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.     

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.     

Non-invasive evaluation of endothelial function in hypertensive elderly patients

Impaired endothelium-dependent vasomotion is a diffuse disease process resulting in abnormal regulation of blood vessel tone and loss of several atheroprotective effects of the normal endothelium. The aim of the present study was to investigate the effects of aging and hypertension on endothelial function. Sixty-six geriatric subjects with ages over 60 (48 hypertensive and 18 healthy) and 40 middle-aged subjects (16 hypertensive and 24 healthy) were included in the study. Systemic vascular endothelial function was evaluated through measuring brachial arterial vasodilation, a physiologic answer to reactive hyperemia occured with increased blood flow in the vessel after transient ischemia (flow-mediated dilation, FMD%), and with carotid artery intima-media thickness (IMT) measurement, using high-resolution ultrasonography. Endothelial independent vasodilation was also measured after administration of sublingual isosorbide dinitrate (isosorbide dinitrate mediated dilation, IDNMD%). FMD% was significantly decreased in elderly and/or hypertensive (HT) patients (geriatric HT: 9.5 +/- 4.7%, geriatric non-HT: 12.7 +/- 5.5%, middle-aged HT: 12.9 +/- 4.3% and middle-aged non-HT: 18.9 +/- 8.1%) (geriatric HT versus geriatric non-HT (P = 0.02), geriatric HT versus middle-aged HT (P = 0.01), geriatric non-HT versus middle-aged non-HT (P = 0.008)). Both FMD% and IDNMD% were inversely correlated with age, baseline vessel diameter and carotid artery intima-media thickness. FMD% was also inversely correlated with diastolic blood pressure. No correlation was found between FMD% and systolic blood pressure, serum cholesterol and triglyceride levels. Endothelium dependent (EDD) and independent dilatation of large arteries decreased with aging even in the healthy elderly, and FMD further declined in HT elderly patients, indicating that age and hypertension independently impair endothelial function. Positive correlations with age and hypertension, and significant inverse correlation with FMD, makes carotid artery IMT a possible indicator of endothelial function.     

Left ventricular hypertrophy is associated with reduced vasodilatory capacity in the brachial artery in patients with longstanding hypertension. A LIFE substudy

BACKGROUND: Left ventricular (LV) hypertrophy has been found to be associated with endothelial dysfunction in untreated patients with mild, uncomplicated hypertension. Whether similar relations exist in patients with longstanding hypertension and target organ damage remain to be elucidated. METHODS: In 40 unmedicated, hypertensive patients with electrocardiographic LV hypertrophy we measured 24-h ambulatory blood pressure (n = 37), LV mass index by echocardiography (LVMI(echo)) and magnetic resonance imaging (LVMI(MRI), n = 31), flow-mediated (FMD) and nitroglycerin-induced dilatation (NID) in the brachial artery by ultrasound, acetylcholine- (AIR) and nitroprusside-induced relaxation (NIR) in isolated resistance arteries by wire-myography. RESULTS: LVMI(MRI) correlated negatively to NID (r = -0.60, p < 0.001, n = 30) and to FMD (r = -0.53, p < 0.01, n = 31), but were not significantly correlated to maximal AIR nor NIR. NID (r = -0.53, p < 0.001, n = 36), FMD (r = -0.43, p < 0.01, n = 37), LVMI(MRI) (r = 0.60, p < 0.001, n = 29) and LVMI(echo) (r = 0.39, p < 0.05, n = 37) were all significantly correlated to 24-h systolic blood pressure, whereas maximal AIR and NIR were not. CONCLUSIONS: LV mass was related to NID and FMD, but not to AIR. The relationship to FMD was not independent of NID indicating that LV hypertrophy in patients with longstanding hypertension is more closely related to reduced overall vasodilatory capacity in the brachial artery than to endothelial dysfunction in conduit or subcutaneous resistance arteries. High LV mass and low NID were both related to high blood pressure, suggesting that vasodilatory capacity in conduit arteries is modified parallel to LV geometry by elevated blood pressure.     

