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.     

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.     

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

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

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.     

高血压患者动脉缓冲功能和内皮调节功能临床研究

研究高血压患者动脉缓冲功能和内皮调节功能的损害 ,为临床选择敏感反映高血压患者预后危险性的指标。对 54例原发性高血压患者和 16例正常人应用自动脉搏波速度 (PulsewavevelocityPWV)测定仪进行检测 ,颈动脉 -股动脉PWV(CPWV)作为反映动脉扩张性 (Distensibility)的参数 ,并能敏感反映动脉缓冲功能的改变。二维超声分别测定肱动脉横断面顺应性 (CSC) ,容积扩张性 (VD)和内皮依赖性血管扩张功能用于评价动脉缓冲功能和内皮功能。CPWV在高血压组显著升高 (P =0 .0 4 83) ,CSC ,VD高血压组显著低于正常对照组(P =0 .0 30 2 ,P =0 .0 196 ) ,内皮依赖性血管扩张功能在高血压组显著降低 (P =0 .0 130 )。多因素分析结果表明VD是与内皮功能关系最为密切的因素 (r =0 .3995,P =0 .0 0 11)。结论为高血压可导致动脉缓冲功能和内皮功能的损害 ,内皮功能障碍是动脉缓冲功能降低的原因。二维超声检测动脉扩张性的改变能敏感反映高血压患者动脉缓冲功能和内皮功能的损害 ,为临床提供了一个重要的无创指标 ,具有广阔的应用价值。     

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.     

老年H型高血压患者踝臂指数变化的临床意义

目的探讨老年H型高血压患者踝臂指数(ABI)的异常情况及临床意义。方法选择127例患者,根据血浆高同型半胱氨酸和诊室血压水平分为H型高血压组(HH组)65例、非H型高血压组(NHH组)32例和正常血压组(NT组)30例。测定ABI、高敏C反应蛋白(hs-CRP)、髓过氧化物酶(MPO)水平和血管内皮功能。结果与NT组比较,HH组和NHH组ABI明显降低(P<0.05,P<0.01);与NHH组比较,HH组ABI明显降低(P<0.05)。与NT组比较,HH组MPO、hs-CRP明显升高,内皮依赖性舒张功能(FMD)明显降低(P<0.05,P<0.01);与NHH组比较,HH组FMD明显降低(P<0.05)。相关分析显示,HH组ABI与hs-CRP和MPO呈负相关(r=-0.739、r=-0.723,P<0.01),与FMD呈正相关(r=0.927,P<0.01)。结论 ABI降低与炎性反应及血管内皮功能受损密切相关,对评估老年H型高血压患者动脉功能损害及识别高危患者有重要的临床意义。     

Assessment of Endothelial Function in Alzheimer's Disease: Is Alzheimer's Disease a Vascular Disease?

OBJECTIVES: To compare endothelial function of people with Alzheimer's disease (AD) with that of people without. DESIGN: Case-control study. SETTING: Geriatric medicine outpatient clinic of a university hospital. PARTICIPANTS: Twenty-five patients with AD who were free of vascular risk factors and 24 healthy elderly controls were enrolled. Exclusion criteria were diabetes mellitus, hypertension, dyslipidemia, evident stroke, smoking, documented coronary artery disease, history of myocardial infarction, heart failure, acute or chronic infection, malignancy, peripheral artery disease, renal disease, rheumatologic diseases, alcohol abuse, and certain drugs that may affect endothelial function. Both groups underwent comprehensive geriatric assessment and neuropsychiatric assessment. MEASUREMENTS: Endothelial function was evaluated according to flow-mediated dilation (FMD) from the brachial artery. RESULTS: Mean age +/- standard deviation was 78 +/- 5.9 in the group with AD (11 female and 14 male) and 72.1 +/- 5.8 in the control group (9 female and 11 male). Multiple linear regression analysis revealed that FMD was significantly lower in patients with AD (median 3.45, range 0-7) than controls (median 8.41, range 1-14) (P < .001), independent of age. It was also found that FMD values were inversely correlated with the stage of the disease as determined according to the Clinical Dementia Rating scale (r=-0.603, P < .001). CONCLUSION: Endothelial function is impaired in patients with AD. Endothelial function was worse in patients with severe AD. These findings provide evidence that vascular factors have a role in the pathogenesis of AD.     

