早期使用β受体阻断剂治疗轻中度心功能不全

目的比较早期或后期给予β受体阻断剂(BB)治疗轻中度心功能不全的安全性和有效性。方法入选94例患者,随机分为两组,分别早期或后期给予BB治疗。比较两组间用药耐受率、纠正心功能不全时间和无严重心血管事件生存时间的差别。结果87例病例耐受,两组的耐受率没有统计学差别。但早期使用BB较后期使用心功能不全纠正需要的时间短,严重心血管事件发生率低,无心血管事件生存时间更长,有统计学差别。结论对轻中度心功能不全患者,早期使用BB安全,能更快的纠正心功能不全,获益更大。     

血管紧张素转化酶抑制剂的临床应用

大量研究已经表明：ＡＣＥＩ类药物治疗高血压病和充血性心力衰竭病人安全有效；在急性心肌梗死早期应用ＡＣＥＩ治疗对心脏具保护作用；部分ＡＣＥＩ药物有增强机体对胰岛素的敏感性、降低胰岛素抵抗的作用。推测未来ＡＣＥＩ的应用将扩大。     

依那普利不对DOCA-盐诱导的高血压大鼠发生影响

目的　观察依那普利对DOCA -盐诱导的高血压大鼠 (DHR)血压、主动脉结构、血浆内皮素 (ET 1)和主动脉组织ET 1mRNA表达的影响 ,并探讨依那普利不影响其变化的可能机制。方法　 3 0只SD大鼠 ,等分和制作为正常对照组、模型对照组、依那普利组。依那普利组给予依那普利 2 0mg·kg- 1 ·d- 1 灌胃。每周测血压一次。四周后处死 ,抽动脉血放免法测血浆ET -1浓度、肾素活性 (PRA) ,取主动脉分别作病理分析和RT -PCR检测ET 1mRNA表达。结果　模型对照组血压明显上升 ,血管平滑肌细胞 (VSMC)肥大 ,弹力纤维层增厚 ,中层厚度及中层厚度 /内径明显增大。依那普利组血压也明显上升 ,四周后仅比模型对照组低 9mmHg ,两者相比差别无统计学意义 ,主动脉亦明显重塑。血浆肾素活性 :模型对照组和依那普利组显著低于正常对照组 ;依那普利组与模型对照组相比无差别 ;血浆ET 1及ET 1mRNA表达 :模型对照组和依那普利组显著高于正常对照组 ;依那普利组与模型对照组相比无差别。结论　依那普利不能改善DHR主动脉重塑 ,可能是DHR主动脉局部肾素 -血管紧张素系统 (RAS)受到抑制 ,低水平的RAS对血管组织增殖无重要作用     

血管紧张素转化酶抑制剂所致咳嗽与血管紧张素转化酶基因型相关性的研究

目的　探讨老年原发性高血压患者口服血管紧张素转换酶抑制剂 (ACEI )后发生咳嗽的机制。方法　应用聚合酶链反应 (PCR) ,检测老年原发性高血压患者口服ACEI后发生咳嗽与无咳嗽者的血管紧张素转化酶 (ACE)基因多态性 ,检测并比较两组患者血清ACE水平及ACE水平预测高血压患者口服ACEI引起咳嗽的敏感性和特异性。结果　ACEI所致咳嗽组ACE基因Ⅱ型的频率为4 0 % ,显著高于无咳嗽组 (2 0 % ,P <0 0 5 ) ,Ⅰ等位基因频率为 6 0 % ,显著高于无咳嗽组 (4 1% ,P <0 0 1)。两组患者血清ACE水平在DD型、ID型、Ⅱ型依次减低。咳嗽组血清ACE水平显著低于无咳嗽组 (P <0 0 0 1) ,血清ACE水平预测ACEI引起咳嗽的敏感性和特异性分别为 81%和 78%。结论　老年高血压患者口服ACEI所致咳嗽与血清ACE水平及ACE基因多态性有关。     