Vasodilatory capacity and vascular structure in long-standing hypertension: a LIFE substudy. Losartan Intervention For Endpoint-Reduction in Hypertension

BACKGROUND: Flow-mediated dilatation (FMD), which is considered a measure of endothelial function, has been found impaired in hypertension. However, it is unclear whether this impairment is explained solely by endothelial dysfunction, or whether it is associated with structural vascular changes and reduced vasodilatory capacity. METHODS: In 42 unmedicated patients with hypertension and electrocardiographic left ventricular hypertrophy, we measured the following: 24-h ambulatory blood pressure (BP), minimal forearm vascular resistance (MFVR) by plethysmography, intima-media cross-sectional area of the common carotid arteries (IMA), FMD, and nitroglycerin-induced dilatation (NID) in the brachial artery by ultrasound. RESULTS: We found that FMD was correlated positively with NID (r = 0.38, P < .05). However, FMD as well as NID correlated negatively to 24-h systolic BP (r = -0.41, P = .01 and r = -0.52, P = .001), IMA/height (r = -0.41, P < .01 and r = -0.53, P < .001) and MFVR(men) (r = -0.44, P < .05 and r = -0.42, P < .05). CONCLUSIONS: Low FMD as well as low NID were related in parallel to high systolic BP and to the severity of vascular changes in different vascular beds, suggesting that elevated BP load in hypertension induces parallel abnormalities in conduit artery structure and overall vasodilatory capacity. Therefore, the decrease in FMD observed in severe hypertension may be caused by endothelial dysfunction as well as by structural vascular changes, suggesting difficulties in interpreting FMD solely as a measure of endothelial dysfunction in hypertensive patients with left ventricular hypertrophy.     

Systolic and diastolic hypertension impair endothelial vasodilatory function in different types of vessels in the elderly: the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study

BACKGROUND: Endothelium-dependent vasodilation (EDV) is known to be impaired in middle-aged hypertensive individuals, but less is known regarding hypertension in the elderly. OBJECTIVE: In the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS) study, different techniques to evaluate EDV in resistance and conduit arteries were applied in elderly subjects and were related to the type of hypertension. DESIGN AND METHODS: 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 dilatation (FMD) and pulse wave analysis with a beta-2 receptor agonist challenge, terbutaline. Those without antihypertensive treatment were divided into three groups: normotensive individuals (n = 256), and those with isolated systolic hypertension (n = 309) or combined systolic/diastolic hypertension (n = 79). RESULTS: Compared with normotensive individuals, EDV was reduced in those with combined systolic/diastolic hypertension only (P = 0.0019), whereas FMD was mainly reduced in those with isolated systolic hypertension (P = 0.013). Furthermore, in regression analysis, EDV was related to diastolic blood pressure only (r = -0.10, P = 0.017), whereas FMD was mainly related to systolic blood pressure (r = -0.13, P = 0.0023). The pulse wave-based method to analyse vasoreactivity was not consistently affected by hypertension. CONCLUSIONS: In elderly subjects, systolic hypertension mainly impairs conduit artery endothelial vasodilatory function, whereas diastolic hypertension mainly induces dysfunction in resistance arteries.     

