 14 healthy subjects without coronary heart disease risk factors. The anger provocation condition, but not the neutral condition, caused a significant impairment in endothelium-dependent vasodilation at 90 minutes compared with baseline (p = 0.004) and 30 minutes (p = 0.013). Similarly, endothelium-independent vasodilation was significantly impaired at 90 minutes after the angry interview compared with baseline (p = 0.003) and 30 minutes (p = 0.001). The decreases in endothelium-dependent and -independent vasodilation were greater after the anger-provoking interview than after the neutral interview, especially between 30 and 90 minutes. In conclusion, preliminary results suggest that an episode of anger is associated with a dysregulation in endothelium-dependent and -independent pathways, suggesting that these mechanisms might contribute to the link between anger and coronary heart disease events.     

The prognostic importance of endothelial dysfunction and carotid atheroma burden in patients with coronary artery disease

OBJECTIVES: The goal of this study was to determine the relative prognostic importance of noninvasive measures of endothelial function and atheroma burden in patients with coronary artery disease (CAD). BACKGROUND: Direct measurement of atherosclerosis by carotid ultrasound and endothelial function assessment by brachial artery flow-mediated dilation (FMD) have both been shown to predict vascular events. The combined prognostic utility of carotid ultrasound and FMD relative to traditional risk markers and cardiovascular fitness has not been evaluated. METHODS: A total of 152 patients with CAD underwent metabolic testing, exercise stress tests, carotid ultrasound, and endothelial function measurements. RESULTS: Patients were followed for 34 +/- 10 months during which 22 vascular events occurred. Peak FMD (p = 0.012) and FMD/nitroglycerin-mediated dilation (NMD) ratio (p = 0.008) were lower in subjects with events. Univariate analysis with Cox proportional hazards modeling identified plaque area (p = 0.0047), total area (p = 0.0085), peak FMD (p = 0.01), FMD/NMD ratio (p = 0.008), stress test workload (p = 0.027), long-acting nitroglycerin (NTG) (p = 0.0071), and calcium blockers (p = 0.0057) as predictors of adverse events. Multivariate analysis showed that FMD/NMD ratio (p < 0.0001), carotid plaque area (p = 0.06), and NTG (p = 0.005) were independent predictors. Based on median values, subjects were divided into high and low "plaque burden" groups and into high and low FMD/NMD subgroups. Patients with high FMD/NMD had low event rates irrespective of the degree of carotid atheroma. Patients with low FMD/NMD and high "plaque burden" had the highest event rate (p < 0.05). CONCLUSIONS: The structural and functional status of the vasculature are independent predictors of coronary events as shown by noninvasive measurement of endothelial function and carotid atheroma burden in patients with CAD. Preserved endothelial function attenuates the risk of future events associated with a high plaque burden.     

Effect of a short-term primary prevention program on endothelium-dependent vasodilation in adults at risk for atherosclerosis

BACKGROUND: Endothelium-dependent vasodilation is impaired in asymptomatic subjects with risk factors for atherosclerosis. PURPOSE: To determine whether a three-month integrative primary prevention program can improve endothelial function in asymptomatic subjects with risk factors for atherosclerosis. PATIENTS AND METHODS: Twenty-two asymptomatic middle-aged men and women (13 men and nine women) aged 55 +/- 7 years with sedentary lifestyle and dyslipidemia (low density lipoprotein [LDL] level greater than 3.4 mmol/L) underwent an exercise test, determination of fasting blood lipid levels and noninvasive measurement of brachial artery reactivity before and three months after the beginning of a prevention program. The program consisted of exercise training (three times per week) and National Cholesterol Education Program step 1 diet in all subjects. A smoking cessation program was offered when applicable (six patients). Brachial artery diameter was measured by using high resolution ultrasound at rest, during reactive hyperemia (flow-mediated dilation [FMD], which is endothelium-dependent) and after sublingual nitroglycerin (NTG) (endothelium-independent vasodilation). RESULTS: After three months, peak oxygen uptake increased significantly from 25.4 +/- 4.9 to 27.5 +/- 4.8 mL/kg/min (P < 0.005), and LDL level decreased significantly from 4.48 +/- 0.92 to 4.00 +/- 0.83 mmol/L (P < 0.005). FMD and NTG responses assessed as percentage of diameter change from baseline, however, did not change (FMD 5.4 +/- 4.3% before and 5.1 +/- 3.9% at three months, not significant; NTG 8.4 +/- 3.8% before and 7.4 +/- 4.5% at three months, not significant). CONCLUSIONS: Short-term application of the currently recommended lifestyle intervention in adults with coronary risk factors did not improve vascular endothelial function. Longer and more aggressive programs may be needed to improve vascular function in subjects with risk factors for atherosclerosis.     

