【作者】 李岩；

【导师】 马淑梅；

【作者基本信息】 中国医科大学 ， 内科学， 2008， 硕士

【摘要】 前言近年来,高血压的发病率在我国有持续上升的趋势,2005年中国心血管疾病报告显示我国大约有1.6亿高血压患者。高血压通过危害心、脑、肾、眼及下肢等器官病变而引起严重的并发症,从而危害人类的健康。高血压本身及各种并发症已给社会、家庭和个人造成了严重的危害和沉重的经济负担。为了改善高血压病人的预后,高血压患者的降压治疗不仅力求将血压控制在正常水平,同时需要逆转动脉弹性减退及内皮功能障碍等亚临床血管病变,这就需要评估降压药物是否对动脉弹性具有改善功能,以指导医生合理用药。自动测量臂踝脉搏波传导速度（brachial-ankle pulse wave velocity,baPWV）方法简便易行,重复性好,是无创性检查中能充分反应大动脉弹性的良好指标。国际上关于药物降压治疗降低baPWV的研究多为小样本、短期的随访研究,结果表明血管紧张素Ⅱ受体拮抗剂（ARB）、血管紧张素转换酶抑制剂（ACEI）和钙通道阻滞剂（CCB）均可不同程度地改善动脉僵硬度。国内在baPWV方面的研究较少,而对于测定降压治疗前后高血压患者baPWV变化的研究更是少有报道,本研究通过测定原发性高血压病人应用ACEI（培哚普利）、CCB（氨氯地平）、ARB（替米沙坦）降压前后baPWV的变化,比较三种降压药在改善高血压患者动脉弹性功能方面的差异,随访在血压降至正常并平稳后继续降压治疗是否对于动脉弹性仍然存在持续的改善作用。资料与方法选择原发性高血压病患者112例。随机分成三个治疗组:ACEI组、CCB组、ARB组,每个病人于早晨一次服用单一降压药物。所有入选对象在首次服药以后就定期进行血清生化试验和尿分析,定期测量血压。在开始时和服药一、三个月后应用科林波形分析仪PWV/ABI型仪器（BP-203RPE,日本科林公司）测量患者的baPWV。统计学分析:应用SPSS13.0软件进行统计学分析。数据以平均值±标准差表示。治疗前后结果比较采用配对t检验。三组间比较采用方差分析。实验结果1、所有入选对象被随机分配到ACEI组、CCB组、ARB组,最终每组入选34人,各组入选对象间在年龄、性别、吸烟人数、体重指数（BMI）、心率（HR）、收缩压（SBP）、舒张压（DBP）、脉压差（PP）、踝臂指数（ABI）、baPWV基线特征上无统计学差异（P＞0.05）。2、降压治疗后SBP、DBP、PP、HR变化降压治疗一个月及三个月后所有三组的SBP、DBP、PP均较治疗前明显降低（P＜0.001）;HR则未见明显变化（P＞0.05）。3、降压治疗前后baPWV测量值baPWV在三组经降压治疗后均有所下降,治疗一个月后与治疗前比较P＜0.001;治疗三个月后与治疗前比较P＜0.001;治疗三个月后与治疗一个月后比较ACEI组和ARB组P＜0.01,CCB组P＜0.001。4、降压治疗前后baPWV变化值降压治疗一个月后三组的baPWV变化（△baPWV1）及降压治疗三个月后三组的baPWV变化（△baPWV₃）均在ARB组最大（降压治疗一个月、三个月后分别为227.03±194.68 cm/s、292.71±242.56 cm/s）,其次为CCB组（降压治疗一个月、三个月后分别为132.76±147.72 cm/s、220.53±196.15 cm/s）,ACEI组最小（降压治疗一个月、三个月后分别为102.27±150.72 cm/s、156.50±235.17 cm/s）,在三组间比较有统计学差异（降压治疗一个月后P＜0.01和降压治疗三个月后P＜0.05）。降压治疗三个月后与降压治疗一个月后比三组baPWV均有进一步的下降（P＜0.01）。讨论目前,在全球心血管疾病的死亡率仅次于肿瘤疾病,高血压是心血管疾病的主要危险因素,在全世界日益成为主要危害健康的问题。降压治疗是控制高血压的重要手段,即使降压达到治疗目标水平,并不能使心血管疾病的危险性降至血压正常人群的水平,尤其是冠心病事件。其原因是因为心脏和血管结构的功能障碍早于高血压本身的进展,从而导致心血管事件的发生,所以对高血压患者的治疗不仅力求将血压控制在正常水平,同时需要逆转动脉弹性减退及内皮功能障碍等亚临床血管病变。为了改善高血压病人的预后,不仅要降低血压,也要降低动脉僵硬度。这就需要一个简单的指示器,能够评估药物是否对动脉僵硬度具有改善功能,以指导医生更加合理的用药。自动测量臂踝脉搏波传导速度应用震荡法测量仪器测量,是无创性反应大动脉弹性的良好指标。多项研究表明了baPWV的有效性和可重复性,而且这种简便的测量baPWV的方法与有创导管法获得的大动脉PWV、传统张力法测量的PWV良好相关,具有大范围筛查的价值。临床药物研究表明,不同的降压药物将血压降至同一水平时,对动脉僵硬性的改变不同。baPWV的测定可以帮助我们评估降压药物在改善动脉功能方面的作用,指导临床医师合理用药。目前,国际上关于药物降压治疗降低baPWV,从而反映降压治疗改善动脉僵硬度的研究多为小样本,短期随访研究,结果表明ARB、ACEI、CCB均可改善动脉僵硬度。国内在baPWV方面的研究较少,而对于测定ARB、ACEI、CCB降压治疗前后高血压病患者baPWV变化的研究更是少有报道,本研究通过测定应用培哚普利、氨氯地平、替米沙坦降压前后患者baPWV的变化,评价三种降压药对于高血压患者动脉弹性功能的改善作用。结果提示培哚普利、氨氯地平、替米沙坦均可显著降低SBP、DBP、PP,而患者HR在降压前后无明显变化;降压前后SBP、DBP、PP、HR变化在三组间比较无统计学差异。baPWV在三组高血压患者中经降压治疗后均有所下降,其中ARB组下降最为明显,其次为CCB组,ACEI组下降最少。降压治疗后SBP、DBP、PP、HR变化在三组间比较无统计学差异,而baPWV下降在ARB组最为明显可以提示我们替米沙坦可能存在降压之外的对于动脉弹性的改善作用。降压治疗一个月后及三个月后所有三组的baPWV均明显降低。降压治疗一月后baPWV变化及降压治疗三月后baPWV变化均在ARB组最大,其次为CCB组,ACEI组最小,在三组间比较有统计学差异（降压治疗一月后P＜0.01和降压治疗三月后P＜0.05）,提示我们对于轻中度高血压患者血压降至正常一个月及三个月时,改善动脉弹性的作用替米沙坦＞氨氯地平＞培哚普利。降压治疗三月后与降压治疗一月后比baPWV均有进一步的下降,在三组均有统计学差异（P＜0.05）。结论1、本研究结果提示应用培哚普利、氨氯地平、替米沙坦降压具有改善高血压患者动脉弹性功能的作用。2、降压治疗一个月及三个月时,替米沙坦改善动脉弹性的作用最为明显。3、血压降至正常并平稳后继续应用培哚普利、氨氯地平、替米沙坦降压治疗对于动脉弹性仍然存在持续的改善作用。更多还原