Intima Media Thickness and Endothelial Function in Chronic Hemodialysis Patients

The purpose of our study was to evaluate the intima‐media thickness (IMT) of the carotid and brachial arteries, flow‐mediated dilatation (FMD), and nitroglycerin‐mediated dilatation (NMD) in diabetic and non‐diabetic hemodialysis patients. We also examined the effects of traditional and other risk factors on carotid and brachial IMT, FMD and NMD in all hemodialysis patients. Fifty‐eight adult hemodialysis patients, 14 of whom had diabetes, were studied. They had been on hemodialysis for 1–340 months. Using B‐mode ultrasonography, we measured the carotid and brachial IMT, FMD and NMD, and correlated the values with cardiovascular risk factors. FMD and NMD were significantly lower in diabetic patients (FMD 4.01 ± 0.99 vs. 6.69 ± 2.37 mm; NMD 9.1 ± 1.95 vs. 11.23 ± 2.86 mm), while no such differences were found between the two groups with respect to carotid or brachial IMT. In all patients with respect to age a positive correlation was found with carotid and brachial IMT, and a negative one with FMD and NMD. With respect to hypertension as well as diabetes, a negative correlation was found with FMD and NMD. Age is the most important factor that significantly affected all studied markers of atherosclerosis in hemodialysis patients. The endothelial and smooth vascular functions are significantly impaired in diabetic and hypertensive hemodialysis patients, and hypertension is shown to be an independent risk factor for smooth vascular dysfunction in hemodialysis patients. According to our results, intensive antihypertensive treatment is recommended in hypertensive chronic hemodialysis patients.     

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.     

Endothelial function in conduit and resistance arteries in men with coronary disease

The aims of this study were to determine whether non-invasive measurement of endothelial function in conduit arteries reflects that of subcutaneous resistance arteries measured in vitro and to examine whether there is an endothelial dysfunction also in resistance arteries in patients with a previous myocardial infarction. The brachial artery diameter responses to a hyperemic flow stimulus and an in vitro method, pressure myography, to directly evaluate flow-mediated responses in arteries obtained from biopsies of subcutaneous fat were measured in 25 patients with a previous myocardial infarction and in 8 aged matched healthy subjects. Flow-mediated dilatation of the brachial artery was more pronounced in the healthy group compared with the group with coronary disease, 5.1 +/- 2.5% and 2.6 +/- 2.1%, respectively (p < 0.05). The flow-mediated dilatation in subcutaneous arteries from CHD patients was significantly reduced compared to control subjects (e.g. percent change from initial preconstriction at maximum flow rate of 204 microl/min: 42 +/- 7% CHD (n = 25) versus 84 +/- 24% control (n = 8), ANOVA, p = 0.03). There was a significant correlation between flow-mediated dilatation of the brachial artery and maximum flow-mediated dilatation at microvascular level, (p < 0.01). In conclusion this study demonstrates endothelial dysfunction in both conduit and resistance circulation in patients after myocardial infarction compared to an aged-matched healthy control group. Furthermore, a significant and independent relationship between endothelial function by means of flow-mediated dilatation in large conduit arteries and resistance arteries was observed.     

原发性高血压合并高尿酸血症患者血管内皮依赖性舒张功能变化及临床意义

目的探讨原发性高血压（EH）合并高尿酸血症患者血管内皮依赖性舒张功能的变化及意义。方法选择EH患者30例、EH合并高尿酸血症患者60例及健康体检者30例,采用无创性高分辨超声技术检测三组休息、反应性充血、舌下含服硝酸甘油（GTN）后肱动脉内径的变化。结果EH及EH合并高尿酸血症患者肱动脉血流介导性扩张百分比明显低于正常组（P〈0．05）,EH合并高尿酸血症患者下降更明显（P〈0．01）;舌下含服GTN后EH合并高尿酸血症组肱动脉内径变化与正常对照组比较有统计学差异（P〈0．05）,EH组与正常对照组之间无统计学差异。结论EH合并高尿酸血症患者存在血管内皮依赖性舒张功能失调,高尿酸血症可加重血管内皮依赖性舒张功能的损害。     

高频超声检测高血压患者血管内皮舒张功能的探讨

目的：探讨高频超声检测高血压患者血管内皮依赖性舒张功能的临床价值。方法：应用高频超产检测高血压患者（25例）和正常血压患者（18例）休息、反应性充血时,舌下含服硝酸甘油后肱动脉内径的变化。结果：内皮依赖性血管舒张功能高血压组较正常血压组明显减弱（7.14±3.20）%∶（13.71%±6.3）%（P〈0.01）,高血压组和正常血压组比较血管内皮非依赖性舒张功能无显著性差异（P〉0.05）。结论：高血压患者存在血管内皮依赖性舒张功能失调,高频超声能准确可靠地检测血管内皮依赖性舒张功能。     

