Impaired coronary microvascular endothelial function in men with metabolic syndrome

AIM: To assess coronary endothelial function of conduit and resistance vessels in patients with metabolic syndrome (MS).METHODS: Seventy-eight men (mean age, 57 years) with chest pain and angiographically normal coronary arteries were included in the study. Patients with coronary spastic angina were excluded. Changes in coronary artery diameter and coronary blood flow (CBF) in response to acetylcholine (ACh) were determined using quantitative coronary angiography and Doppler velocity measurements. Coronary flow reserve was calculated as the ratio of coronary blood velocity after adenosine triphosphate infusion relative to baseline values. Patients were divided into two groups based on the presence or absence of MS.RESULTS: There were 24 patients in the MS group (31%). The increase in CBF in response to ACh infusion was impaired in the MS group (P < 0.0001) compared to the non-MS group, whereas changes in coronary artery diameter in response to ACh infusion did not differ between the two groups. Multivariate regression analysis revealed that MS was a significant factor associated with the lesser change in CBF induced by ACh infusion at 30 μg/min (P < 0.0001, r² = 0.46).CONCLUSION: Coronary endothelial dysfunction was present at the level of resistance vessels but not conduit vessels in the MS patients included in our study.     

Coronary endothelium-dependent and independent vasomotor responses in patients with hypertrophic cardiomyopathy.

It is well known that coronary flow reserve (CFR) is decreased in patients with hypertrophic cardiomyopathy (HCM), but it is unclear whether coronary endothelial function is impaired. Coronary endothelial function and CFR in the coronary macro- and microcirculation was evaluated in 14 patients with HCM and 11 control subjects. Acetylcholine (ACh), bradykinin (BK) and papaverine were infused into the left coronary artery. Coronary cross-sectional area was determined by quantitative coronary angiography and coronary blood flow (CBF) was determined by the product of the coronary cross-sectional area and CBF velocity measured by an intracoronary Doppler guidewire. Acetylcholine at 100 microg induced diffuse coronary spasms of the left anterior descending coronary arteries in 3 of the patients with HCM. The changes in the diameter of the left anterior descending coronary artery and the increases in CBF induced by BK (0.2, 0.6, and 2.0 microg/min) did not differ between the 2 groups. CFR was lower in the HCM group than in the control group (p<0.01). Moreover, the ratio of BK-induced CBF increase to papaverine-induced CBF increase was comparable between the 2 groups. Endothelium-dependent vasodilation of the epicardial and resistance coronary arteries induced by BK was preserved despite the decreased CFR in patients with HCM.     

培垛普利对冠心病患者经皮冠状动脉介入术后肱动脉内皮功能障碍的影响

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

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.     

Reduction of peripheral flow reserve impairs endothelial function in conduit arteries of patients with essential hypertension

BACKGROUND: A diminished flow reserve in resistance vessels is a hallmark of hypertensive microvascular disease. Hypertension is associated with structural alterations in the microcirculation and a reduced endothelium-dependent dilation in conduit arteries. Both have been demonstrated to predict future cardiovascular events. OBJECTIVE: We hypothesized that a reduced peripheral flow reserve impairs endothelial function in upstream conduit arteries in patients with arterial hypertension. DESIGN: In 43 hypertensive patients (HT) and 38 normotensive controls (NT) endothelial function of the brachial artery was assessed by measurement of flow-mediated dilatation (FMD), using high-resolution ultrasound. Peripheral flow reserve (FR) was determined via measurements of forearm blood flow at rest and during increments of reactive hyperaemia, using venous occlusion plethysmography. RESULTS: FMD was markedly impaired in HT (3.6 +/- 0.3%) as compared with NT (10.2 +/- 0.3%), whereas maximum brachial artery diameter following endothelium-independent dilatation was similar in both groups. In hypertensive patients FR was significantly reduced (HT, 3.2 versus NT, 6.0) during reactive hyperaemia after 5 min of ischaemia. FR was associated with FMD (r = 0.68, P < 0.01). Multiple stepwise regression analysis identified FR as a strong independent variable determining the extent of FMD (r2 = 0.46, P < 0.01). In HT the dose-response curve of FMD upon stepwise increases of FR was shifted significantly to the right. Normalization of FR improved FMD in HT by more than 60%. CONCLUSIONS: In essential hypertension a reduced FR contributes to the endothelial dysfunction of upstream conduit arteries. These findings may have therapeutic and prognostic implications in patients with arterial hypertension.     

