高密度脂蛋白对血管内皮依赖性舒张功能的影响

目的　探讨血清高密度脂蛋白 胆固醇 (HDL C)水平与肱动脉内皮依赖性舒张功能之间的关系。方法　测定 71例血清总胆固醇水平相对正常的冠心病患者和 34例对照者的血脂水平以及在反应性充血时和含服硝酸甘油后肱动脉的内径变化。结果　冠心病组血流介导的肱动脉舒张和硝酸甘油所致的肱动脉舒张均低于对照组 [分别为 (2 6 1± 2 91) %比 (8 0 1± 4 72 ) %和 (17 2 2± 6 76 ) %比 (2 3 13± 8 6 1) % ,P均 <0 0 0 1]。多因素线性逐步回归分析显示 :血流介导的肱动脉舒张与血清HDL C水平呈正相关 (r=0 32 4,P =0 0 0 2 ) ,与血清总胆固醇、甘油三酯和低密度脂蛋白水平无关 ;硝酸甘油所致的肱动脉舒张也与上述血脂水平无关。根据血流介导的肱动脉舒张程度将两组受试者合并再分为A、B两组 ,A组肱动脉舒张≤ 4% ,B组肱动脉舒张 >4%。结果显示 ,A组HDL C水平明显低于B组 [(1 15± 0 2 6 )mmol/L对 (1 38± 0 5 0 )mmol/L ,P <0 0 1) ]。结论　冠心病患者内皮依赖性及非内皮依赖性的血管舒张功能均受损。HDL C对血管内皮依赖性舒张功能有保护作用 ,该作用可能与其抗动脉粥样硬化作用有关     

阿托伐他汀对冠心病患者的血管舒张功能的影响

目的观察阿托伐他汀对冠心病患者血管舒张功能的作用。方法将入选60例冠心病并高胆固醇血症患者随机分为阿托伐他汀治疗组(A组)和对照组(B组)。分别测定血清胆固醇、三酰甘油、低密度脂蛋白胆固醇和高密度脂蛋白胆固醇。并应用高分辨率超声技术,检测治疗前、后两组肱动脉血流介导和硝酸甘油介导的舒张功能。结果治疗前,冠心病并高胆固醇血症患者肱动脉血流介导和硝酸甘油介导的舒张功能均低于健康对照组(P<0.01)。经阿托伐他汀治疗6个月后A组血浆总胆固醇、三酰甘油和低密度脂蛋白胆固醇显著降低(P<0.01),高密度脂蛋白胆固醇显著升高(P<0.01)。随着血脂的改善,肱动脉内皮依赖性血管舒张功能显著提高(P<0.01),但硝酸甘油介导的血管舒张功能未见改善(P>0.05)。结论冠心病并高胆固醇血症患者存在内皮依赖性血管舒张功能障碍,经阿托伐他汀调脂治疗后,受损的内皮依赖性血管舒张功能得到明显改善。     

两种不同剂量辛伐他汀对冠心病患者血管内皮功能的影响

目的探讨辛伐他汀10 mg与20 mg不同剂量对冠心病患者血管内皮功能作用的影响。方法共入选66例冠心病患者,随机分为对照组、辛伐他汀10 mg组和辛伐他汀20 mg组,治疗8周。采用超声法检测血流介导的肱动脉内皮依赖性舒张功能,同时观察血脂水平的变化。结果辛伐他汀治疗8周后,10 mg和20 mg辛伐他汀呈剂量依赖性显著降低血总胆固醇和低密度脂蛋白胆固醇水平(总胆固醇分别降低18.3%和29.3%;低密度脂蛋白胆固醇分别降低25.3%和35.4%;P<0.05)。对照组治疗8周后血脂水平无明显变(P>0.05)。10 mg和20 mg辛伐他汀均可显著改善肱动脉内皮依赖性舒张功能(10 mg辛伐他汀组为3.51%±4.03%比7.46%±5.90%;20mg辛伐他汀组为3.89%±3.97%比7.98%±6.16%;P均<0.01)。但两组之间肱动脉内皮依赖性舒张功能的变化值比较差异无显著性(P>0.05),且肱动脉内皮依赖性舒张功能的改善与血总胆固醇和低密度脂蛋白胆固醇水平的降低不相关。对照组肱动脉内皮依赖性舒张功能虽有轻度增加,但无统计学意义。辛伐他汀治疗后肱动脉内径和肱动脉对硝酸甘油的反应均无显著改变。结论10 mg和20 mg辛伐他汀治疗8周后,可显著改善冠心病患者血管内皮功能,但该作用在这2种剂量之间无显著不同,可能独立于调脂作用之外。     