Impact of acute caffeine ingestion on endothelial function in subjects with and without coronary artery disease

Although coffee is a widely used, pharmacologically active beverage, its impact on the cardiovascular system is controversial. To explore the effect of acute caffeine ingestion on brachial artery flow-mediated dilation (FMD) in subjects without coronary artery disease (CAD; controls) and patients with CAD, we prospectively assessed brachial artery FMD in 40 controls and 40 age- and gender-matched patients with documented stable CAD on 2 separate mornings 1 week to 2 weeks apart. After overnight fasting, discontinuation of all medications for ≥12 hours, and absence of caffeine for >48 hours, participants received capsules with caffeine 200 mg or placebo. One hour after drug ingestion, participants underwent brachial artery FMD and nitroglycerin-mediated dilation (NTG) using high-resolution ultrasound. As expected, patients with CAD were more often diabetic, hypertensive, obese, dyslipidemic, and smoked more than controls (p <0.01 for all comparisons). Aspirin, Clopidogrel, angiotensin-converting enzyme inhibitors, β blockers, and statins were significantly more common in patients with CAD than in controls (p <0.01 for all comparisons). At baseline, FMD, but not NTG, was significantly lower in patients with CAD compared to controls. Acute caffeine ingestion significantly increased FMD (patients with CAD 5.6 ± 5.0% vs 14.6 ± 5.0%, controls 8.4 ± 2.9% vs 18.6 ± 6.8%, p <0.001 for all comparisons) but not NTG (patients with CAD 13.0 ± 5.2% vs 13.8 ± 6.1%, controls 12.9 ± 3.9% vs 13.9 ± 5.8%, p = NS for all comparisons) and significantly decreased high-sensitivity C-reactive protein (patients with CAD 2.6 ± 1.4 vs 1.4 ± 1.2 mg/L, controls 3.4 ± 3.0 vs 1.2 ± 1.0 mg/L, p <0.001 for all comparisons) in the 2 groups compared to placebo. In conclusion, acute caffeine ingestion significantly improved endothelial function assessed by brachial artery FMD in subjects with and without CAD and was associated with lower plasma markers of inflammation.     

Relationship between carotid artery intima-media thickness and brachial artery flow-mediated dilation in middle-aged healthy men

OBJECTIVES: We aimed to determine the relationship between carotid intima-media thickness (IMT) and brachial artery flow-mediated dilation (FMD) in healthy middle-age men. BACKGROUND: Carotid IMT and brachial artery FMD are frequently used as surrogate measures of subclinical atherosclerosis. Whereas carotid IMT identifies early structural abnormalities, brachial artery FMD, considered a bioassay of endothelial function, measures functional vascular integrity. The relationship between carotid IMT and brachial artery FMD has not been well studied. METHODS: We measured traditional risk factors, carotid IMT, and brachial artery FMD in 1,578 middle-aged men without known cardiovascular disease and analyzed the relationship between carotid IMT and brachial FMD. RESULTS: Carotid IMT correlated with age, systolic blood pressure, body mass index, fasting glucose, total and low-density lipoprotein (LDL) cholesterol, and with the overall Framingham risk score (p < 0.001 for all), whereas impaired brachial artery FMD correlated with systolic and diastolic blood pressure (p < 0.01). No relationship was observed between carotid IMT and brachial artery FMD for the entire cohort (r = -0.006, p = 0.82) and in subgroups defined by traditional risk factors or by quintiles of carotid IMT and brachial FMD. CONCLUSIONS: In middle-aged healthy men, there is no significant correlation between carotid IMT and brachial artery FMD. This finding suggests that these are unique, independent surrogates that measure different aspects and stages of early atherosclerosis. Further studies are needed to define their role in clinical research and in cardiovascular risk assessment.     