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

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

Baroreflex sensitivity normalization after cardiac resynchronization therapy

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

Comparable prognostic value of vasodilator response to acetylcholine in brachial and coronary arteries for predicting long-term cardiovascular events in suspected coronary artery disease.

BACKGROUND: Vasodilator response to acetylcholine (ACh) (ie, endothelium-dependent dilation) is impaired in the peripheral and coronary circulation of patients with coronary risk factors and coronary artery disease (CAD). There is a close relationship of vasodilator response to ACh in both the coronary artery (CA) and the brachial artery (BA), but the comparative prognostic importance of these responses has not been fully investigated in relatively low-risk suspected CAD. METHODS AND RESULTS: The flow responses of both the CA and BA were measured in 70 patients with suspected CAD, excluding patients with triple-vessel disease and known peripheral or cerebrovascular disorders. A Doppler guidewire was placed into a major branch of the CA and a proximal portion of the left BA. ACh was infused at 10(-8), 10(-7) and 10(-6) mol/L for 3 min into the CA and at 7.5, 15, and 30 mug/min for 5 min into BA. The flow response was obtained by multiplying the average peak velocity by the cross-sectional area from quantitative angiography. Vasodilator response to ACh was assessed by the ratio of ACh-induced flow/baseline flow, expressed as coronary blood flow index (CBFI) or brachial blood flow index (BBFI). There were 39 CAD patients (61 +/- 8 years old) and 31 normal coronary patients (NL, 58 +/- 11 years old) who were followed up for 53 +/- 17 months. Eleven patients had coronary events (CE) during this period: 1 case of nonfatal myocardial infarction and 10 cases of unstable angina. A strong correlation between CBFI and BBFI was observed at middle-and high-doses of ACh (r=0.72, p<0.0001, 15 microg/min vs 10(-7) mol/L; r=0.76, p<0.0001, 30 microg/min vs 10(-6) mol/L). Kaplan-Meier analysis, using the best cut-off values obtained from receiver-operating characteristic curves for CE, revealed that both CBFI and CAFI were significant predictors for CE. CONCLUSIONS: The BA vasodilator response to optimal ACh dosage can be used as a surrogate prognostic predictor for coronary endothelial function tests in patients with suspected CAD.     

冠心病血管内皮功能、颈动脉硬化与冠脉病变的关系

目的：观察冠心病（CAD）患者内皮依赖性舒张功能及颈动脉粥样硬化的状况及与冠状动脉病变的相关性。方法：选经冠状动脉造影确诊为CAD的患者106例（观察组），冠状动脉造影证实无冠状动脉狭窄的健康者40例（正常对照组），采用二维超声检测肱动脉内皮依赖性和非依赖性舒张功能及颈动脉粥样硬化病变。颈动脉粥样硬化斑块积分采用Sutton法，并与冠状动脉病变程度进行对比分析。结果：CAD组内皮依赖性血管舒缩功能（FMD）比正常对照组明显降低（P〈0．01），内皮非依赖性血管舒缩功能与正常对照组比较无显著性差异（P〉0．05）；CAD组颈动脉内膜中层厚度（IMT），斑块积分显著高于正常对照组（P〈0．01）。FMD与冠脉病变程度呈负相关（r=-0．651，P〈0．001），颈动脉IMI及斑块积分与冠脉病变程度呈正相关（r=0．871，0．702，P〈0．001）。结论：内皮细胞功能障碍和颈动脉粥样硬化与冠状动脉粥样硬化的病变相平行。     

Large and small artery endothelial function in patients with essential hypertension--effect of ACE inhibition and beta-blockade

Hypertension has been associated with changes in endothelial function in both large muscular arteries and small resistance arteries. We evaluated the relationship between blood flow velocity and dilatation of the brachial artery following transient forearm ischemia and acetylcholine-induced relaxation in subcutaneous small arteries and the influence of antihypertensive therapy on both in patients with essential hypertension. Thirty-one previously untreated hypertensive patients were randomized in a double-blind fashion to treatment with either the angiotensin-converting enzyme (ACE) inhibitor perindopril or the beta-blocker atenolol and compared with 17 healthy normotensive controls. Before and after 1 year of treatment, while still on active medication, flow-mediated dilatation (FMD) was measured in the brachial artery using ultrasound while relaxation to acetylcholine in small arteries was tested in vitro in a myograph. FMD correlated inversely to resting brachial artery diameter (r = -0.38, p<0.05). FMD corrected for resting diameter (FMD(corr)) was lower in patients (3.0+/-0.2%) compared with controls (4.2+/-0.3%, p<0.01). In both patients and controls, FMD(corr) was related to flow velocity in a non-linear way with FMD(corr) reaching a maximum despite increasing flow velocities, and in the patients, FMD(corr) was only reduced at high flow velocities. Furthermore, patients had a reduced acetylcholine-induced relaxation in small arteries (p = 0.04). Perindopril and atenolol reduced blood pressure to similar levels and both drugs improved FMD(corr) to a similar degree without any effects on relaxation to acetylcholine in small arteries. The present study demonstrates the role of correcting for differences in baseline diameter during measurements of FMD and a non-linear relationship between flow velocity and FMD in the brachial artery. Furthermore, the results suggest different effects of antihypertensive treatment on endothelial function in large and small arteries.     