辛伐他汀对高脂血症患者内皮功能障碍的干预作用及其与碱性成纤维细胞生长因子的关系

目的 研究辛伐他汀对高脂血症患者血管内皮功能障碍的干预作用及其与血清碱性成纤维细胞生长因子的关系.方法 将54例高脂血症患者按血脂水平随机分为辛伐他汀组(28例,辛伐他汀20 mg/d,8周)和高.脂对照组(26例),另设正常对照组(29例,正常健康受试者).应用彩色多谱勒超声诊断仪测量受试者肱动脉血流介导的舒张功能,评价血管内皮功能的变化.应用酶联免疫吸附双抗体夹心法和硝酸酶还原法检测受试者血清碱性成纤维细胞生长因子和一氧化氮的含量,评价一氧化氮及碱性成纤维细胞生长因子与血管内皮功能障碍的关系.常规检测血清总胆固醇、甘油三酯、低密度脂蛋白及高密度脂蛋白的浓度.结果 8周后,辛伐他汀组与高脂对照组相比肱动脉血流介导的舒张功能明显改善(P<0.05),血清一氧化氮和血清碱性成纤维细胞生长因子含量升高(P<0.05),血清总胆固醇、甘油三酯和低密度脂蛋白浓度明显下降(P<0.01),而高密度脂蛋白浓度明显升高(P<0.01).结论 辛伐他汀可增加血清碱性成纤维细胞生长因子含量,提高一氧化氮含量,改善高脂血症患者血管内皮功能障碍,其作用机制与降低血清总胆固醇、甘油三酯和低密度脂蛋白的浓度有一定关系.     

高甘油三酯血症对血管内皮功能的影响

目的　观察高甘油三酯血症对血管内皮功能的影响。方法　对 30例高甘油三酯血症患者和 30例正常人 ,采用高分辨超声技术检测血流介导的和硝酸甘油介导的肱动脉舒张功能 ,并测定血浆内皮素和血脂。结果　 1.高甘油三酯血症组血流介导的肱动脉舒张较正常组明显减弱 [分别为 (2 7± 2 0 ) %和 (15 0± 8 0 ) % ,P <0 0 0 1],而两组对硝酸甘油的血管舒张反应无显著性差异 [分别为 (15 0± 5 0 ) %和 (16 8± 9 0 ) % ,P >0 0 5 ]。 2 高甘油三酯血症组血浆内皮素水平显著高于正常组 [分别为 (10 6 2 2± 19 16 ) μg/L和 (72 37± 14 0 6 ) μg/L ,P <0 0 0 1]。结论　高甘油三酯血症患者内皮依赖性血管舒张功能明显受损。血管内皮功能失调可能是高甘油三酯血症致动脉粥样硬化的一个重要机制。     

高甘油三酯血症对血管内皮功能的影响

目的　观察高甘油三酯血症对血管内皮功能的影响。方法　对 30名高甘油三酯血症患者和 30名正常人采用高分辨超声技术检测血流介导和硝酸甘油介导的肱动脉舒张功能 ,并测定血浆内皮素和血脂。结果　 (1)高甘油三酯血症患者血流介导的肱动脉舒张较正常组明显减弱 [分别为(2 7± 2 0 ) %和 (15 0± 8 0 ) % ,P <0 0 0 1],而两组对硝酸甘油的血管舒张反应无显著性差异 [分别为 (15 0± 5 0 ) %和 (16 8± 9 0 ) % ,P >0 0 5 ]。 (2 )高甘油三酯血症患者血浆内皮素水平 [(10 6 2 2± 19 16 ) μg/L]显著高于正常组 [(72 37± 14 0 6 ) μg/L](P <0 0 0 1)。 结论　高甘油三酯血症患者内皮依赖性血管舒张功能明显受损。血管内皮功能失调可能是高甘油三酯血症致动脉粥样硬化的一个重要机制。     