Association of cardiovascular risk factors with microvascular and conduit artery function in hypertensive subjects

BACKGROUND: Alterations in microvascular and conduit artery function contribute to target organ damage in hypertension. We investigated the association of cardiovascular (CV) risk factors with microvascular and conduit artery function in hypertensive subjects. METHODS: Participants included 504 hypertensives (aged 62.1 +/- 9.8 years, 42% men) from the community, without history of symptomatic CV disease. Brachial artery ultrasound was performed to measure forearm blood flow (FBF) at rest and during reactive hyperemia (markers of microvascular function) and flow-mediated dilatation (FMD) of the brachial artery (a marker of conduit artery endothelial function). The association of conventional and novel (homocysteine, C-reactive protein, fibrinogen, and lipoprotein a CV risk factors with microvascular function and FMD was tested in multivariable regression models. RESULTS: Variables independently associated with higher resting FBF were male sex, higher body mass index (BMI), smoking, and lower HDL-cholesterol; variables associated with lower hyperemic FBF included greater age, female sex, and diabetes. Higher plasma homocysteine was associated with lower hyperemic FBF in obese subjects (P for log homocysteine x BMI interaction = .0008). Variables independently associated with lower FMD were greater age, sex gender, history of smoking, and not using statins. Higher homocysteine was associated with lower FMD in subjects with higher systolic blood pressure (P for interaction = .0004). Hyperemic flow velocity was independently associated with FMD (P = .0006), but its inclusion as a covariate did not influence the association of CV risk factors with FMD. CONCLUSIONS: In asymptomatic subjects with essential hypertension, select CV risk factors were associated with microvascular and conduit artery function. Furthermore, the association of CV risk factors with conduit artery function appeared to be independent of downstream microvascular function.     

Evaluation of endothelial function in hypertensive elderly patients by high-resolution ultrasonography.

BACKGROUND: Multiple investigations, both in experimental models and in middle-aged patients with essential hypertension, demonstrate impaired endothelium-dependent vasodilatation. HYPOTHESIS: We attempted to determine whether hypertension still exerts additional negative effect on endothelial function of large arteries in hypertensive elderly patients who may already be affected by endothelial dysfunction due to aging. METHODS: We compared 13 elderly patients with hypertension [69 +/- 9 years, (mean +/- standard deviation)] with 13 matched healthy elderly subjects (72 +/- 6 years) as controls. Using high-resolution vascular ultrasound, we measured brachial artery responses to reactive hyperemia (with increased flow causing endothelium-dependent dilatation) and sublingual nitroglycerin (causing endothelium-independent dilatation). RESULTS: Flow-mediated dilatation correlated inversely with age (r = -0.60, p = 0.03) in the controls. Flow-mediated dilatation was significantly impaired in hypertensive elderly patients (6.7 +/- 3.3 vs. 13.3 +/- 1.8% in controls, p < 0.0001). No significant difference could found in nitroglycerin-induced dilatation between controls (12.1 +/- 4.9%) and hypertensive elderly patients (10.2 +/- 6.8%, p = 0.5). On multivariate analysis, flow-mediated dilatation in hypertensive elderly patients was inversely related to aging (r = -0.37, p = 0.04) and mean blood pressure (r = -0.57, p = 0.03). CONCLUSIONS: Our study showed decreased flow-mediated dilatation with aging even in the healthy controls, and further decline in flow-mediated dilatation in hypertensive elderly patients compared with controls. This impairment of flow-mediated dilatation in hypertensive elderly patients was related to age and mean blood pressure, indicating that aging and hypertension may independently impair endothelial function in the brachial artery of these patients.     