Noninvasive low-frequency ultrasound energy causes vasodilation in humans.

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

Vascular function correlates with risk factors for cardiovascular disease in a healthy population of 35-year-old subjects

OBJECTIVE: To investigate whether, in a healthy, randomly selected population of 35-year-old men and women, there is a relation between vascular function and conventional risk factors for cardiovascular disease such as gender, smoking, elevated blood-lipids, high blood pressure and heredity for cardiovascular disease, and to blood glucose. DESIGN: Basal brachial artery diameter was measured. Endothelial function was measured as flow mediated dilation (FMD) in response to reactive hyperaemia. The nonendothelial dependent dilation was measured after sublingual nitro-glycerine (NTG). SETTING: A research centre of general medicine and a university hospital. SUBJECTS: One hundred men and 100 women all 35 years old, were invited by letter. Sixty-six of the 92 men (72%) living in the community and 74 of the 88 women (84%) participated. RESULTS: Gender had the largest influence on FMD and NTG induced arterial dilation, probably reflecting the larger vessel diameters in the men as FMD and NTG induced dilation is inversely related to basal vessel size (r = -0.55, P < 0.001 and r = -0.40, P < 0.001). In women basal vessel diameter was positively correlated to blood glucose (r = 0.35, P = 0.009) and BMI (r = 0.34, P = 0.012) and negatively correlated to HDL cholesterol (r = -0.43, P = 0.001). FMD and NTG induced arterial dilation correlated with a combined risk factor score (r = -0.32, P = 0.019 and r = -0.31, P = 0.024). The men with the highest risk factor scores had larger vessel size and higher blood flow at rest compared to men without risk factors (4.8 +/- 0.6 mm, 240 +/- 84 mL min-1 and 4.0 +/- 0.8 mm, 139 +/- 72 mL min-1, respectively, P = 0.014 and P = 0.016). FMD or NTG induced dilation did not correlate to any of the risk factors in men. CONCLUSIONS: There are correlations between vascular reactivity and risk factors for IHD in women and correlations between vessel diameter and risk factors for IHD in both men and women already in a healthy population 35-year-old subjects. Further studies are needed to determine if the vessel diameter in itself, in a healthy population, is a sign of attenuated endothelial function.     

The effect of rapid decreases of blood pressure by different mechanisms on coronary flow and flow reserve in normal coronary arteries

BACKGROUND: Changes in mean blood pressure (MBP) alter coronary blood flow (CBF). We evaluated the acute effects of three hypotensive medications on CBF parameters in angiographically normal coronary arteries. METHODS: We performed CBF measurements using the Doppler wire at rest and during hyperemia produced by intracoronary adenosine (18 microg) as follows: 1) in the normal left circumflex coronary artery in 20 patients with coronary artery disease (measurements were performed without drugs, and after intravenous infusion of nitroprusside [0.5 to 2 microg/kg/min] and nitroglycerin [10 to 90 microg/min]; drugs were titrated to decrease MBP 20% to 25% below the control values, and heart rate was held constant using right atrial pacing); and 2) in the normal left anterior descending coronary artery in 19 patients without coronary artery disease (measurements were performed before and after intravenous clonidine infusion [150 microg in 5 min]; time-averaged peak velocity [APV], CBF, and coronary flow reserve [CFR] were measured). RESULTS: Similar decreases in MBP were obtained in the two patient groups. Lumen diameter at the site of Doppler measurements increased after all medications (P <.005), whereas CBF did not change significantly. The CFR decreased after nitroprusside (1.79 +/- 0.48 v 2.54 +/- 0.45, P=.000), did not change significantly after nitroglycerin (2.74 +/- 0.43 v 2.54 +/- 0.45, P =.097), and increased after clonidine (3.12 +/- 0.70 v 2.76 +/- 0.75, P =.006). CONCLUSIONS: In normal coronary arteries the infusion of three hypotensive medications to produce the same decreases in MBP is associated with different effects on CFR (increase with clonidine, decrease with nitroprusside, and no change with nitroglycerin).     