高甘油三酯血症对血管内皮功能的影响

目的观察高甘油三酯血症对血管内皮功能的影响.方法对30例高甘油三酯血症患者和30例正常人,采用高分辨超声技术检测血流介导的和硝酸甘油介导的肱动脉舒张功能,并测定血浆内皮素和血脂.结果 1.高甘油三酯血症组血流介导的肱动脉舒张较正常组明显减弱[分别为(2.7±2.0)%和(15.0±8.0)%,P<0.001],而两组对硝酸甘油的血管舒张反应无显著性差异[分别为(15.0±5.0)%和(16.8±9.0)%,P>0.05].2.高甘油三酯血症组血浆内皮素水平显著高于正常组[分别为(106.22±19.16)μg/L和(72.37±14.06)μg/L,P<0.001].结论高甘油三酯血症患者内皮依赖性血管舒张功能明显受损.血管内皮功能失调可能是高甘油三酯血症致动脉粥样硬化的一个重要机制.     

维生素C对高脂餐后内皮依赖性血管舒张功能的保护作用

目的探讨维生素C对高脂餐后内皮依赖性血管舒张功能变化的影响。方法74例冠心病患者被随机分为两组,分别在禁食12h后进食高脂餐与维生素C2g（A组,n＝37）或单纯的高脂餐（B组,n＝37）。分别采集餐前及餐后2、4、5、7h静脉血标本,用以测定血清甘油三酯(TG)、总胆固醇、低密度脂蛋白-胆固醇（LDL-C）、高密度脂蛋白-胆固醇（HDL-C）浓度。采用高分辨血管外超声法检测餐前及餐后4h肱动脉血流介导的内皮依赖性血管舒张功能和硝酸甘油介导的内皮非依赖性血管舒张功能。结果冠心病患者空腹状态的内皮依赖性血管舒张功能显著受损。服用维生素C2g（A组）餐后4h内皮依赖性血管舒张功能较餐前无显著变化［（3.63±0.59）%∶（4.51±0.49）%,P=0.064］;未服用维生素C2g（B组）餐后4h内皮依赖性血管舒张功能较餐前相比严重受损［（3.58±0.63）%∶（0.58±0.40）%,P<0.001］。高脂餐后硝酸甘油介导的内皮非依赖性血管舒张功能的变化无统计学意义［A组（19.48±1.38）%∶（20.25±1.21）%,P=0.498;B组（18.71±1.53）%∶（16.36±1.53）%,P=0.135］。两组受试者餐后2～7h血清TG浓度均显著升高。经相关分析结果显示B组受试者的餐后2h血清TG浓度增高值与餐后4h内皮依赖性血管舒张功能下降值显著正相关（r=0.395,P<0.02）。结论高脂餐后内皮依赖性血管舒张功能显著受损,大剂量维生素C对其有保护作用。     

女性甲减患者甲状腺素治疗改善内皮细胞依赖性血管舒张功能

目的　观察甲状腺功能减退症(甲减)患者甲状腺激素补充治疗后内皮依赖性血管舒张功能的变化。方法　选择初诊的女性临床甲减患者33例、亚临床甲减患者25例及正常健康女性25名。采用高分辨血管外超声法检测肱动脉血流介导的内皮依赖性血管舒张功能和硝酸甘油(GNT)介导的非内皮依赖性血管舒张功能。结果　(1)与对照组比较,临床甲减组和亚临床甲减组治疗前TSH、脂蛋白(a)〔L(a)〕、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL C)水平明显升高,血流介导的血管舒张功能降低(均<0. 05)。(2)与治疗前比较,临床甲减组和亚临床甲减组TSH、Lp(a)、LDL C、载脂蛋白B水平明显降低;血流介导的血管舒张功能明显升高(均P<0. 05)。(3)临床甲减组和亚临床甲减组治疗前后TSH、Lp(a)LDL C的变化与血流介导的血管舒张功能呈负相关(均P<0. 05)。结论　甲减患者内皮依赖性血管舒张功能降低,甲状腺激素补充治疗可改善内皮功能。     