【Abstract】 PrefaceIn recent years, the morbidity of hypertension keeps increasing in China. There are approximately 1,6 billion peoples suffering from hypertension. High blood pressure could cause pathological changes in blood vessel and further endanger organs like heart, brain, kidney or eye, etc., to show serious complications.To improve the prognosis of patients with high blood pressure, the treatment of hypertension should not just control the blood pressure within normal ranges, but also include reversing the subclinical pathological changes like the reduced flexibility of artery and the functional disturbance of endodermis. Therefore, physicians should also evaluate whether a certain types of medicine could improve the flexibility of artery in order to make proper choice of different medicine.Automatic measurement of the brachial-ankle pulse wave velocity (baPWV), which is a good index of woundless reversion of the flexibility of major artery, is easy to do and duplicate. Previous investigation of reducing baPWV are done in small numbers of samples with short-term follow-up. Those studies showed that the angiotensin-converting enzyme inhibitor (ACEI), calcium channel blocker (CCB) and antgiotensin-receptor blocker (ARB) could improve arterial stiffness in patients with hypertension. In China, there are limited amount of studies using baPWV as a clinical index to evalutate the treatment effect of hypertension. Here, by comparing the changes of baPWV in patients treated with ACEI, CCB and ARB, we investigate the effect of those three medicines in improving the artery flexibility in patients with hypertension. Our follow-up visit also studies whether continued controlling of blood pressure will improve the flexibility of artery.Meterials and methodFor this study, we included 112 patients with primary hypertension. Patients were randomly assigned to three groups. Three groups were treated with either ACEI, CCB or ARB, once in the morning. All patients will receive periodic biochemical anaysis of serum, and exam of urine samples. baPWV was measured before the treatment, one-month and three-month after the treatment by PWV/ABI type instrument (form PWV/ABI; Colin, Co., Ltd., Komaki, Japan). Statistical analysis was determined by SPSS 13.0. Data were expressed as mean plus or minus one SD. Significant differences between pre- and post-treated were determined by paired-samples t-test. Difference among three groups were determined by one-wayanalysis of variance (ANOVA).Results1. Subjects were randomly assigned to one of three groups for treatment with the follow drugs: ACEI group, CCB group or ARB group. There were no statistically significant differences among the three treatment groups in their background factors such as age, sex, baPWV, ABI, ambulatory BP, heart rate, body mass index (BMI), or smoking habit.2. SBP, DBP and PP were significantly decreased in all three groups (P<0.001) . There were no significant changes in HR in all three groups (P>0.05) .3. BaPWV was significantly decreased in the ACEI, CCB, ARB groups. Compare the baPWV one-month after the treatment to before the treatment P<0.001; Compare the baPWV three-month after the treatment to before the treatment P<0.001; Compare the baPWV three-month to one-month after the treatment ACEI group and ARB group P<0.01,CCB group P<0.001.4. BaPWV was significantly decreased in all three groups in one or three months. The changes of baPWV in one or three months were significantly more in the ARB group than in the ACEI and CCB groups (1 months p<0.01 3 months p<0.05). The change of baPWV was significantly greater in three months than in one monthin in all three grops (p<0.01).DiscussionHypertension is one of the main risk factors for cardiovascular