Angiotensin converting enzyme inhibitor cough: Lessons from heart–lung transplantation

Coughing is a frequent side-effect of angiotensin converting enzyme (ACE) inhibitors. Its pathogenesis is thought to be related to the local accumulation of tachykinins although the role of extrinsic cholinergic pathways is unclear. The development of an ACE inhibitor induced cough in two patients who have undergone heart–lung transplantation and in whom cholinergic pathways remain denervated supports the hypothesis of a 'local' mechanism.     

血管紧张素转化酶基因多态性与内皮功能的研究

目的 :探讨血管紧张素转化酶 （ACE）基因多态性与冠心病血管内皮功能的关系。方法 :采用多聚酶链反应（PCR）技术对 2 4例心肌梗死、5 6例心绞痛患者、6 5例正常人的 ACE基因型及血浆内皮素 （ET）、内皮源性舒张因子 （EDRF）进行了检测 ,以 ET/ NO作为内皮功能指标。结果 :心肌梗死组 D等位基因频率显著高于正常对照组 ,DD型患者中的 ET/ NO比值较 型明显升高 （P<0 .0 5 ）。结论 :DD型心肌梗死患者内皮功能受损较重。     

Angiotensin converting enzyme (ACE) gene polymorphism in sarcoidosis in relation to associated autoimmune diseases

Abstract. Papadopoulos KI, Melander O, Orho‐Melander M, Groop LC, Carlsson M, Hallengren B (University of Lund, Malmö University Hospital, Malmö, Sweden). Angiotensin converting enzyme (ACE) gene polymorphism in sarcoidosis in relation to associated autoimmune diseases. J Intern Med 2000; 247: 71–77. Objectives. To investigate the significance of ACE gene insertion/deletion (I/D) polymorphism in the frequency of autoimmune manifestations in sarcoidosis. Design. In patients with sarcoidosis the ACE gene I/D polymorphism was detected with PCR on genomic DNA. The patients with sarcoidosis were divided according to the presence (n = 30) or absence (n = 32) of autoimmune manifestations. The former group was subdivided into thyroid autoimmunity (n = 10), gluten immune reactivity (n = 10) and gastric autoimmunity (n = 17). Settings. The patients were recruited at the Department of Pulmonary Medicine, and the study was conducted at the Department of Endocrinology, University of Lund, Malmö University Hospital, Malmö, Sweden. Subjects. Sixty‐two patients with documented sarcoidosis (30 females, 32 males, median age/range at diagnosis of sarcoidosis 31.5/19–75 years, median age/range at study 47.5/22–81 years) were examined. A total of 107 healthy unrelated subjects without sarcoidosis (60 females, 47 males, median age/range at study 58/40–82 years) served as controls. Results. S‐ACE values were significantly increased in patients compared to controls (P = 0.00001). The same was true in the subgroup of sarcoidosis patients with associated autoimmunity compared with those with isolated sarcoidosis (P = 0.0328). A significant association was seen between ACE gene polymorphism (II, ID, DD genotypes) and S‐ACE levels in both patients and controls according to the order II < ID < DD. The observed genotype frequency distributions in the different study groups agreed the Hardy–Weinberg equilibrium without significant differences between the patients and the controls. Within the group with autoimmune manifestations the DD genotype was significantly over‐represented in X‐ray stage III compared to the other X‐ray stages (P = 0.0181) and a significant increase in the DD genotype in X‐ray stage III (P = 0.035) in the group with autoimmune manifestations compared to isolated sarcoidosis was detected. Conclusion. We confirmed that the S‐ACE levels corresponded to the order II < ID < DD in patients with sarcoidosis as well as in healthy controls. S‐ACE levels were significantly higher in sarcoidosis patients with autoimmune manifestations. The frequency of the DD genotype was significantly increased in patients with autoimmune manifestations and major granuloma mass (X‐ray stage III). The ACE D allele in its homozygous form may confer susceptibility for autoimmune manifestations in sarcoidosis, possibly via the high levels of S‐ACE it encodes.     