黄葵胶囊联合 ACEI 及 ARB 治疗早期糖尿病肾病的临床研究

目的：探讨黄葵胶囊联合血管紧张素转换酶抑制剂（ ACEI）及血管紧张素Ⅱ受体拮抗剂（ ARB）治疗早期糖尿病肾病（ DN）的临床效果。方法将60例早期DN患者随机分为两组,各30例。对照组给予依那普利片和厄贝沙坦片治疗,观察组在对照组治疗基础上给予黄葵胶囊。对比两组治疗前后尿白蛋白排泄率（ UAER ）、醛固酮（ ALD ）、血管紧张素II （AII）、糖化血红蛋白（HbA1c）、血肌酐、尿素氮、血糖及平均动脉压（MAP）的变化,并观察药物不良反应发生情况。结果两组治疗前UAER、ALD、AII、HbA1c、血肌酐、尿素氮、血糖及MAP比较,差异均无统计学意义（ P ＞0．05）;两组治疗后血糖均无明显变化（ P ＞0．05）;观察组治疗后UAER、ALD、AII、HbA1c、血肌酐、尿素氮和MAP均低于治疗前（ P ＜0．05）;对照组治疗后UAER、ALD、AII、尿素氮和MAP均低于治疗前（ P ＜0．05）;两组治疗后比较,观察组UAER、ALD、AII、HbA1c、血肌酐和尿素氮均低于对照组（ P ＜0．05或P ＜0．01）。两组患者治疗期间不良反应发生率比较,差异无统计学意义（ P ＞0．05）。结论黄葵胶囊联合ACEI及ARB治疗早期DN效果显著,且使用安全。     

卡托普利对高血压心脏病心力衰竭血液动力学的影响

６７例高心病心力衰竭患者分为卡托普利组（３４例）和硝酸异山梨酯对照组（３３例）．结果用药前和用药后无创血液动力学测定相比较，卡托普利组每搏量指数、心输出量和心脏指数增加，总外周阻力和左室射血阻抗降低；对照组每搏量指数稍增加，总外周阻力和左室射血阻抗增加。两组间比较，上述指标差异均为显著（Ｐ＜０．０１）。     

肾上腺皮质激素与ACEI/ARB治疗局灶节段性肾小球硬化临床疗效比较

目的:比较ACEI/ARB与肾上腺皮质激素对非肾病综合征表现的局灶节段性肾小球硬化(FSGS)患者的临床疗效。方法:回顾性分析34例原发性FSGS患者的临床表现、实验室指标及治疗情况,比较ACEI/ARB组与肾上腺皮质激素组的临床疗效。结果:本研究共纳入34例原发性FSGS患者,男22例,女12例,男女比例1.83∶1,中位发病年龄38(22～80)岁,ACEI/ARB组和激素组治疗后蛋白尿水平较基础值均下降,但两组在治疗3个月,6个月时降蛋白尿作用差异无统计学意义,治疗3个月,6个月,12个月及24个月的临床缓解率差异无统计学意义。结论:ACEI/ARB与单纯激素治疗非肾病综合征FSGS患者的疗效相当,今后有待开展大样本、多中心、前瞻性对照研究,为该类患者制定合理有效治疗方案提供理论依据。     

Relationship Between ABCB1 Polymorphisms,Thromboelastography and Risk of Bleeding Events in Clopidogrel-Treated Patients With ST-Elevation Myocardial Infarction

Introduction

This study sought to investigate the relationship of polymorphisms in ABCB1 and the predictive value of thromboelastography (TEG) on bleeding risk in clopidogrel-treated patients with ST-elevation myocardial infarction (STEMI).

Methods

467 consecutive patients with STEMI undergoing percutaneous coronary intervention (PCI) were enrolled. Twenty tag single nucleotide polymorphisms (SNPs) selected from ABCB1 gene and CYP2C19*2, *3, *17 were detected by the ligase detection reaction. Platelet reactivity was assessed by TEG. The follow-up period was 12 months.

