苯扎贝特联合降压治疗对高血压合并高甘油三酯血症患者内皮功能和血压的影响

目的用随机、对照的方法观察苯扎贝特联合降压治疗对高甘油三酯血症合并高血压患者内皮功能和血压的影响.方法 58例高甘油三酯血症伴原发性高血压患者随机分为苯扎贝特组(A组)和对照组(B组),通过治疗前后血压、血脂、血浆内皮素(endothelin, ET)、一氧化氮(nitric oxide, NO)、血栓烷A2(thromboxane A2, TXA2)、前列环素I2(PGI2)和降钙素基因相关肽(calcitonin gene-related peptide, CGRP)等指标的变化,来观察苯扎贝特对患者血管内皮功能和血压的影响.结果 A组在治疗后血甘油三酯、总胆固醇、低密度脂蛋白胆固醇水平明显降低,高密度脂蛋白胆固醇显著升高; NO显著升高, ET、TXA2/PGI2明显降低;而且A组舒张压降低较B组显著,并与血甘油三酯水平及内皮功能的变化有关.结论苯扎贝特可能通过调整血脂代谢紊乱,对患者的血管内皮功能有改善作用,并且在降压药物的基础上,可能对患者舒张压有额外降低作用.     

苯扎贝特联合降压治疗对高血压合并高甘油三酯血症患者胰岛素抵抗和血压的影响

用随机、对照的方法观察苯扎贝特联合降压治疗对高甘油三酯血症合并高血压患者胰岛素抵抗和血压的影响。择选58例高甘油三酯血症伴原发性高血压患者，随机分为苯扎贝特组和对照组，通过血压、血脂、空腹血糖、胰岛素浓度及胰岛素敏感性指数等的变化，来观察苯扎贝特对高甘油三酯血症合并高血压患者胰岛素抵抗和血压的影响。结果显示苯扎贝特组在治疗后舒张压降低较对照组显著；血甘油三酯、总胆固醇、低密度脂蛋白胆固醇水平明显降低，高密度脂蛋白胆固醇显著升高，空腹血糖及胰岛素浓度在治疗后明显降低，胰岛素敏感性指数明显升高。说明苯扎贝特可能通过改善血脂代谢紊乱，对患者的胰岛素抵抗有良性影响，并且可能在降压药物的基础上，对患者舒张压有额外降低作用。     

洛伐他汀和抗氧化剂对冠心病高胆固醇血症患者血管内皮功能的影响

目的　探讨洛伐他汀和抗氧化剂 (维生素 C、E、辅酶 Q1 0 )对冠心病高胆固醇血症患者血管内皮功能的影响。方法　 67例冠心病高胆固醇血症患者分别给予洛伐他汀 (A组 2 8例 ) ;洛伐他汀加抗氧化剂 (B组 1 8例 ) ;抗氧化剂 (C组 2 1例 )治疗 ,观察治疗前及治疗后 4w、8w TC、LDL- C、NO、ET、PGI2 及 TXA2 的变化。结果　治疗后 4 w、8w,A组 TC、LDL- C、TXA2 下降 ,ET减少 ,NO增加 ,PGI2 增加 (均 P<0 .0 5) ;B组 TC、LDL- C、TXA2 均下降 ,NO增加 (P<0 .0 5) ,PGI2 增加 ,其中 4w ET下降 (P<0 .0 5) ,8w ET下降 (P<0 .0 1 ) ;C组各项指标治疗前后比较均无显著差异。相关性检验显示 ,内皮功能的改善 (ET、TXA2 下降及 NO、PGI2 升高 )与血脂 (TC、LDL- C)下降无相关关系 (P>0 .0 5)。结论　洛伐他汀能够在降低血脂的同时改善内皮功能 ,加服抗氧化剂后此疗效更加显著 ,但内皮功能改善与血脂下降无关。     