Impaired myocardial perfusion reserve but preserved peripheral endothelial function in patients with Fabry disease

Summary Fabry disease (McKusick 301500) is an X-linked lysosomal storage disorder due to deficient α-galactosidase A activity, which leads to accumulation of glycosphingolipids, especially in vascular smooth-muscle and endothelial cells. The effect of this accumulation on peripheral and cardiac vascular function is poorly known. We studied 15 Fabry patients (mean age 35 years and mean BMI 24.8 kg/m2) and 30 age- and BMI-matched healthy controls to examine whether myocardial perfusion reserve and peripheral artery endothelial function are altered. Myocardial perfusion was measured at rest and during dipyridamole-induced hyperaemia by positron emission tomography and H₂ ¹⁵O. Myocardial blood flow reserve was calculated as the ratio between the dipyridamole-induced maximal blood flow and resting blood flow. Peripheral artery endothelial function was assessed by measuring the brachial artery flow-mediated dilatation using ultrasound at rest and during reactive hyperaemia. The myocardial perfusion reserve was significantly lower in Fabry patients than in controls (3.3 ± 1.2 vs 4.4 ± 1.6, p = 0.02), while the brachial artery flow-mediated dilatation was similar (5.9% ± 3.9%vs 4.5% ± 3.6%, p = 0.27). Thus, inFabry disease, myocardial perfusion reserve is reduced while the peripheral artery endothelial function is preserved.     

Measurement of flow-mediated dilatation of the brachial artery is affected by local elastic vessel wall properties in high-risk patients

OBJECTIVES: To assess whether the validity of endothelial function measurement by flow-mediated dilatation (FMD) is affected by local brachial artery stiffness (distensibility coefficient; DC) and arterial wall thickness (intima-media thickness, IMT). BACKGROUND: FMD measurement relies on assessment of arterial diameter change. Increased IMT and decreased DC might physically limit dilatation of the brachial artery in spite of healthy endothelium. METHODS: DC, IMT and FMD of the brachial artery were simultaneously measured in 349 patients with advanced atherosclerosis or cardiovascular risk factors. The relations between FMD and age, and FMD and current smoking were regarded as a proxy for the relation between FMD and true endothelial function. RESULTS: The relations between FMD and age, and FMD and smoking, were significantly modified by brachial artery DC. No modification was found for IMT. The interaction terms were statistically significant (p=0.03 and 0.04, respectively). The relation between FMD and age, and FMD and smoking was progressively more pronounced in patients with more elastic arteries. CONCLUSION: The results of our study indicate that increased arterial stiffness may interfere with valid measurement of FMD and that patients with stiff arteries may be considered for exclusion from analyses involving FMD to ensure its validity.     

Protective effect of high density lipoprotein on endothelium-dependent vasodilatation

Low concentrations of high-density lipoprotein cholesterol (HDL-C) have been associated with increased risk of coronary heart disease (CHD) even when the total cholesterol (TC) and triglyceride (TG) levels are not elevated. The mechanism by which HDL confers protection against atherosclerosis remains speculative. Using high-resolution ultrasound, we measured the dilatation changes of brachial arteries during reactive hyperemia and after sublingual glyceryl trinitrate (GTN) in 63 patients with established (CHD) and 45 controls, in which the serum TC level was normal. The results showed that both flow-mediated dilatation (FMD) and GTN-induced dilatation of brachial arteries in patients with CHD were much reduced compared with control group (2.31+/-2.46% vs. 7.43+/-4.10% and 16.41+/-6.15% vs. 22.44+/-8.63%, respectively, P<0.001 for all). Univariate analysis indicated that FMD of brachial arteries was inversely related to age (r=-0.226, P<0.05), hypertension (r=-0.229, P<0.05), baseline diameter (r=-0.299, P<0.01) and LDL-C (r=-0.237, P<0.05) and positively related to HDL-C (r=0.491, P<0.01). GTN induced vasodilatation was inversely related to age (r=-0.216, P<0. 05) and baseline diameter (-0.476, P<0.01). Multiple stepwise regression analyses in two groups taken together showed that HDL-C and age were the independent predictors of the FMD of brachial arteries (beta=0.466, P=0.000 and beta=-0.184, P=0.020, respectively). Baseline diameter was significant predictor of GTN-induced vasodilatation (beta=-0.390, P=0.000). The analysis in the group of CHD patients showed that only HDL-C was significantly relate to the FMD of brachial arteries (beta=0.295, P=0.018 ) and in controls that hypertension and HDL-C were significantly relate to the FMD of brachial arteries (beta=-0.395, P=0.004 and beta=0.344, P=0.011, respectively). These finding suggest that endothelium-dependent and endothelium-independent vasodilatation are impaired in the patients with CHD. HDL exerts a protective effect on endothelium-dependent vasodilatation in TC being relatively normal population.     