Effect of alcohol consumption on endothelial function in men with coronary artery disease

An inverse relationship between moderate alcohol consumption and coronary artery disease (CAD) has been observed in several epidemiologic studies. Whether improvement of endothelial function is involved in this beneficial effect is unknown. We investigated endothelial function of the brachial artery in 108 men with CAD, 54 of whom consumed alcohol on at least 1 day per week. Brachial artery diameter responses to hyperemic flow (FMD) and to administration of nitroglycerin (NTG) spray were measured using high- resolution ultrasonography. Coronary risk factors and hyperuricemia were present more frequently among drinkers, who also had higher concentrations of triglyceride and apolipoproteins C2, C3, and E. FMD was greater in drinkers (P<0.0001), while NTG-induced dilation was not. Multiple regression analysis showed alcohol consumption to be one of the factors favorably influencing FMD. These findings suggest that alcohol consumption may improve endothelial function in men with CAD.     

Effect of Long-Term Angiotensin II Type I Receptor Antagonism on Peripheral and Coronary Vasomotion

Angiotensin II, via AT1 receptors plays a key role in endothelial dysfunction and therefore, in atherogenesis. In order to assess whether long-term blockade of these receptors improve peripheral and coronary endothelial function, 13 patients were treated by candesartan cilexetil (AT2B, 16 mg/d in 10 patients and 8 mg in 3). Flow-mediated dilation (FMD, measured with ultra-sound technique) in the brachial artery and cold pressor testing (CPT)-induced changes in myocardial blood flow (MBF, measured with positron emission tomography) were assessed before and after a 6 month treatment period. AT2B did not alter FMD: 5.0 +/- 1.2% vs. 6.4 +/- 0.9% after treatment. MBF increased significantly during CPT before and after AT2B. Although AT2B did not significantly modify heart rate and blood pressure, MBF normalized to the rate pressure product (MBF/RPP x 10000) was significantly higher and this change remained significant during CPT: it increased from 0.94 +/- 0.05 ml/g/min to 1.14 +/- 0.09 ml/g/min after AT2B (P < .05) and did not decrease during CPT (1.12 +/- 0.08 ml/g/min). Moreover, these AT2B-induced changes in normalized MBF were significantly correlated with the changes in FMD (r = 0.66, P < 0.05). Thus, long-term AT2B improves coronary vasomotion. Although no significant alteration in peripheral conduit endothelial function has been observed, treatment-induced FMD changes seem to be a predictor of coronary circulation improvement.     

Effect of regular exercise on coronary endothelial function in patients with recent myocardial infarction.

Exercise training improves the endothelial function of arteries in skeletal muscle, but few studies have examined its clinical effect on human coronary endothelial function. Non-infarct-related coronary arteries in 41 patients with a recent myocardial infarction who underwent successful percutaneous transluminal coronary angioplasty were studied. Patients were divided into 2 groups: regular exercisers (n=24, 17 males, mean age: 58 years), and non-exercisers (n=17, 12 males, mean age: 58 years). Acetylcholine (ACh) was infused into the non-infarct-related coronary artery and its diameter was measured by quantitative angiography at baseline and at 6 months after angioplasty. ACh, given in doses of 1, 3, 10, 30 microg/min, increased the coronary artery diameter in a dose-dependent manner in both groups. The mean percent change in the diameter at the site of stenosis change (%DS) was less in the regular exercisers than in the non-exercisers (11%+/-12 vs 41%+/-36, p<0.05). Multivariate analysis showed that regular exercise was the only significant determinant of improvement in endothelial function (p=0.01). These findings suggest that regular exercise improves endothelial function in the coronary arteries following myocardial infarction.     