Impaired brachial artery endothelial function is not predicted by elevated triglycerides

OBJECTIVES

The purpose of this study was to determine if patients with modest hyperlipidemia, and no other risk factors for coronary artery disease (CAD), have impaired endothelium-dependent (ED) vasoactivity.

BACKGROUND

Hypercholesterolemia impairs ED vasodilation, but the impact of elevated triglycerides on endothelial function is not as well established.

METHODS

High-resolution ultrasound was used to determine flow-mediated dilation (FMD) in the brachial artery (BA) after a 5-min arterial occlusion (endothelium-dependent stimulus) and nitroglycerin-induced dilation (endothelium-independent stimulus). We studied 40 healthy controls (Group 1), 38 patients with elevated low-density lipoprotein (LDL) cholesterol (Group 2) and 35 patients with elevated triglycerides (Group 3). Patients were excluded if they had known CAD or other risk factors for CAD, or if they were receiving lipid-lowering or vasoactive medications.

RESULTS

Control patients (Group 1) had normal LDL cholesterol (2.6 ± 0.8 mmol/liter) and triglyceride levels (1.0 ± 0.5 mmol/liter) compared with Group 2 (5.2 ± 1.2 mmol/liter, 1.8 ± 0.6 mmol/liter) and Group 3 (3.5 ± 0.9 mmol/liter, 4.2 ± 2.5 mmol/liter) subjects (p < 0.001). Baseline BA diameters were the same across the three groups. There was no significant attenuation of flow-mediated vasodilation (FMD) in either of the hyperlipidemic groups (Group 1: 10.9 ± 5.0% vs. Group 2: 8.6 ± 6.1% vs. Group 3: 9.4 ± 3.9%; p = 0.14). However, nitroglycerin-induced vasodilation was mildly reduced (Group 1: 21.0 ± 5.0% vs. 16.9 ± 7.6% vs. 17.3 ± 7.7%; p = 0.01). By multivariate analysis, after controlling for baseline diameters, only the ratio of LDL/high-density lipoprotein predicted a minor impairment in FMD.

CONCLUSIONS

In patients free from other cardiac risk factors, modest elevations of triglycerides or LDL cholesterol do not significantly attenuate BA endothelial-dependent vasodilation. Synergism with other cardiac risk factors may be required to significantly impair endothelial function in these patients.     

Impaired endothelium-dependent vasodilation in the brachial artery in variant angina pectoris and the effect of intravenous administration of vitamin C

Endothelial dysfunction in the coronary artery contributes to the pathogenesis of variant angina, and endothelial dysfunction in variant angina may be associated with increased oxidant stress in the systemic arteries. We investigated whether endothelial dysfunction exists in the peripheral artery in patients with variant angina, and also examined the effect of vitamin C, an antioxidant, on endothelium-dependent vasodilation. Using high-resolution ultrasound, both the flow-mediated vasodilation (FMD, endothelium-dependent vasodilation) and sublingual nitroglycerin-induced vasodilation (NTG-D, endothelium-independent vasodilation) in the brachial artery were measured in 28 patients with variant angina and 24 control subjects who had normal coronary arteries. FMD was significantly impaired in patients with variant angina compared with control subjects (1.8 +/- 2.2% vs 6.4 +/- 4.9%, p <0.001). FMD and NTG-D before and after intravenous administration of either vitamin C or placebo were measured in 17 patients with variant angina. FMD significantly improved after the administration of vitamin C (from 2.2 +/- 2.4% to 4.5 +/- 1.6%, p <0.01), but not after administration of the placebo (from 2.0 +/- 2.6% to 1.7 +/- 1.9%). The improved FMD due to vitamin C in patients with variant angina, however, was not significantly different from that in the control subjects. NTG-D was not significantly different between patients with variant angina and control subjects (14.0 +/- 7.8% vs 13.6 +/- 5.0%) and it was also not affected by vitamin C. In conclusion: (1) FMD in the brachial artery is impaired in patients with variant angina, and (2) the acute administration of the antioxidant, vitamin C, was observed to reverse this endothelial dysfunction. These findings support the theory that the systemic inactivation of nitric oxide due to oxidative stress might exist in patients with variant angina.     