Angiotensin converting enzyme inhibitors and risk of lung cancer: A systematic review and meta-analysis

Background:We performed a meta-analysis to determine whether a consistent relationship exists between the use of angiotensin converting enzyme inhibitors (ACEIs) and the risk of lung cancer. Accordingly, we summarized and reviewed previously published quantitative studies.Methods:Eligible studies with reference lists published before June 1st, 2019 were obtained from searching several databases. Random effects’ models were used to summarize the overall estimate of the multivariate adjusted odds ratios (ORs) with 95% confidence intervals (CIs)Results:Thirteen observational studies involving 458,686 ACEI users were included in the analysis, Overall, pooled risk ratios indicate that ACEIs use was not a risk factor for lung cancer (RR 0.982, 95% C.I. 0.873 – 1.104; P = .76). There was significant heterogeneity between the studies (Q = 52.54; P < .001; I2 = 86.07). There was no significant association between ACEIs use and lung cancer in studies with over five years of ACEIs exposure (RR 0.95, 95% C.I. 0.75 – 1.20; P = .70); and ≤ 5years of exposure to ACEIs (RR 0.98, 95% C.I. 0.83 – 1.15; P = .77). There were no statistically significant differences in the pooled risk ratio obtained according to the study design (Q = 0.65; P = .723) and the comparator regimen (Q = 3.37; P = .19).Conclusions:The use of ACEIs was not associated with an increased risk of lung cancer. Nevertheless, well-designed observational studies with different ethnic populations are still needed to evaluate the long-term (over 10 years) association between ACEIs use and lung cancer.     

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。     

血管紧张素转换酶及其基因多态性与血管性痴呆和阿尔茨海默病的关系研究

目的探讨血清血管紧张素转换酶(ACE)活性及ACE基因插入/缺失(I/D)多态性与血管性痴呆(VD)和阿尔茨海默病(AD)的关系。方法应用聚合酶链反应(PCR)检测2002年7月至2004年5月南京医科大学附属脑科医院和江苏大学附属第四医院62例VD、39例AD患者以及50名健康对照者ACE基因I/D多态性;对其中56例VD、33例AD患者和46名健康对照者以毛细管电泳法测定血清ACE活性,并进行统计学比较。结果VD组和AD组血清ACE活性与正常对照组相比差异无显著性意义;未发现ACE基因I/D多态性与VD的相关性;AD组I等位基因频率高于对照组,差异有显著性意义(P<0.05)。结论ACE基因I/D多态性与VD无相关性,ACEI等位基因可能是AD发病的危险因素。     

Inhibition of angiotensin converting enzyme cannot prevent increases in angiotensin II production in coronary circulation

OBJECTIVE—To determine whether inhibition of angiotensin converting enzyme (ACE) can prevent angiotensin II production in the coronary circulation induced by percutaneous transluminal coronary angioplasty (PTCA) in patients with myocardial ischaemia.
DESIGN, PATIENTS—41 patients who underwent elective PTCA and six control subjects who received diagnostic coronary angiography were studied. Patients were divided into two groups according to the chronic administration of ACE inhibitors (group A, 15 patients treated with ACE inhibitors; group B, 26 patients without ACE inhibitors). Blood samples were drawn through catheters placed in the aorta and coronary sinus before and 24 hours after PTCA.
RESULTS—Mean levels of ACE activity in the aorta were significantly lower in patients in group A than in group B. However, mean angiotensin II concentrations in the aorta were not significantly different between the two groups. Differences in basal angiotensin II concentrations between the coronary sinus and aorta, which reflected basal angiotensin II production in the coronary circulation, were not significant among group A, group B, and control subjects. The production of angiotensin II in the coronary circulation was significantly increased 24 hours after PTCA in both group A and group B to the same extent. No significant changes were observed in control subjects 24 hours after diagnostic coronary angiography.
CONCLUSIONS—This study revealed that inhibition of ACE activity by ACE inhibitors could not prevent increases in angiotensin II production in the coronary circulation induced by PTCA.