Low-density lipoprotein subfractions and cardiovascular risk in hypertension: relationship to endothelial dysfunction and effects of treatment

Although hypertensive patients are at particular risk of vascular complications, the possible contribution of an atherogenic lipoprotein profile and endothelial dysfunction to this risk is unclear. We investigated this by measuring LDL subfractions and flow-mediated dilation (FMD) (reflecting endothelial dysfunction) in a cohort of high-risk hypertensive patients. We studied 84 hypertensive patients (74 men; mean age, 64 years; SD 8). Chylomicron-free LDL subfractions were analyzed by disc polyacrylamide gel electrophoresis, producing an LDL score, with higher scores being equivalent to a greater proportion of the more atherogenic LDL subfractions. High-resolution ultrasound was used to assess endothelium-dependent brachial artery FMD after reactive hyperemia after vessel occlusion. Baseline levels were compared with 61 age- and gender-matched healthy normotensive control subjects. Mean LDL score was higher and FMD impaired in hypertensive subjects compared with control subjects. These indexes were significantly improved after 6 months of cardiovascular risk factor management. LDL score correlated significantly with the 10-year Framingham coronary heart disease risk score, with a negative correlation with FMD (both P<0.001). Abnormal atherogenesis and endothelial dysfunction are both present in hypertension and appear to be related to each other, potentially leading to vascular complications. The abnormal LDL scores also correlate with the 10-year cardiovascular risk and can be positively influenced by cardiovascular risk management.     

Effects of losartan versus hydrochlorothiazide on indices of endothelial damage/dysfunction, angiogenesis and tissue factor in essential hypertension

BACKGROUND: Abnormalities in endothelial function, angiogenesis and thrombogenesis are found in essential hypertension. Angiotensin II has been postulated as an agent involved in these processes. We hypothesized that the treatment of essential hypertension with the angiotensin II receptor antagonist, losartan, would affect endothelial damage/dysfunction, angiogenesis and coagulation, when compared to treatment with a diuretic. METHODS: Forty hypertensive patients (28 male, mean age 56 +/- 11.8 years) were randomized to treatment with losartan 50-100 mg o.d. or hydrochlorothiazide 12.5-25 mg o.d. over a 12-week period. Patients were assessed at week 0, 4 and 12. Endothelial damage/dysfunction was assessed using plasma levels of von Willebrand factor (vWf) and changes in flow-mediated dilation of the brachial artery (FMD). Vascular endothelial growth factor (VEGF) and its soluble receptor Flt-1 (sFlt-1) were measured as indices of angiogenesis, and plasma tissue factor (TF) as an index of coagulation. Baseline results in hypertensives were compared to 20 healthy controls (13 male, mean age 61.1 +/- 10.1 years). Results: Mean patient BP was 161/95 +/- 21/18 mmHg compared to 134/81 +/- 11/7 mmHg in controls (p<0.002). Plasma levels of TF (p=0.023) were significantly higher in patients compared to controls, and FMD was significantly lower (p<0.001). There were no significant differences in baseline blood pressures, plasma indices or FMD between patients randomized to losartan and hydrochlorothiazide. There were no significant changes in levels of plasma indices or FMD over 12 weeks of treatment in either patient group. Significant correlations between levels of VEGF with sFlt-1 (Spearman p<0.001) and TF (p=0.009) and sFlt-1 and TF (p=0.035) were seen in the untreated state, amongst the patient group only. CONCLUSION: We have confirmed previous observations of increased levels of TF and decreased FMD in hypertensive patients compared to healthy controls. Contrary to previous observations in higher-risk hypertensive patient groups, the treatment of essential hypertension with either losartan or hydrochlorothiazide did not affect indices of endothelial damage/dysfunction, angiogenesis or coagulation.     