苯那普利对高血压患者内皮功能的影响

目的 :探讨苯那普利对高血压患者内皮活性物质的影响。方法 :高血压患者 2 6例及正常对照组 2 4例 ,采用化学比色法测定NO、NOS和放射免疫法测定ET、Ang Ⅱ、TXA2 及PGI2 在血浆中的水平 ,并进行对比研究 ,对高血压组病人进行苯那普利治疗前后的对比研究。结果 :高血压组ET、Ang Ⅱ及TXA2 明显高于正常对照组 ,而NO、NOS及PGI2 明显低于对照组 ;苯那普利治疗组治疗后ET、Ang Ⅱ及TXA2 明显低于治疗前 ,NO、NOS及PGI2 明显高于治疗前 ;苯那普利治疗高血压有效率 84 6 %。结论 :高血压患者存在内皮功能障碍 ,EDCF分泌增多 ,EDRF分泌减少 ,苯那普利可升高EDRF ,减少EDCF ,对内皮功能有恢复作用。     

苯扎贝特对中老年高血压代谢综合征患者的影响

中国综合临床,2006,22:769-770该文探讨苯扎贝特对中老年高血压代谢综合征患者各代谢因素的影响。方法:将中老年高血压代谢综合征患者55例分为2组:苯扎贝特组28例给予缓释硝苯地平、苯扎贝特并饮食控制;对照组27例给予缓释硝苯地平、安慰剂并饮食控制。观察治疗前后血压、体质指数、血脂、空腹血糖、胰岛素、胰岛素抵抗指数及尿酸水平等变化。结果:2组血压水平均有明显下降,苯扎贝特组治疗后舒张压降低较对照组显著(P<0·05);苯扎贝特组血三酰甘油、总胆固醇、低密度脂蛋白胆固醇水平明显降低(P<0·05或0·01),高密度脂蛋白胆固醇显著升高(…     

缬沙坦的降压疗效及对患者血管内皮功能的影响

目的 探讨缬沙坦的降压疗效和对血管内皮功能的影响。方法 对60例高血压病患者分别应用缬沙坦和非洛地平治疗。记录每日血压和24h动态血压变化。取静脉血测定治疗前后血浆一氧化氮(NO)、前列环素(PGI)、内皮素(ET)、血管紧张素Ⅱ(AngⅡ)和血尿酸(BUA)水平。结果 缬沙坦的降压疗效明显，但同非洛地平相比较，两者无显著性差异(P＞0．05)；缬沙坦组血浆NO、PGI、AngⅡ是升高的，ET、BUA是降低的，副作用较轻。结论 缬沙坦是一种安全有效的降压药物，同时可以改善高血压患者的血管内皮功能。     

苯扎贝特治疗高三酰甘油血症的疗效观察

目的探讨苯扎贝特治疗高三酰甘油血症的疗效及安全性。方法连续入选门诊及住院高三酰甘油血症患者324例,采用随机双盲法分为苯扎贝特组和空白对照组,每组各162例,分别口服苯扎贝特0.2 g,3次/d和淀粉空白片0.2 g,3次/d,治疗1～3个月。结果苯扎贝特组治疗1个月后,血三酰甘油较治疗前下降了42.5%,总胆固醇下降了14.9%,高密度脂蛋白胆固醇升高了31.2%,低密度脂蛋白胆固醇下降了27.0%,餐后4 h三酰甘油下降了38.5%(均为P<0.01);而对照组治疗前后上述各项指标差异均无统计学意义(均为P>0.05)。治疗3个月后,苯扎贝特组患者血脂的达标率较治疗1个月后进一步提高。治疗过程中,苯扎贝特组患者的血压、血糖未见升高。结论苯扎贝特具有改善血脂的作用,尚不升高血压、血糖,有较好的安全性。     

非诺贝特对高三酰甘油血症患者血压、肱动脉舒张值的影响

目的 观察非诺贝特联合降压治疗对高血压合并高三酰甘油血症患者血压、血流介导的肱动脉_舒张值的影响.方法 62例合并高三酰甘油血症的原发性高血压患者随机分为调脂饮食加坎地沙坦加非诺贝特组(A组),调脂饮食加坎地沙坦加安慰剂组(B组).观察两组血压及血流介导的肱动脉舒张值的变化.结果 两组治疗后收缩压和舒张压均显著下降(P<0.01),A组较B组能更显著降低收缩压和舒张压(P<0.01).A组能显著降低总胆固醇、三酰甘油及低密度脂蛋白胆固醇水平,增加高密度脂蛋白胆固醇水平(P<0.01),而B组在治疗前后脂质谱无显著改善(P>0.05).两组治疗后血流介导的肱动脉舒张值明显增加(P<0.01),A组较B组能更显著增加血流介导的肱动脉舒张值(P<0.01).结论 非诺贝特可能通过改善血脂代谢紊乱,在降压药物的基础上,进一步改善患者的血管内皮功能,并且对患者血压有协同降低作用.     