氟伐他汀对血管内皮依赖性舒张功能的影响

目的:观察氟伐他汀对于血管内皮依赖性舒张功能的影响.方法:选取高胆固醇血症的患者35例作为试验组,正常对照组25例.试验组患者进行8周氟伐他汀40 mg/d,口服治疗.对35例高胆固醇血症患者采用彩色多普勒超声诊断仪测定其用药前以及用药8周后的反应性充血时和含服硝酸甘油后的肱动脉内径的变化;同时采用生化技术测定其血清一氧化氮(NO)及一氧化氮合酶(NOS)水平.结果:①高胆固醇血症患者的血管内皮依赖性舒张功能、血清NO和NOS水平较正常人明显降低(P＜0.01).②经过8周的氟伐他汀治疗后,试验组的血清甘油三酯、总胆固醇和低密度脂蛋白胆固醇显著降低,而高密度脂蛋白胆固醇水平升高(P＜0.01),血管内皮依赖性舒张功能以及血清NO及NOS水平也较治疗前显著提高.结论:氟伐他汀在降脂的同时可以显著改善高胆固醇血症患者的血管内皮依赖性舒张功能,其作用与其上调NOS的表达水平有关,从而提高了NO生成水平.     

Transient endothelial dysfunction following flow-mediated dilation assessment

Flow-mediated dilation (FMD) is a widely used tool to investigate endothelial function. However, FMD assessment may cause mechanical damage to the arterial endothelium. In this study we investigated the effect of FMD assessment on endothelial function. We studied 20 healthy subjects (26 ± 6 years; 12 males). FMD was assessed by measuring brachial artery dilation in response to hyperemia after 5 min of forearm cuff inflation. Subjects were studied on 2 subsequent days. On day 1 they underwent two consecutive FMD measures, with the second test (FMD2) performed 15 min after the first test (FMD1). On day 2, the subjects were randomized to receive either placebo (saline) or intravenous l-arginine (10 g in 20 min). At the end of the infusion, patients underwent two consecutive FMD measures following the same protocol as on day 1. Asymmetric dimethyl-arginine (ADMA) serum levels were assessed on day 2 before FMD1 and FMD2. On day 1, FMD2 was lower than FMD1 in both groups (placebo 6.47 ± 2.1 vs. 7.86 ± 1.8%, P < 0.01; arginine 6.13 ± 2.6 vs. 7.76 ± 2.7%, P < 0.01). On day 2, a significant reduction of FMD was observed during FMD2 compared to FMD1 in the placebo group (5.82 ± 1.7 vs. 7.44 ± 2.2%, P < 0.001), but not in the arginine group (7.19 ± 1.5 vs. 7.27 ± 1.5, P = 0.67). ADMA levels significantly increased compared to baseline after FMD1 (0.59 ± 0.12–0.91 ± 0.64 μmol/l, P = 0.036), with similar changes in the two groups. FMD assessment induces a significant impairment of endothelial function. An increase of endogenous NO synthesis inhibitors seems responsible for the phenomenon that is reversed by l-arginine administration.     

The antioxidant alpha-lipoic acid improves endothelial dysfunction induced by acute hyperglycaemia during OGTT in impaired glucose tolerance