Keywords: angiotensin converting enzyme; chymase; angioplasty     

血管紧张素I转换酶基因I／D多态性与特发性肺纤维化的相关性研究

目的探讨血管紧张素I转换酶（ACE）基因I／D多态性在特发性肺纤维化（IPF）发病中的作用。方法应用PCR技术检测42例IPF患者（IFP组）和90例健康查体者（对照组）ACE基因I／D多态性,并分析不同基因型和等位基因者IPF发病危险性。结果IPF组DD基因型和D等位基因频率均显著高于对照组（P〈0．05）;与Ⅱ基因型比较,携带DD型和D等位基因个体发生IPF的风险分别增加2．97倍（95％CI为1．13—7．73）和1．96倍（95％CI为1．16—3．32）,P均〈0．05。结论ACE基因I／D多态性与IPF发病有关,DD基因型和D等位基因可能增加IPF的患病风险。     

Angiotensin-converting enzyme (ACE) gene polymorphisms and familial occurrence of sarcoidosis

OBJECTIVES: The aim of this study was to test for genetic linkage and association between polymorphisms of the angiotensin-converting enzyme (ACE) gene and familial occurrence of sarcoidosis. DESIGN, SETTING AND SUBJECTS: German families with more than one member suffering from sarcoidosis were contacted and a DNA bank was established. Sixty-two families (140 patients, 77 females and 63 males, and 104 unaffected relatives) were genotyped for the ACE gene insertion/deletion (I/D) polymorphism and for two flanking variable sites (ACE A-5466C and ACE 4656(CT)2/3). As controls, 100 DNAs from unrelated resident Caucasians (50 females, 50 males) were analysed. ACE allele and genotype frequencies were determined, and parametric linkage and affected sib pair analyses and transmission disequilibrium tests were performed. RESULTS: There was a striking over-representation of the ACE I/D genotype DD in patients with sarcoidosis and their families as compared with controls of the study and well founded genotype frequencies from the literature. The same was evident for the accompanying genotypes CC and 2,2 of the flanking polymorphisms. Linkage between the segregation of ACE alleles and the disorder within families was clearly excluded for simple models of inheritance. However, there was a suggestive but not significant (P = 0.06) excess of allele sharing amongst affected siblings. There was no transmission disequilibrium for any ACE allele or haplotype. CONCLUSIONS: ACE is involved in the pathogenesis of sarcoidosis, but the ACE polymorphisms are not an inherited main cause of the disease. They are more likely to modify the development of the disorder, and the ACE I/D genotype DD might be a promoter to clinical manifestation.     

ACE基因多态性与老年人原发性高血压的关系

目的 探讨血管紧张素Ⅰ转换酶（ACE）基因多态性与老年人原发性高血压（EH）的相关性。方法 采用一步PCR3条引物法,对287例老年EH（高血压组）和301例正常老年人（对照组）进行ACE基因I／D多态性分型,并进行基因型及等位基因频率计数,组间采用χ^2检验进行统计学分析。结果 高血压组DD型基因频率及D等位基因频率分别为10．4％和30．5％,对照组分别为9．3％和31．2％,经χ^2检验,2组间无显著差别（P＞0．05）。结论 ACE基因多态性与老年人原发性高血压（EH）无关。一步PCR3条引物法更准确可靠,可减少DD型错判率。     

糖尿病视网膜病变与血管紧张素转换酶基因缺失多态性的系统评价

采用meta分析系统评价中国汉族人血管紧张素转换酶(ACE)基因缺失(DD)多态性与2型糖尿病视网膜病变的关系.共纳入16篇符合条件的文献,共计2型糖尿病视网膜病变组1 014例,对照组1 135例.结果 显示OR为1.69(95%CI1.19～2.40),合并统计值Z=2.91(P=0.004).汉族人群ACE基因该多态性与糖尿病视网膜病变有关联,糖尿病视网膜病变组DD基因型增多.     