冠心病患者血管内皮细胞功能的变化

目的　探讨血管内皮细胞功能障碍与冠心病 (CHD)的关系。方法　采用二维超声检测 70例CHD患者肱动脉血管内径 (内皮依赖性和内皮非依赖性舒缩功能 ) ,同时采用生化比色法测定CHD患者血浆一氧化氮 (NO) ,用放射免疫法测定血浆内皮素 (ET)、前列腺素 (PGI2 )、血栓素A2 (TXA2 )、肿瘤坏死因子 (TNF)、心钠素 (ANP)及降钙素基因相关肽 (CGRP)浓度 ,并以 2 0例健康人为对照组。结果　CHD组内皮依赖性血管舒缩功能与对照组比较明显降低 ,内皮非依赖性血管舒缩功能与对照组比较差异无显著性意义 ;CHD组与对照组比较 ,血浆平均ET、TXA2 、TNF显著升高 ,而血浆NO、PGI2 、ANP、CGRP水平显著降低。结论　内皮细胞功能障碍及其内皮源性血管活性物质和影响内皮功能的血管活性物质的失衡 ,在CHD的发病机制中起重要作用     

螺内酯对冠心病患者内皮细胞功能的影响

目的　本实验旨在探讨螺内酯对冠心病患者内皮细胞功能的影响。方法　选择 5 0例冠心病患者作为实验组 ,5 0例健康者作为对照组 ,给药前先测定实验组和对照组的内皮素 (ET)、血栓素 A2 (TXA2 )、一氧化氮 (NO)、前列环素 (PGI2 ) ,再予以实验组螺内酯 2 0 m g/ d,3个月后再测定实验组的 ET、TXA2 、NO、PGI2 并进行比较。结果　给药前实验组的 ET、TXA2 水平较对照组高 ,NO、PGI2 水平较对照组低 ;给药后 NO、PGI2 水平较给药前高 ,ET、TXA2 较给药前低。结论　螺内酯可以有效地改善血管内皮细胞功能 ,对逆转冠心病患者内皮细胞功能紊乱起着重要的作用。     

Bezafibrate reduces heart rate and blood pressure in patients with hypertriglyceridemia

OBJECTIVE: In hypertriglyceridemic patients, hypertension occurs frequently and may be associated with hyperinsulinemia and elevated plasma levels of free fatty acids (FFA). Besides the lipid-lowering effects, fibrates have been shown to reduce blood pressure in hypertensive patients. The present study was undertaken to investigate the effects of bezafibrate on hemodynamics in relation to insulin, FFA, sympathetic activity, renal sodium absorption, cyclic-GMP (cGMP) and endothelin-1 in hypertriglyceridemic patients. SUBJECTS AND METHODS: Hypertriglyceridemic patients (17) were randomized to receive in a double-blind placebo-controlled study bezafibrate or placebo for 6 weeks. At the end of both treatment periods, blood pressure and heart rate were measured automatically. Plasma insulin, FFA, aldosterone, catecholamines, cGMP, endothelin-1 levels and 24 h urine catecholamines and sodium excretion were assessed. RESULTS: Bezafibrate therapy decreased serum triglycerides (-65%, P < 0.001) and hemodynamic parameters: heart rate decreased from 69 to 66/min (P = 0.009), systolic blood pressure from 137 to 132 mmHg (P = 0.01), diastolic blood pressure from 81 to 79 mmHg (P = 0.07) and mean blood pressure from 102 to 99 mmHg (P = 0.06). Bezafibrate therapy reduced FFA and insulin (-55 and -57% respectively, both P < 0.001), while sympathetic activity and renal sodium absorption were not affected. cGMP increased (+17%, P = 0.008), whereas endothelin-1 levels tended to decrease upon bezafibrate therapy (-10%, P = 0.077) CONCLUSION: Bezafibrate reduces heart rate, blood pressure, insulin and FFA in hypertriglyceridemic patients. The hemodynamic effects cannot be attributed to changes in sympathetic activity or renal sodium absorption. Instead, based on the increase in plasma cGMP levels, the bezafibrate-induced hemodynamic effects are most likely to be caused by bezafibrate-induced improvement of endothelial function.     