Objective Impaired glucose tolerance (IGT) is considered a transitional phase in the development of type 2 diabetes, and is also independently associated with the occurrence of cardiovascular disease. Endothelial dysfunction (ED) represents a very early step in the development of atherosclerosis. The aim of the present study was to examine ED in the fasting state and after a glucose challenge as well as after administration of an antioxidant agent. Patients and methods The study subjects included 42 IGT patients and 26 healthy individuals (control group). The IGT patients were randomly divided into two groups, 21 in each group (the alpha‐lipoic acid group and the placebo group). In the alpha‐lipoic acid group, 300 mg of alpha‐lipoic acid was administrated before an oral glucose tolerance test (OGTT); in the placebo group, 250 ml of 0·9% sodium chloride was administrated before the OGTT. In addition, 250 ml of 0·9% sodium chloride was also administrated to the control subjects before the OGTT (control group), and then vascular function was examined in the fasting state and repeated 1 and 2 h after the glucose load. High‐resolution ultrasound was used to measure flow‐mediated endothelium‐dependent arterial dilation (FMD) and glyceryltrinitrate (GTN)‐induced endothelium‐independent arterial dilation. Results In the fasting state, and at 60 and 120 min, FMD in both the placebo and alpha‐lipoic acid groups was significantly lower than in the controls (P < 0·01). In the control group, FMD tended to decrease at 60 min after glucose loading and returned to the baseline levels at 120 min (P > 0·05). In the placebo group, FMD decreased significantly at 60 min after glucose loading (P < 0·01) and increased markedly from 60 to 120 min (P < 0·01). The alpha‐lipoic acid‐treated patients showed FMD values intermediate between the control subjects and the IGT patients treated with placebo, at both 60 and 120 min, and the differences were significant (P < 0·01). In multiple regression analysis, FMD was significantly correlated to fasting blood glucose (FBG), low density lipoprotein cholesterol (LDL‐C), lipoprotein (a) [Lp(a)], C‐reactive protein (CRP), thiobarbituric acid reactive substances (TBARS) and age in IGT patients at baseline (P < 0·01). Spearman's analysis showed a significant negative correlation between FMD and plasma glucose levels, and between FMD and TBARS during the OGTT in IGT patients (placebo group) (P < 0·01). There was also a significant correlation between FMD and plasma glucose levels, and between FMD and TBARS during the OGTT in IGT patients treated with alpha‐lipoic acid (P < 0·05), although the power of association decreased. Conclusion In subjects with IGT, FMD was impaired both in the fasting state and after a glucose challenge, probably through increased production of oxygen‐derived free radicals. The ED observed after a glucose challenge is related to the extent of hyperglycaemia and TBARS, and an antioxidant agent can improve the impairment of endothelial function induced by acute hyperglycaemia.     

Short‐Term Effect of Atorvastatin on Endothelial Function in Healthy Offspring of Parents with Type 2 Diabetes Mellitus

Endothelial function is impaired in healthy subjects at risk of type 2 diabetes mellitus (DM). We investigated whether endothelial dysfunction can be normalized by statin therapy in this potentially predisposed population. Flow‐mediated dilation (FMD) was measured in 56 first‐degree relatives (FDRs) (normotensive, normal glucose tolerance) and 20 age‐, sex‐, and BMI‐matched controls with no family history of DM. Other measurements included insulin resistance index using the homeostasis model of insulin resistance (HOMA_IR), plasma lipids, and markers of inflammation. The FDRs were then randomized and treated with atorvastatin (80 mg) or placebo daily in a 4‐week double‐blind, placebo‐controlled trial. The FDRs had significantly impaired FMD (4.4 ± 8.1% vs. 13.0 ± 4.2%; P < 0.001), higher HOMA_IR (1.72 ± 1.45 vs. 1.25 ± 0.43; P= 0.002), and elevated levels of plasma markers of inflammation—highly sensitive C‐reactive protein (hsCRP) (2.6 ± 3.8 mg/L vs. 0.7 ± 1.0 mg/L; P= 0.06), interleukin (IL)‐6 (0.07 ± 0.13 ng/mL vs. 0.03 ± 0.01 ng/mL; P < 0.001), and soluble intercellular adhesion molecule (sICAM) (267.7 ± 30.7 ng/mL vs. 238.2 ± 20.4 ng/mL; P < 0.001). FMD improved in the atorvastatin‐treated subjects when compared with the placebo‐treated subjects (atorvastatin, from 3.7 ± 8.5% to 9.8 ± 7.3%; placebo, from 3.9 ± 5.6% to 4.7 ± 4.2%; P= 0.001). There were also reductions in the levels of IL‐6 (0.08 ± 0.02 ng/mL vs. 0.04 ± 0.01 ng/mL; P < 0.001) and hsCRP (3.0 ± 3.9 mg/L vs. 1.0 ± 1.3 mg/L; P= 0.006). Our study suggests that treatment with atorvastatin may improve endothelial function and decrease levels of inflammatory markers in FDRs of type 2 DM patients.     