Vascular endothelial function in patients with slow coronary flow

BACKGROUND: Slow coronary flow (SCF) in a normal coronary angiogram is a well-recognized clinical entity, but its etiopathogenesis remains unclear. DESIGN: The aim of the study was to determine endothelial function in patients with SCF using a flow-mediated dilatation (FMD) technique in the brachial artery. METHODS: Coronary flow was quantified using the corrected thrombosis in myocardial infarction (TIMI) frame count (CTFC) method. Endothelial function was studied in 27 patients with SCF (23 men, four women, mean age 47.6+/-8.7 years) and in 30 people with normal coronary flow (NCF) (22 men and eight women, mean age 47.5+/-7.4 years). RESULTS: The flow-mediated diameter increase in the SCF group was significantly smaller than that in the NCF group (3.48+/-0.10% compared with 9.11+/-0.10%, P < 0.001). The percentage of nitroglycerine (NTG)-induced dilatation was not significantly different between patients with SCF and people with NCF (16.8+/-1.1% compared with 17.1+/-1.1%, P = 0.87). Simple regression analysis showed that mean CTFC (CTFC(m)) was strongly and inversely related to the percentage of FMD (r = -0.29, P < 0.01) in all participants. When the patients with SCF were excluded, CTFC(m) was still inversely related to the percentage of FMD (r = -0.36, P < 0.05). CTFC(m) was also inversely related to NTG-induced dilatation in the 57 participants (r = -0.23, P < 0.05). Multiple regression analysis showed that CTFC(m) was inversely related to the percentage of FMD only (r = -0.37, P < 0.05). CONCLUSIONS: These findings suggest that endothelial function is impaired in people with SCF and that CTFC correlates well with endothelial dysfunction.     

Endothelial dysfunction precedes atherosclerosis in systemic sclerosis--relevance for prevention of vascular complications

OBJECTIVES: The pathogenesis of systemic sclerosis (SSc) includes vasculopathy with endothelial dysfunction. The aim of this study was to investigate endothelium-dependent, flow-mediated dilatation (FMD), as well as endothelium-independent, nitroglycerin-mediated dilatation (NMD) of the brachial artery and to assess common carotid intimal-medial thickness (ccIMT) in SSc patients compared with healthy controls. METHODS: FMD and NMD of the brachial artery were determined using high-resolution ultrasound imaging and the values were expressed as percentage change from baseline in 29 SSc patients and 29 healthy controls. The two groups were very similar regarding sex, age and traditional cardiovascular risk factors. In addition, common carotid arteries were assessed by duplex colour ultrasound, ccIMT determined using high resolution ultrasound and expressed in mm thickness in the same patients and controls. Correlations between FMD, NMD, ccIMT, age and the SSc subtype (diffuse or limited form) were analysed. RESULTS: In the 29 SSc patients (mean age: 51.8 yrs), the FMD was significantly lower (4.82 +/- 3.76%) in comparison with the controls (8.86 +/- 3.56%) (P < 0.001). No difference was found in NMD between patients (19.13 +/- 17.68%) and controls (13.13 +/- 10.40%) (P > 0.1). There was a tendency of increased ccIMT in SSc patients (0.67 +/- 0.26 mm) compared with healthy subjects (0.57 +/- 0.09), but this difference was not significant (P = 0.067). A significant, positive correlation between ccIMT and age in SSc (r = 0.470, P = 0.013) was detected, as well as in healthy controls (r = 0.61, P = 0.003), but no correlation was found between FMD and age. In addition, ccIMT, but not FMD and NMD, displayed significant correlation with disease duration (r = 0.472, P = 0.011). NMD displayed significant inverse correlation with the age in SSc patients (r = -0.492, P = 0.012), but not in controls. We did not find any correlation between FMD, NMD, ccIMT and SSc subtype. CONCLUSIONS: There is an impairment of endothelium-dependent vasodilatation indicated by low FMD in SSc. At the same time, the endothelium-independent dilatation assessed by NMD is still preserved giving an opportunity of nitroglycerine therapy. Carotid atherosclerosis indicated by ccIMT may occur at higher ages and after longer disease duration. Thus, the assessment of FMD in the pre-atherosclerotic stage may have a beneficial diagnostic, prognostic and therapeutic relevance.     