Effect of nifedipine on adiponectin in hypertensive patients with type 2 diabetes mellitus

Nifedipine, a dihydropyridine calcium antagonist, improves endothelial function in patients with hypercholesterolaemia by enhancing nitric oxide (NO) activity, and increases endothelial NO bioavailability by antioxidant mechanisms. We administered a long-acting nifedipine formulation (controlled release (CR) nifedipine: 20 mg/day) to hypertensive patients for 6 months. There were no other changes of drug treatment during therapy with CR nifedipine. Clinical and biochemical data obtained before and after CR nifedipine administration were compared. All markers were measured by enzyme-linked immunosorbant assay. The levels of soluble markers (soluble CD40 ligand, soluble P-selectin, and soluble E-selectin), microparticles (MP) (platelet-derived MP, monocyte-derived MP, and endothelial cell-derived MP), and adiponectin differed between the control group and the hypertension group. The levels of these markers were also different in hypertensive patients with and without type 2 diabetes compared with the control group. In the hypertensive patients with type 2 diabetes, all markers except adiponectin decreased significantly after 3 months of CR nifedipine treatment. In contrast, markers were unchanged in the hypertensive patients without type 2 diabetes. Adiponectin was increased after 6 months of CR nifedipine treatment in hypertensive patients with type 2 diabetes. The effects of CR nifedipine on platelet/monocyte activation and adiponectin levels demonstrated in the present study indicate the potential effectiveness of calcium antagonist therapy for hypertensive patients with type 2 diabetes.     

Nifedipine improves endothelial function: role of endothelial progenitor cells

Nifedipine has been shown to improve endothelial function. Recent studies have indicated that endothelial function is correlated with the number of circulating endothelial progenitor cells (EPCs), but it is unclear whether nifedipine affects the number and function of EPCs. The aims of this study were to determine the effects of nifedipine on the number and function of EPCs and to investigate the relationship between improvement of endothelial function and EPC numbers in patients with hypertension. Stage 1 hypertensive men (n=37) were randomly divided into the nifedipine group and the control untreated group. The nifedipine group was administered slow-release nifedipine (20 mg) once daily. At baseline and after 4 weeks, flow-mediated dilation, blood pressure, biochemical data, and number of circulating CD34+CD133+ progenitor cells and EPCs were measured. The direct effects of nifedipine on EPC number and function were assessed in vitro. In the nifedipine group, flow-mediated dilation and the numbers of circulating CD34+CD133+ progenitor cells and EPCs were increased, along with a decrease of serum malondialdehyde low-density lipoprotein. The improvement of flow-mediated dilation by nifedipine was correlated with the increase of circulating CD34+CD133+ progenitor cells. Nifedipine also improved angiogenesis-related functions of EPCs (differentiation, migration, and resistance to oxidative stress) in vitro. Thus, nifedipine improved endothelial function and EPC function in stage 1 hypertensive subjects. The latter action may be mediated by reduction of oxidative stress and suppression of EPC apoptosis. These results demonstrate that nifedipine preserves endothelial integrity in patients with hypertension, at least partly, by enhancing EPC numbers and activity.     

A comparison of long acting nifedipine and enalapril in elderly hypertensives: a randomised, single-blind, cross-over study

The effects of nifedipine and enalapril on blood pressure (BP), heart rate, plasma and urine electrolyte, plasma renin activity (PRA), aldosterone and catecholamines, were studied in ten elderly hypertensive subjects in a randomised, single-blind, cross-over trial. Both nifedipine and enalapril were effective in lowering supine and erect systolic and diastolic BP, with nifedipine causing a significant (P less than 0.05) rise in heart rate. Arterial pressure rose to pre-treatment levels on withdrawal of both drugs. Plasma glucose fell significantly (P less than 0.02) on enalapril therapy, whilst no other biochemical changes were observed. PRA, aldosterone and adrenaline rose on nifedipine therapy whereas PRA showed a greater rise on enalapril with a fall in plasma aldosterone and no change in plasma adrenaline. Plasma noradrenaline was not altered by either agent. Unacceptable side effects occurred in patients taking nifedipine resulting in discontinuation of therapy in 2 patients and death in another. Nifedipine or enalapril monotherapy is effective in lowering BP in the elderly hypertensives. Although more experience is needed, the side effect profile of both agents especially enalapril, appears satisfactory.     