Loss of systemic endothelial function post-PCI

To investigate loss of systemic endothelial function post-PCI and evaluate the putative therapeutic effect of BNP. Loss of endothelial function (LEF) post-PCI may contribute to both acute and long-term complications. A protective effect of BNP on endothelium was suggested previously. Flow-mediated vasodilation (FMD) of the brachial artery, as well as plasma levels of endothelin, BNP, Pro BNP and corin were measured before and following routine PCI. 49 patients with normal baseline endothelial function were recruited. 30 patients developed LEF and were randomized to i.v. nesiritide (the commercially available recombinant form of human BNP) or saline infusion for 3 h. Patients who developed LEF post-PCI had reduced baseline plasma corin levels and their BNP/ProBNP ratio was reduced after the procedure. Nesiritide infusion significantly improved FMD both immediately (Nesiritide versus saline: 2.87±0.78% versus 0.51±0.25%, P=0.007) and 24 h after the treatment (2.52±0.69% versus 0.72±0.32%, P=0.025). The elevated plasma ET-1 was reduced by Nesiritide (0.38±0.11 fmol/ml 24 h post-PCI versus 0.16±0.02 fmol/ml 24 h post BNP, P=0.047), but remained unchanged in saline group (0.39±0.21 fmol/ml versus 0.42±0.23 fmol/ml, P=0.749). Systemic LEF post-PCI is a frequent event. It may be related to impaired cleavage of ProBNP to BNP. Short-term i.v. nesiritide improves systemic LEF post-PCI.     

Long‐term effects of weight loss with a very low carbohydrate and low fat diet on vascular function in overweight and obese patients

Abstract. Wycherley TP, Brinkworth GD, Keogh JB, Noakes M, Buckley JD, Clifton PM. (Commonwealth Scientific and Industrial Research Organization, Food and Nutritional Sciences; School of Molecular and Biomedical Science, University of Adelaide; and Nutritional Physiology Research Centre and Australian Technology Network Centre for Metabolic Fitness, Sansom Institute for Health Research, University of South Australia). Long‐term effects of weight loss with a very low carbohydrate and low fat diet on vascular function in overweight and obese patients. J Intern Med 2010; 267 : 452–461. Objective. To compare the effects of an energy reduced very low carbohydrate, high saturated fat diet (LC) and an isocaloric high carbohydrate, low fat diet (LF) on endothelial function after 12 months. Design and Subjects. Forty‐nine overweight or obese patients (age 50.0 ± 1.1 years, BMI 33.7 ± 0.6 kg m^?2) were randomized to either an energy restricted (～6–7 MJ), planned isocaloric LC or LF for 52 weeks. Body weight, endothelium‐derived factors, flow‐mediated dilatation (FMD), adiponectin, augmentation index (AIx) and pulse wave velocity (PWV) were assessed. All data are mean ± SEM. Results. Weight loss was similar in both groups (LC ?14.9 ± 2.1 kg, LF ?11.5 ± 1.5 kg; P = 0.20). There was a significant time × diet effect for FMD (P = 0.045); FMD decreased in LC (5.7 ± 0.7% to 3.7 ± 0.5%) but remained unchanged in LF (5.9 ± 0.5% to 5.5 ± 0.7%). PWV improved in both groups (LC ?1.4 ± 0.6 m s^?1, LF ?1.5 ± 0.6 m s^?1; P = 0.001 for time) with no diet effect (P = 0.80). AIx and VCAM‐1 did not change in either group. Adiponectin, eSelectin, tPA and PAI‐1 improved similarly in both groups (P < 0.01 for time). Conclusion. Both LC and LF hypoenergetic diets achieved similar reductions in body weight and were associated with improvements in PWV and a number of endothelium‐derived factors. However, the LC diet impaired FMD suggesting chronic consumption of a LC diet may have detrimental effects on endothelial function.     

Changes in endothelial function and its association with plasma osteoprotegerin in hypothyroidism with exercise-induced silent myocardial ischaemia