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.     

冠心病患者动脉弹性与血管舒张功能受损的关系

目的探讨冠心病患者动脉弹性和内皮与非内皮依赖性血管舒张功能的关系。方法采用高分辨率血管超声法检测30例冠心病患者(冠心病组)与健康体检非冠心病者30例(对照组)肱动脉血流介导的内皮依赖性血管舒张功能及硝酸甘油介导的非内皮依赖性血管舒张功能;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)。结果冠心病组与对照组的C1差异无显著性意义,但冠心病组的C2明显低于对照组,冠心病组内皮依赖性血管舒张功能与非内皮依赖性血管舒张功能均明显低于对照组;冠心病组C2不仅与内皮依赖性血管舒张功能呈正相关,且同非内皮依赖性血管舒张功能呈正相关。结论冠心病组C2降低,C2降低不仅同血管内皮功能的受损相关,而且也受非内皮因素的影响,提示C2反映总体血管舒张功能受损的程度。     

Vasodilation in resistance arteries is related to the apolipoprotein B/A1 ratio in the elderly: the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study

BACKGROUND: Recent studies have shown the apolipoprotein B to apolipoprotein A1 ratio (apoB/A1) to be superior to LDL-cholesterol measurements to predict cardiovascular events. The present study aims to relate apoB/A1 to endothelium-dependent vasodilation, an early marker of atherosclerosis, in the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS) study. METHODS AND RESULTS: In this population-based study, 1016 subjects aged 70 years were evaluated by the invasive forearm technique with acetylcholine (EDV), brachial artery ultrasound to assess flow-mediated vasodilation (FMD) and pulse wave analysis with a beta-2 receptor agonist challenge, terbutaline. EDV and the pulse wave response, but not FMD, were related to apoB/A1 levels (r=-0.11, p=0.0038 for EDV, r=-0.16, p<0.0001 for the pulse wave analysis and r=0.01, p=0.65 for FMD). Neither LDL-cholesterol, nor non-HDL-cholesterol, was significantly related to the measurements of endothelium-dependent vasodilation. Also endothelium-independent vasodilation (EIDV) evaluated by the invasive forearm technique with sodium nitroprusside was related to apoB/A1 levels (r=-0.12, p<0.0016). CONCLUSION: The apoB/A1 levels, but not LDL-cholesterol, were inversely related to endothelium-dependent vasodilation evaluated by EDV and pulse wave analysis, but not by FMD. Also EIDV showed the same pattern, suggesting a general deterioration in vasoreactivity mainly in resistance arteries in elderly subjects with high apoB/A1 levels.     

Noninvasive assessment of impaired endothelial dysfunction in mucocutaneous Behçet’s disease

Noninvasive assessment of endothelial dysfunction (ED) and diagnosing the early vascular development of atherosclerosis in active mucocutaneous Behçet’s disease. Twenty-nine active BD patients (study group) without any obstructive vascular involvement were compared with twenty-nine healthy controls (control group) in terms of ED utilizing endothelium-dependent dilation as well as endothelium-independent dilation (FMD), which was assessed by measuring changes in brachial artery diameter following sublingual glyceril trinitrate (400 μg Nitrolingual spray). All patients underwent a complete transthoracic echocardiographic and tissue Doppler study. A standard form was utilized for the documentation of the presence or absence of the known risk factors for atherosclerotic vascular disease. Statistical analysis was performed by utilizing SPSS version 11. There was no difference between patients and controls in terms of echocardiographic and tissue Doppler parameters as well as baseline brachial artery diameters. Flow-mediated dilation showed 38% impairment in study group compared with control (P < 0.05). Endothelium-independent NTG dilatation did not differ in both groups. Ultrasonography is an easily applicable noninvasive method for following BD patients for the risk of ED, which may preclude to atherosclerosis, save time and cost-effective.