Results

By receiver operating characteristic curve analysis, the TEG platelet mapping assay value of ADP inhibition had the best predictive value of bleeding academic research consortium definition (BARC) ≥ 3b bleedings, yielding an area under the curve (AUC) of 0.707 (95% CI 0.662-0.749, p = 0.009; cut-off value > 93.4%). ADP inhibition can also predict BARC ≥ 3 bleedings with an AUC of 0.594 (95% CI 0.546-0.640, p = 0.05; cut-off value > 92.5%). After adjustment for established risk factors of bleeding including the gain of function CYP2C19*17 allele, age, female gender, renal function, the multivariable logistic regression model demonstrated that ADP inhibition > 92.5% (OR 2.247, 95%CI 1.082-4.665, P = 0.03), carriage of rs1045642 (OR 2.943, 95%CI 1.195-7.247, P = 0.019) and rs7779562 (OR 0.453, 95%CI 0.219-0.936, P = 0.032) were independent predictors of BARC ≥ 3 bleedings. These associations were validated in a second cohort of 504 STEMI patients.

Conclusions

In STEMI patients treated with clopidogrel after PCI, the ABCB1 tag SNP rs1045642 is associated with higher risk of bleedings while rs7779562 is associated with lower bleeding risk, and ADP inhibition in TEG has a predictive value of bleedings.     

雷米普利临床研究证据的综合评价——循证评药实用方法初步探索

目的评估雷米普利对各种适应症的效果和安全性,为医院药品购进和管理、临床医生用药提供研究依据,并探讨基于证据进行药物评估的实用方法.方法采用系统评价和卫生技术评估原则,检索Medline,CochraneLibrarv及药业公司提供有关资料,全面收集全世界范围内发表的有关雷米普利(Ramipril)的研究文章,对纳入研究逐个进行质量评价,并将所有研究结果进行综合分析.结果收集到214篇提到雷米普利的文章,符合纳入标准的共18篇,病例数共计31139例.研究内容包括高血压、糖尿病、心衰、心肌梗塞、肾病、心脑血管病的二级预防.结论根据现有证据,我们认为此药是一种有效、安全、易使用的药物,值得推广应用.     

REMODELLING OF RESISTANCE ARTERIES BY TREATMENT WITH ENALAPRIL IN THE NEW ZEALAND GENETICALLY HYPERTENSIVE RAT

1. New Zealand genetically hypertensive (GH) rats were treated with enalapril from the age of 4 to 10 weeks and the effects of treatment on the structure of mesenteric resistance arteries (MR A) was measured by use of stereological analysis of stained sections and by myograph techniques. 2. Tail-cuff blood pressure (BP) was measured weekly and intra-arterial BP recorded just before MRA were either fixed by perfusion or mounted on a myograph. 3. Stereological techniques (Cavalieri and optical dissector) were used to determine media and lumen volume, fraction of smooth muscle (SM) within the media and SM cell density. For MRA mounted on the myograph, lumen diameter, media thickness, active tension and active pressure were recorded. 4. BP was significantly (P<0.0001) lowered by enalapril throughout the experiment. Intra-arterial BP and left ventricular (LV) mass were also significantly lower in the enalapril treated GH rats (P<0.0001). 5. Stereological measurements showed that enalapril treatment significantly (P<0.0001 reduced media volume by 50%, doubled lumen volume (P<0.0001)), reduced the fraction of SM in the media (P<0.04), and had no effect on the number of SM cell layers or on SM cell density. 6. Myograph measurements showed a decrease in the ratio media thickness/lumen diameter which was accompanied by a decrease in maximum active tension and pressure development. 7. In the GH rat early treatment with enalapril causes a true loss of medial tissue that is not simply due to rearrangement of existing media around an enlarged lumen. 8. The reduction in media without changes in SM cell density or in the number of layers of SM cells supports the suggestion that angiotensin-converting enzyme (ACEI) have an effect on cell matrix.