Maladaptive arterial remodeling with systemic hypertension associated with increased concentrations in blood of plasminogen activator inhibitor type-1 (PAI-1)

Increased carotid artery intima-media thickness (IMT), but not necessarily peripheral vessel IMT, accompanies atherosclerosis. We hypothesized that IMT in a peripheral, muscular artery known to be resistant to atherosclerotic changes would increase with hypertension, thereby limiting increases in wall stress and potentially preserving endothelial cell function reflected by flow-mediated dilation (FMD). Plasminogen activator inhibitor type-1 (PAI-1) can inhibit vascular smooth muscle cell migration contributing to increased IMT. Thus, increased PAI-1 may attenuate the mural adaptive response. A high-resolution scanner designed to delineate brachial artery FMD and IMT was used in studies of previously untreated patients with essential hypertension (n = 18) and age- and gender-matched normotensive subjects (n = 15). Brachial IMT was increased with hypertension (0.36 +/- 0.07 vs 0.27 +/- 0.03 mm in controls, p <0.01), and FMD was lower (3.6 +/- 1.5% vs 7.8 +/- 3.6, p <0.01). PAI-1 antigen in blood was increased (40.5 +/- 31.8 vs 26.3 +/- 11.6 ng/ml, p <0.05). IMT and FMD correlated positively (r = 0.63, p <0.05) in hypertensive patients. FMD correlated inversely with wall stress (r = -0.57, p <0.05). IMT correlated inversely with PAI-1 (r = -0.61, p <0.05). These observations support the hypothesis that increased PAI-1 attenuated increases in neointimal vascular smooth muscle cell cellularity. Thus, increased PAI-1 may attenuate a mural, adaptive response to hypertension associated with preservation of endothelial cell function.     

Atorvastatin therapy improves endothelial-dependent vasodilation in patients with systemic lupus erythematosus: an 8 weeks controlled trial

INTRODUCTION: Patients with systemic lupus erythematosus (SLE) have recognized reduction in endothelium-dependent vasodilation. Evidence demonstrates that statins are able to improve endothelial function independently on their hypolipemic action. OBJECTIVES: To evaluate the efficacy of atorvastatin in improving vasodilation in SLE patients with and without conventional risk factors for coronary heart disease (CHD). PATIENTS AND METHODS: Sixty-four SLE women, mean age 31 +/- 8 yrs, received atorvastatin 20 mg/day during 8 weeks. Thirty-one patients in this intervention group did not have conventional risk factors for CHD, while 33 others had hypertension, dyslipidaemia and/or obesity. Twenty-four SLE control patients, mean age 34 +/- 7.5 yrs, not receiving atorvastatin were followed during the same time period. High-resolution ultrasound was used to measure brachial artery diameter in resting conditions, during reactive hyperaemia and after sub-lingual glyceryl trinitrate (GTN). Measurements were performed at baseline and at the end of the study (8 weeks). RESULTS: Atorvastatin was associated with a significant increase in flow-mediated dilation (FMD) [3.8 (2.8-7.9%) vs 6.9 (4.2-10.7%), P < 0.001] while GTN-mediated dilation (GTND) was unaffected [20.9 (16.6-26.1%) vs 20.1(16.6-25.4%), P = 0.514]. FMD increase was observed in patients with conventional risk factors [4.1 (3.1-8.7%) vs 6.5 (4-10%), P = 0.046] and also for those without conventional risk factors for CHD [3.6 (2.6-7.3%) vs 7.1 (4.5-10.9%), P = 0.001]. Resting brachial artery diameter also increased significantly in patients receiving atorvastatin (2.79 +/- 0.30 mm vs 2.92 +/- 0.40 mm, P < 0.001). No significant difference in artery diameter and FMD was seen in control patients at the end of the study. When compared to the control patients, atorvastatin treatment was associated with significant increase in resting diameter (+0.13 +/- 0.1 mm vs -0.02 +/- 0.07 mm, P < 0.001) and FMD (+1.9 +/- 3.9% vs -0.3 +/- 1.8%, P = 0.009). CONCLUSION: Our results demonstrate that an 8-week 20 mg/day atorvastatin series improved endothelium-dependent vasodilation in SLE patients independently on the presence of conventional risk factors for atherosclerotic disease.     