diseases. Hypertension has attracted more and more attention globally. Mounting evidences indicate that blood pressure must be reduced to below target levels, which vary according to the presence or absence of risk factors and complications. Since the anti-hypertensive therapy has the objective of preventing cardiovascular complications, the organ protective effect of anti-hypertensive drugs is very important. To improve the prognosis of patients with hypertension, we need not only to lower the blood pressure, but also to reduce the artery stiffness. This needs a simple indicator, which can be used to evaluate whether a medicine has improved the artery stiffness or not. This indicator will be useful for physicians to select medicine for the treatment of patients with hypertension.Currently, pulse wave velocity (PWV) and ankle-brachial pressure index (ABI) are employed as indicators not only for arteriosclerosis, but also for the mortality of cardiovascular disease. Owing to the recent development of an easy-to-use, non-invasive device, Form ABI/PWV (Nihon Colin, Aichi, Japan), brachial-ankle PWV (baPWV) is rapidly used as a effective parameter to evaluate the efficacy of anti-hypertensive therapy.Previous clinical studies in anti-hypertension therapy suggested that although different medicines could reduce the blood pressure within normal range, they had different effect in changing the vascular stiffness. baPWV measurement can be used for our valuation of a medicine which is improving the flexibility of artery and guide for proper usage a medicine in anti-hypertension therapy.It has been shown by many clinical studies that angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) are effective for protecting against hypertension-related organ damages. Here, we recorded PP waveforms in the right forearm and rightankle simultaneously using a simple, non-invasive oscillometricmethod and determined baPWV as an index of arterial stiffness to examine the effects of various antihypertensive agents in hypertensive patients. Our conclusion is that SBP, DBP and PP were significantly decreased in all three groups. HR remained unchanged in all three groups (P>0.05) . BaPWV was significantly decreased in the ACEI, CCB, ARB groups. The reductions in baPWV was significantly greater in the ARB group than in the ACEI and CCB groups (one months p<0.01; three months p<0.05). The efficacy of improving artery flexibility is as follows, telmisartan > amlodipine> perindopril. Our results show that telmisartan plays a role in the improvement of artery function of the flexibility outside of anti-hypertensive therapy. The changes of baPWV were significantly greater in three months than in one month in all three grops (p<0.05).Conclusions1. Our study shows that all three medicines, telmisartan, amlodipine and perindopril have the effect of improving the flexibility of artery in anti-hypertensive therapy for one and three months.2. We concluded that telmisartan had better effect than amlodipine and perindopril with regard to improving the flexibility of artery in one and three months of anti-hypertension therapy.3. Our results also suggested that continuous anti-hypertensive treatment with telmisartan , amlodipine and perindopril will have a persistent improvement of the artery flexibility.更多还原