等长运动对原发性高血压患者交感肾上腺素能系统的影响

目的通过等长(握力)运动前后原发性高血压患者心率、血压及血浆儿茶酚胺水平的变化,探讨等长运动对原发性高血压患者交感肾上腺素能系统的影响.方法分别观察38例原发性高血压患者(高血压组)及40例健康对照者(对照组)等长运动前后心率、血压及血浆儿茶酚胺(去甲肾上腺素、肾上腺素)水平;其中高血压组经硝苯地平治疗4周,再次进行等长运动试验.结果两组试验对象在等长运动后,心率、血压及血浆儿茶酚胺水平的增加较运动前均有非常显著性差异(P＜0.01).运动后高血压组的血压及血浆儿茶酚胺水平治疗后较治疗前升高显著,有非常显著性差异(P＜0.01).结论等长运动对原发性高血压患者交感肾上腺素能系统有激活作用;经硝苯地平治疗后血压虽有下降,但患者血浆儿茶酚胺水平却较治疗前显著升高,提示交感肾上腺素能系统的激活更为明显.     

Effects of bezafibrate on insulin secretion and peripheral insulin sensitivity in hyperlipidemic patients with and without diabetes

Although it has been reported that bezafibrate influences carbohydrate metabolism, this possibility has never been properly evaluated in a controlled clinical trial. In this study we attempted to evaluate the effects of bezafibrate on plasma lipoproteins, glucose tolerance, insulin secretion and peripheral insulin sensitivity in a group of hypertriglyceridemic patients with and without diabetes. Sixteen hyperlipidemic patients (10 males and 6 females) participated in the study. Eight had type IIB and 8 type IV hyperlipoproteinemia; 6 of them also had non-insulin dependent diabetes mellitus. The study was performed according to a double blind, crossover design: after 1 month wash-out period in which patients were on diet alone, they underwent, in a random order, a period of placebo therapy and another period in which they received a single daily dose of a long-acting bezafibrate preparation (400 mg) administered in the evening. Each treatment lasted 2 months. Total plasma and VLDL triglyceride concentrations were consistently reduced by bezafibrate (-46%, P less than 0.001; and -50%, P less than 0.001). Total and VLDL-cholesterol were also reduced by bezafibrate. The effects of bezafibrate on lipoproteins were similar in diabetic and non-diabetic subjects. Bezafibrate treatment did not influence fasting blood glucose concentration, glucose tolerance, peripheral insulin sensitivity or insulin secretion. In conclusion, the results of this controlled trial clearly indicate that bezafibrate can be successfully employed to lower plasma lipid levels in patients with non-insulin dependent diabetes mellitus and hyperlipidemia.     

Comparison about the efficacy and tolerability between simvastatin and bezafibrate in the treatment of hypercholesterolemia]

Simvastatin and bezafibrate actions on blood lipids and their side effects were compared in a double-blind trial involving 24 adults with severe type IIa or IIb primary hypercholesterolemia (mean plasma cholesterol = 4.35 g/l). During a 12-week period, the patients received either bezafibrate, 600 mg 3 times a day, or simvastatin, 10 or 20 mg once a day, with a doubling of the dosage at week 6 if the LDL-cholesterol level remained above 1.40 g/l. Simvastatin significantly reduced LDL-cholesterol by -39.5% (p less than 0.001), total cholesterol by 33.9% (p less than 0.005) and apoprotein B by -28% (p less than 0.001). Bezafibrate significantly reduced LDL-cholesterol (-19.8%, p less than 0.001) and total cholesterol (-17.5%, p less than 0.002), but not apoprotein B. Bezafibrate also reduced triglycerides by -26.6% and raised HDL-cholesterol by +27.6%. Simvastatin was more effective than bezafibrate in lowering LDL-cholesterol (p less than 0.002), total cholesterol (p less than 0.005) and apoprotein B (p less than 0.05). Tolerance of both drugs was considered excellent.     