Objective Hypothyroidism is associated with an increased risk for cardiovascular disease. Exercise‐induced silent myocardial ischaemia (SI) is an early stage of coronary artery disease. Recently, many studies have shown that endothelial dysfunction is an early physiological event in atherosclerosis, and osteoprotegerin (OPG) acts as an important regulatory molecule in the vasculature. The aim of this study was to investigate the alteration of endothelial function and its association with plasma OPG in hypothyroidism with SI. Methods Forty‐eight female postmenopausal hypothyroid patients with normal rest electrocardiography (ECG) were selected. Of these, 19 cases had SI. Twenty healthy females without SI were selected as controls. High‐resolution ultrasound was used to measure brachial artery diameter at rest, after reactive hyperaemia and after sublingual glyceryltrinitrate (GTN). Plasma OPG concentration was measured in duplicate by a sandwich enzyme‐linked immunosorbent assay (ELISA). Results Flow‐mediated arterial dilation (FMD) in the total hypothyroid group, the hypothyroidism with SI group and the hypothyroidism without SI group was 3·51 ± 0·62%, 3·20 ± 0·54% and 3·72 ± 0·60%, respectively, significantly lower than that in the controls (5·08 ± 0·61%) (P < 0·01). Compared with the hypothyroidism without SI group, FMD in the hypothyroidism with SI group was significantly lower (P < 0·05). Plasma OPG levels in the total hypothyroid group, patients with SI and patients without SI were significantly higher than in the control group (P < 0·05). Compared with patients without SI, OPG levels were significantly higher in patients with SI (P < 0·05). On multiple regression analysis, low density lipoprotein cholesterol (LDL‐C), lipoprotein (a) [Lp(a)], C‐reactive protein (CRP), OPG, TSH, free T3 (FT3) and thyroid peroxidase antibody (TPO‐Ab) were found to be significant factors that were associated with FMD. Logistic analysis also showed that LDL‐C, TSH, OPG, CRP and FMD were independently and significantly associated with SI in hypothyroidism. Conclusion Impaired endothelial function and increased levels of OPG exist in hypothyroid patients, especially those with SI. These findings support the growing concept that endothelial dysfunction may be associated with vascular disease, and subsequently elevated plasma OPG may have a role in the development of vascular dysfunction in hypothyroid patients.     

Additive effect of homocysteine- and cholesterol-lowering therapy on endothelium-dependent vasodilation in patients with cardiovascular disease

Aim : Endothelial dysfunction is a marker for development and progression of atherosclerosis. Statin therapy improves endothelial function in cardiovascular patients by reducing LDL‐cholesterol and by pleiotropic effects. B‐group vitamin supplementation restores endothelial function mainly by reducing homocysteine‐induced oxidative stress. Thus, we evaluated the effect of rosuvastatin, B‐group vitamins and their combination on endothelial function in high‐risk cardiovascular patients. Methods : Thirty‐six patients with cardiovascular disease were randomly, double‐blinded assigned to either rosuvastatin 10 mg (group R, n = 18) or vitamin supplementation consisting of folic acid 1 mg, vitamin B12 0.4 mg, and B6 10 mg (group V, n = 18) for 6 weeks. After 6 weeks all patients received rosuvastatin and vitamin supplementation in combination for additional 6 weeks. Endothelial function was assessed by flow‐mediated vasodilation (FMD) at baseline and after 6‐ and 12‐week treatment. Results : At baseline, FMD, plasma lipids, vitamins, and homocysteine were comparable between both groups. After 6 weeks, FMD improved in both groups (from 4.4 ± 1.6 to 6.9 ± 1.4% group R, P= 0.0004 and from 4.9 ± 1.8 to 6.4 ± 1.8% group V, P= 0.0002). This improvement in FMD was mainly associated with a decrease of plasma lipids in group R and a decrease of homocysteine in group V. After 12 weeks, the combined therapy with rosuvastatin and vitamins further improved FMD to the normal range in 26/33 patients compared to 5/36 at baseline (P < 0.0001). Conclusions : In conclusion, both treatments, rosuvastatin and B‐group vitamin supplementation, improved endothelial function in high‐risk cardiovascular patients. The combination of both therapies had an additive effect on endothelial function suggesting different mechanisms of action.     

阿托伐他汀对不同血脂水平的高血压病患者血管内皮功能的影响

目的研究阿托伐他汀对正常血脂和高血脂的高血压病(EH)患者血管内皮功能的影响。方法采用双盲、随机、对照方法，将正常血脂(NC组)和高血脂(HC组)高血压病患者分为他汀治疗组(阿托伐他汀20mg／d，共8周，NC组，n=22；HC组，n=24)和未用药对照组(NC组n=21；HC组，n=24)；运用无创超声检查技术，观察用药前后颈动脉内-中膜厚度(IMT)及肱动脉内皮依赖性舒张功能(FMD)的变化，同时检测血清一氧化氮(NO)及内皮素-1(ET-1)的浓度水平。结果治疗前NC、HC各组IMT值和血清ET-1水平较健康对照组(n=40)明显升高(P＜0．01)，FMD值和NO水平却显著下降(P＜O．01)，IMT、FMD、NO与LDI-C存在着显著的相关性。治疗8周后，NC、HC各组IMT值和ET-1水平明显降低，FMD和NO水平显著上升。与对照组比较，他汀治疗组的IMT、ET-1降低更明显(P＜O．05)，FMD和NO升高更为显著(P＜O．05)。两他汀治疗组的血脂水平较治疗前均明显下降(P＜O．05，P＜O．01)。结论阿托伐他汀治疗正常血脂和高血脂的高血压病患者，可在有效调脂的同时，发挥其非调脂作用，逆转或延迟颈动脉IMT的进程，改善血管内皮功能。     