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.     

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.     

Benefits of statin treatment in cardiac syndrome-X1.

AIMS: The pathophysiological mechanism in cardiac syndrome-X (anginal chest pain, positive exercise test, and angiographically normal coronary arteries) has been suggested as an impairment in normal endothelial function of the coronary microvasculature, resulting in inadequate flow reserve. The aim of this study was to determine whether statins with proven beneficial effects on endothelium, have any effect on endothelial functions and exercise induced ischaemia in cardiac syndrome-X. METHODS AND RESULTS: Study population consisted of prospectively enrolled 40 patients with cardiac syndrome-X. Patients with left ventricular hypertrophy, hypertension, diabetes mellitus, and LDL levels >/=160 mg/dl were excluded. Half of the patients received pravastatin (40 mg/day) for 3 months irrespective of their lipid values, according to a single-blind, randomized, placebo-controlled design. Endothelial functions were assessed with high-resolution vascular ultrasound, which measured the brachial artery flow mediated dilatation (FMD). Lipid measurements, symptom limited exercise tests and vascular ultrasound images were obtained before and at the end of 3 months. After the treatment, FMD improved significantly in pravastatin group. Exercise duration, and time to 1mm-ST depression were significantly prolonged after statin therapy. Ischaemic symptoms and ECG findings during exercise test disappeared completely in 5 (26%) patients in the statin group. However, there were no significant changes in FMD and exercise parameters in placebo group. CONCLUSIONS: Statin therapy resulted in beneficial effects on both exercise induced ischaemia and FMD in cardiac syndrome-X. The mechanism of this beneficial effect is probably the result of improvement in endothelial functions.     

Left ventricular mass is related to endothelium-dependent vasodilation in the forearm, but not in the brachial artery, in elderly subjects: the Prospective Investigation of the Vasculature in Uppsala Seniors study

Left ventricular hypertrophy (LVH) is a powerful cardiovascular risk factor and has previously been related to endothelium-dependent vasodilation (EDV) in hypertensive patients. In the Prospective Investigation of the Vasculature in Uppsala Seniors study, different techniques to evaluate EDV in different types of vessels were applied and were related to left ventricular mass index (LVMI) in the general population. In 1016 subjects aged 70 years, EDV was evaluated by the invasive forearm technique with acetylcholine given in the brachial artery, the brachial artery ultrasound technique with measurement of flow-mediated dilatation (FMD) and the pulse wave analysis method with beta-2-agonist (terbutaline) provocation. LVMI was determined by echocardiography. LVMI was related to both EDV and the pulse wave-based technique (both r = -0.14, P < 0.0001) in univariate analysis. LVMI was also weakly related to FMD (r = -0.07, P = 0.046). However, in multiple regression analysis adjusted for gender, systolic and diastolic blood pressure and use of antihypertensive medication, only EDV was associated with LVMI (P = 0.016). EDV was mainly reduced in those with left ventricular concentric hypertrophy (P = 0.0012). In conclusion, in a population-based sample of elderly subjects, EDV, but not FMD, was inversely correlated with LVM independent of blood pressure, suggesting that EDV in resistance arteries is of more importance for LVH than endothelial vasodilatory function in conduit arteries in the elderly.