The combination of vitamin C and grape-seed polyphenols increases blood pressure: a randomized, double-blind, placebo-controlled trial

BACKGROUND: There is growing evidence that oxidative stress contributes to the pathogenesis of hypertension and endothelial dysfunction. Thus, dietary antioxidants may beneficially influence blood pressure (BP) and endothelial function by reducing oxidative stress. OBJECTIVE: To determine if vitamin C and polyphenols, alone or in combination, can lower BP, improve endothelial function and reduce oxidative stress in hypertensive individuals. DESIGN: A total of 69 treated hypertensive individuals with a mean 24-h ambulatory systolic blood pressure > or = 125 mmHg participated in a randomized, double-blind, placebo-controlled, factorial trial. Following a 3-week washout, participants received 500 mg/day vitamin C, 1000 mg/day grape-seed polyphenols, both vitamin C and polyphenols, or neither for 6 weeks. At baseline and post-intervention, 24-h ambulatory BP, ultrasound-assessed endothelium-dependent and -independent vasodilation of the brachial artery, and markers of oxidative damage, (plasma and urinary F2-isoprostanes, oxidized low-density lipoproteins and plasma tocopherols), were measured. RESULTS: A significant interaction between grape-seed and vitamin C treatments for effects on BP was observed. Vitamin C alone reduced systolic BP versus placebo (-1.8 +/- 0.8 mmHg, P = 0.03), while polyphenols did not (-1.3 +/- 0.8 mmHg, P = 0.12). However, treatment with the combination of vitamin C and polyphenols increased systolic BP (4.8 +/- 0.9 mmHg versus placebo; 6.6 +/- 0.8 mmHg versus vitamin C; 6.1 +/- 0.9 mmHg versus polyphenols mmHg, each P < 0.0001) and diastolic BP (2.7 +/- 0.6 mmHg, P < 0.0001 versus placebo; 1.5 +/- 0.6 mmHg, P = 0.016 versus vitamin C; 3.2 +/- 0.7 mmHg, P < 0.0001 versus polyphenols). Endothelium-dependent and -independent vasodilation, and markers of oxidative damage were not significantly altered. CONCLUSION: Although the mechanism remains to be elucidated, these results suggest caution for hypertensive subjects taking supplements containing combinations of vitamin C and polyphenols.     

Normal oxidative stress and enhanced lipoprotein resistance to in vitro oxidation in hypertriglyceridemia: effects of bezafibrate therapy

Although there is evidence that hyperlipidemia and predominance of small dense low density lipoproteins (LDLs) are associated with increased oxidative stress, the oxidation status in patients with hypertriglyceridemia (HTG) has not been studied in detail. Therefore, we studied urinary levels of F(2)-isoprostanes (8-isoprostaglandin F(2alpha) and 2,3-dinor-5,6-dihydro-8-isoprostaglandin F(2alpha)) and susceptibility of very low density lipoproteins (VLDLs) and LDLs to oxidation ex vivo in 18 patients with endogenous HTG and 20 matched control subjects. In addition, the effects of 6 weeks of bezafibrate therapy were assessed in a double-blind, placebo-controlled, crossover trial. Urinary levels of F(2)-isoprostanes were similar in the HTG and normolipidemic group. Bezafibrate caused an increase in 8-isoprostaglandin F(2alpha) (762+/-313 versus 552+/-245 ng/24 h for bezafibrate and placebo therapy, respectively; P=0.03), whereas 2,3-dinor-5, 6-dihydro-8-isoprostaglandin F(2alpha) levels tended to be increased (1714+/-761 versus 1475+/-606 ng/24 h for bezafibrate and placebo therapy, respectively; P=0.11). VLDLs and LDLs were more resistant to copper-induced oxidation in patients with HTG than in control subjects. Bezafibrate reversed the oxidation resistance to the normal range. In conclusion, these results indicate the following: (1) HTG is associated with normal in vivo oxidative stress and enhanced ex vivo resistance of lipoproteins to oxidation. (2) Bezafibrate reduces the resistance of lipoproteins to copper-induced oxidation and enhances oxidative stress in HTG patients.