Effect of sulfhydryl and non-sulfhydryl angiotensin-converting enzyme inhibitors on endothelial function in essential hypertensive patients

BACKGROUND: Oxidative inactivation of nitric oxide (NO) is regarded as an important cause of reduced endothelium-dependent vasodilation in essential hypertension. Because zofenopril, an angiotensin-converting enzyme (ACE) inhibitor with a sulfhydryl (SH) group, has demonstrated antioxidant properties and to reduce adhesion molecule expression in vitro, in this study we evaluated the effect of this drug in comparison with the carboxylic ACE inhibitor ramipril and the beta-adrenoreceptor blocker atenolol on (1) circulating adhesion molecules and some oxidative stress parameters and (2) endothelium-dependent vasodilation in essential mildly hypertensive patients. METHODS: A total of 45 healthy subjects and 45 matched hypertensive patients participated in the study. Hypertensive patients were randomly treated with zofenopril (15 to 30 mg/d), ramipril (2.5 to 5 mg/d), and atenolol (50 to 100 mg/d). At baseline and after an 8-week therapy we evaluated blood pressure (BP) values, plasma and LDL hydroperoxides, plasma 8-isoprostanes, circulating levels of oxidized-(ox)LDL and of adhesion molecules (intercellular cell adhesion molecule-1 [ICAM-1], and vascular cell adhesion molecule-1 [VCAM-1], and E-selectin). Furthermore, all patients underwent ultrasound detection of brachial artery reactivity and endothelium-dependent dilation (flow-mediated dilation, FMD) was evaluated. RESULTS: All the treatments determined similar significant (P < .001) reduction of both systolic and diastolic BP values. Plasma (P < .01) and LDL hydroperoxides (P < .01), plasma 8-isoprostanes (P < .05), circulating oxLDL (P < .05), and adhesion molecules (P < .05) were significantly reduced only in patients receiving zofenopril. Similarly FMD was significantly increased (P < .001) in the zofenopril-treated group. CONCLUSIONS: Our results suggest that in mildly hypertensive patients without organ damage zofenopril, beyond its BP-lowering effects and through its sustained antioxidant activity, offers important advantages in reducing endothelial activation.     

Effect of local and remote ischemic preconditioning on endothelial function in young people and healthy or hypertensive elderly people

To verify whether age affects remote preconditioning, we compared healthy young people (mean age = 28.0 years, SD: 7.2), healthy elderly people (age = 69.2 years, SD: 5.0), and hypertensive elderly people (group 3, age = 72.8 years, SD: 3.9). Each group included 10 participants. The flow-mediated-dilation (FMD) was measured after local (same arm) and remote (leg) ischemic preconditioning.Healthy elderly people had the greatest increase of FMD after ischemic preconditioning compared to baseline (173% after local and 181% after remote preconditioning) and young participants the smallest increase (77% after local and 69% after remote preconditioning) while hypertensive elderly had an intermediate increase (P for comparison across groups: 0.347 for local and 0.064 for remote preconditioning). However, absolute values of FMD after preconditioning were much lower in elderly hypertensive than in healthy young adults.Remote preconditioning increases endothelial reactivity in healthy and hypertensive elderly. The potential clinical relevance of this finding deserves consideration.     