Hypothyroidism is associated with signs of endothelial dysfunction despite 1-year replacement therapy with levothyroxine

Objective Hypothyroidism is associated with elevated cardiovascular risk, not fully explained by classical risk factors. Instead, endothelial dysfunction may link hypothyroidism to atherosclerosis. The effect of levothyroxine substitution on endothelial function has been sparsely studied and the results are unclear. This study tested endothelial function as estimated by concomitant measurements of endothelial dependent vascular dilatory capacity and plasma concentration of von Willebrand factor antigen in patients with hypothyroidism and further examined the impact of subsequent levothyroxine substitution. Design and patients Sixteen consecutive patients (13 women, 3 men, aged 46 ± 11 years) with hypothyroidism were included and compared to 16 matched healthy controls (13 women, 3 men, aged 49 ± 11 years). Patients with hypothyroidism were reexamined after 3, 6 and 12 months of levothyroxine substitution. Measurements Dilatory responses of the brachial artery to post‐ischaemic increased blood flow (endothelium‐dependent flow‐associated dilatation) and to nitroglycerin (endothelium‐independent nitroglycerin induced dilatation) were measured by ultrasound. Plasma concentrations of von Willebrand factor antigen were measured by ELISA. Results Flow‐associated dilatation was impaired in patients with hypothyroidism as compared to controls (102·7 ± 3·6 vs. 105·6 ± 3·8%, P = 0·04) whereas no differences in plasma concentration of von Willebrand factor antigen were found. One year levothyroxine substitution did not improve flow‐associated dilatation and was associated with an increase of the plasma von Willebrand factor antigen concentration. Conclusions Hypothyroid patients are characterized by endothelial dysfunction sustained despite long‐term levothyroxine substitution and potentially increasing the risk of atherosclerosis. Different estimates of endothelial dysfunction seem unequally influenced by hypothyroidism.     

Adolescents with congenital adrenal hyperplasia because of 21-hydroxylase deficiency have vascular dysfunction

Context Patients with congenital adrenal hyperplasia (CAH) because of 21‐hydroxylase deficiency have multiple vascular risk factors. Young adults with CAH have increased intima media thickness, but there have been no studies of vascular function and structure in children with CAH. Objective To establish whether children with CAH have reduced vascular function and increased carotid intima media thickness (cIMT) when compared to healthy and obese children. Design and Patients Cross‐sectional study of 14 patients (14·8 years ± 3·2, seven boys) with CAH secondary to 21‐hydroxylase deficiency compared to 28 obese and 53 healthy controls. Measurements All subjects had assessment of endothelial function flow‐mediated dilatation, (FMD), smooth muscle function glyceryl tri‐nitrate dilatation (GTN) and cIMT. Anthropometric data, resting blood pressure and biochemical variables were also measured. Results Congenital adrenal hyperplasia subjects had significantly reduced FMD (4·5 ± 3·0%vs 7·5 ± 5·2%; P = 0·04) and GTN (17·2 ± 1·6%vs 28·4 ± 8·4%; P < 0·001) when compared to controls and the impairment was comparable to the obese cohort. There was no significant difference in cIMT between groups. CAH subjects had increased homoeostasis model of assessment‐insulin resistance [HOMA‐IR 2·5 (0·2–2·9) vs 1·8 (0·5–4·2); P = 0·04], waist‐to‐height ratio (0·47 ± 0·05 vs 0·44 ± 0·04; P = 0·02) and higher systolic blood pressure Z score (0·29 ± 0·9 vs?0·24 ± 0·64, P = 0·01) compared to healthy controls but not when compared to obese controls. Conclusions Subjects with CAH have evidence of vascular dysfunction by adolescence.