Plasma level of oxidized low-density lipoprotein is an independent determinant of coronary macrovasomotor and microvasomotor responses induced by bradykinin

OBJECTIVES: We examined the relationship between coronary endothelium-dependent vasodilation in response to bradykinin (BK) and plasma levels of oxidized low-density lipoprotein (oxLDL) in subjects with normal coronary arteries. BACKGROUND: It is unclear whether the plasma oxLDL level is a determinant of coronary endothelial function. Bradykinin plays an important role in regulating resting coronary tone and flow-mediated coronary vasomotion. METHODS: Coronary blood flow (CBF) in the left anterior descending (LAD) coronary artery was assessed by quantitative angiography and a Doppler flow wire in 94 consecutive subjects with normal coronary arteries. The plasma oxLDL level was measured by enzyme-linked immunosorbent assay using DLH3R, a specific antibody against oxLDL. RESULTS: Plasma levels of oxLDL in diabetic subjects (n = 13) were higher than those in non-diabetic subjects (n = 81). Plasma levels of oxLDL correlated with body mass index (BMI). Bradykinin at doses of 0.2, 0.6, and 2.0 microg/min caused dose-dependent increases in diameter and CBF in the LAD coronary artery. By a univariate analysis, oxLDL levels significantly correlated with epicardial (r = -0.30, p < 0.0001) and resistant (r = -0.36, p = 0.003) coronary vasodilator responses to BK at 2.0 microg/min, whereas total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides were not associated with these coronary responses. In a stepwise multivariate analysis, oxLDL levels were significantly correlated with epicardial and resistant coronary vasomotor responses to BK, independent of age, gender, smoking status, other lipid levels, BMI, hypertension, and diabetes. CONCLUSIONS: The plasma level of oxLDL is an appropriate surrogate for assessing coronary endothelial-dependent vasomotor function as estimated by responses to BK compared with conventional risk factors for atherosclerosis.     

Antiplasmin correlates to arterial reactivity in a healthy population of 35-year-old men and women

OBJECTIVE: To study whether haemostasis function variables correlate with endothelial function and other vasomotion characteristics of the brachial artery in a randomly selected healthy population of 35-year-old men and women. DESIGN: Endothelial function was measured as flow mediated dilatation (FMD) of the brachial artery during reactive hyperaemia and the nonendothelial dependent dilatation after sublingual nitroglycerin (NTG) was administered. Haemostasis and fibrinolysis function were estimated by analysis of von Willebrand factor, plasminogen activator inhibitor-1, antiplasmin and fibrinogen. SETTING: A general medicine research centre and a university hospital. SUBJECTS: Randomly chosen men (n = 53) and women (n = 56). RESULTS: Univariate correlation analysis showed significant correlations between haemostasis factors, conventional risk factors for cardiovascular disease and indices of vasomotion of the brachial artery. In multivariate analysis, with haemostasis variables and conventional risk factors included, antiplasmin was the strongest explanatory variable for FMD. When antiplasmin was removed from the analysis, the r-value dropped from 0.46 to 0.35. Antiplasmin also correlated with NTG-induced dilatation (positively) and brachial diameter at rest (negatively), albeit less consistently. CONCLUSIONS: Antiplasmin correlates significantly and independently to FMD, reflecting endothelial function, and also to brachial artery diameter at rest and nitroglycerin-induced dilatation. In multivariate analysis these correlations of antiplasmin to arterial characteristics were stronger than for 'conventional' risk factors, such as smoking, blood pressure and serum cholesterol.     

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.     

Positive influence of aspirin on coronary endothelial function: Importance of the dose

AIM: To investigate the effects of different doses of aspirin on coronary endothelial function.METHODS: The study included 139 Japanese subjects (mean age, 60 years; 53 women) with angiographically normal coronary arteries. Patients were distributed into Group I (n = 63), who was administered aspirin and Group II (n = 76), the control, who were not administered aspirin. Group I was further divided into Group Ia (n = 50, low-dose aspirin, 100 mg) and Group Ib (n = 13, high-dose aspirin, 500 mg). After a routine coronary angiography, acetylcholine (ACh; 3 and 30 μg/min successively) and nitroglycerin (NTG) were infused into the left coronary ostium over 2 min. The change in the diameter of the coronary artery in response to each drug was expressed as the percentage change from baseline values.RESULTS: The patient characteristics did not differ between the two groups. The change in coronary diameter in response to ACh was greater in Group I than in Group II (P = 0.0043), although the NTG-induced coronary vasodilation was similar between groups. ACh-induced dilation was greater in Group Ia than in Group Ib (P = 0.0231). Multivariate regression analysis showed that a low-dose of aspirin (P = 0.0004) was one of the factors associated with ACh-induced dilation at 30 μg/min.CONCLUSION: In subjects with angiographically normal coronary arteries, aspirin only had a positive influence on coronary endothelial function at the low dose of 100 mg. This improvement of coronary endothelial function may be involved in the preventive effect of aspirin against future coronary events.