Endothelial dysfunction in Type 2 diabetic subjects with and without microalbuminuria.

AIMS: The primary aim of this study was to determine whether microalbuminuria is associated with endothelial dysfunction in Type 1 diabetes mellitus. The secondary aim was to determine whether any reported biochemical markers of cardiovascular risk are associated with endothelial dysfunction in this group. METHODS: Measurements were made of the vasodilatory responses of the brachial artery to post-ischaemic hyperaemia and to sublingual glyceryl trinitrate (GTN) (causing endothelium-dependent and endothelium-independent dilation, respectively) using a high-resolution ultrasound technique in 18 Type 1 diabetic patients with microalbuminuria, 18 age and sex-matched normoalbuminuric Type 1 diabetic patients and 18 non-diabetic control subjects. RESULTS: There was a significant reduction in flow-mediated dilation (FMD) in microalbuminuric and normoalbuminuric diabetic patients compared with control subjects (2.4% (95% confidence interval (CI) 1.0-3.8%) and 2.3% (95% CI 0.7-3.9%) respectively vs. 6.3% (95% CI 5.1-7.5%), P<0.0001) but no difference in GTN-mediated dilation (14.7% (95% CI 10.7-18.7%) and 15.2% (95% CI 11.2-19.2%) vs. 18.7% (95% CI 16.1-21.3%), P = 0.09). There was no significant difference in FMD, however, between the microalbuminuric group and normoalbuminuric group (P=0.45). FMD was not significantly associated with urinary albumin-creatinine ratio, glycosylated haemoglobin, plasma glucose, lipid or lipoprotein concentrations in diabetic patients. There was a positive correlation between active transforming growth factor (TGF)-beta concentration, a novel biochemical marker of macrovascular disease, and FMD in diabetic patients (r=0.36, P<0.05). GTN-mediated dilation was positively associated with HDL-cholesterol concentration (r = 0.49, P = 0.002) but not with other biochemical variables (including active TGF-beta concentration). Active TGF-beta concentration was not associated with degree of microalbuminuria or other biochemical parameters. CONCLUSIONS: These data suggest that endothelial dysfunction occurs in Type 1 diabetic patients regardless of urine albumin status. Endothelial dysfunction appears therefore to predate the development of microalbuminuria as a marker for the development of coronary artery disease. It is also concluded that low plasma levels of active TGF-beta are associated with an impaired endothelial response and this may provide a useful tool for identifying Type 1 diabetic patients at a greater risk of coronary artery disease.     

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.     

老年高血压病并下肢动脉硬化症的血管内皮功能

目的了解老年高血压病及高血压病合并下肢动脉硬化症(LEASD)患者内皮依赖性舒张功能(FMD)、非内皮依赖性舒张功能(NMD)以及血浆一氧化氮(NO)、内皮素(ET)的水平。方法采用高分辨率超声诊断系统分别检测36例老年高血压病(老年高血压组)患者以及49例老年高血压病合并LEASD(老年高血压合并LEASD组)患者肱动脉的FMD及NMD;同时采用硝酸盐镉还原、比色法测定NO水平(以硝酸盐浓度表示);采用放射免疫法检测ET水平,并分别与40例健康老人(健康老年组)进行对照研究。结果老年高血压合并LEASD组患者肱动脉的FMD及NMD均显著低于老年高血压组和健康老年组(P<0.05),而老年高血压组患者的FMD和NMD亦显著低于健康老年组(P<0.05);老年高血压合并LEASD组患者的NO水平显著低于老年高血压组和健康老年组,而ET却显著高于老年高血压组和健康老年组,而老年高血压组患者NO水平同样显著低于健康老年组,ET水平显著高于健康老年组(P<0.05)。结论老年高血压病及高血压病合并LEASD患者肱动脉FMD及NMD均受损;老年高血压病及高血压病合并LEASD患者均存在血管内皮功能失调,且高血压病合并LEASD患者内皮功能紊乱更严重。