Impact of angiotensin I converting enzyme inhibitors and angiotensin II type 1 receptor blockers on survival in patients with advanced non-small-cell lung cancer undergoing first-line platinum-based chemotherapy

Purpose  The renin-angiotensin system plays a crucial role in maintaining vascular homeostasis. Stimulation of angiotensin II type 1 receptors (AT1R) acts proangiogenically by increasing levels of vascular endothelial growth factor (VEGF). Consequently, cell culture experiments and animal studies have shown antiproliferative effects of AT1R blockers (ARB) and angiotensin I converting enzyme inhibitors (ACEI) in several malignancies. Until now, very limited clinical data for this antiangiogenic effect exists for combinations with antineoplastic chemotherapy. Methods  A total of 287 patients with advanced non-small-cell lung cancer undergoing first-line platinum-based chemotherapy were retrospectively analysed regarding long-term medication with ACEI and ARB as well as histological type, stage, performance status, gender, age, dose-intensity of chemotherapy and survival. Results  Patients receiving either ACEI or ARB had a 3.1 months longer median survival than non-recipients (11.7 vs. 8.6 months, HR 0.56, P = 0.03). This survival advantage could not be attributed to other established risk-factors or dose intensity of chemotherapy. Conclusions  Addition of ACEI or ARB to platinum-based first-line chemotherapy may contribute to prolonged survival in patients with advanced lung cancer.     

血管紧张素转换酶基因多态性与原发性高血压病心肌纤维化的关系

目的　探讨血管紧张素转换酶 ( ACE)基因多态性与原发性高血压病 ( EH)心肌纤维化的关系。方法　以多聚酶链反应 ( PCR)方法检测 168例 EH患者的 ACE基因型 ;放射免疫法检测血清 型前胶原 ( PC )、透明质酸( HA)和层粘蛋白 ( LN)。结果　高血压病心肌纤维化组 DD基因型和 D等位基因频率分别为 0 .42 9和 0 .60 ,显著高于非纤维化组 0 .18和 0 .42 1( P<0 .0 5 )。DD型与 II型比较心肌质量指数、PC 显著升高 ,差异有显著性 ( P<0 .0 5 )。结论　 ACE基因 DD型可能是高血压病心肌纤维化的重要危险因素     

血管紧张素转换酶基因缺失多态性与冠状动脉病变

目的 :探讨血管紧张素转换酶 ( ACE)基因的插入 /缺失 ( insertion/deletion,I/D)多态性与冠状动脉病变的相关性。方法 :应用聚合酶链反应 ( PCR)扩增技术检测 86例行冠状动脉造影患者的 ACE基因 I/D多态性。结果 :冠状动脉异常组的 DD基因型频率 0 .41,D等位基因频率 0 .5 2 ,显著高于冠状动脉正常组的 0 .15和 0 .2 9( P <0 .0 5 ) ;DD基因型与冠状动脉病变有关 ( OR=3.97,P<0 .0 5 )。多支病变与 DD基因型的关系更为密切 ( OR=4.72 ,P<0 .0 5 )。冠状动脉正常组、单支病变组和多支病变组的 DD型频率依次为 0 .15、0 .33和 0 .46( P <0 .0 5 ) ,D等位基因频率为 0 .2 9、0 .44和 0 .5 6( P <0 .0 1)。结论 :ACE基因的 I/D多态性与冠状动脉病变及其严重程度相关 ,DD型及 D等位基因频率随冠状动脉病变及其程度的加重而逐渐升高。在冠状动脉病变患者中 DD及 ID型患者的吸烟率、甘油三酯及血压显著低于 型者 ( P <0 .0 5 ) ,说明 D等位基因及 DD基因型可能是冠心病低危人群冠状动脉病变的重要危险因素之一。     

Left ventricular hypertrophy in relation to systolic blood pressure and the angiotensin converting enzyme I/D polymorphism in Chinese

Objective There is little population-based data on the prevalence and the environmental or genetic determinants of left ventricular hypertrophy （LVH） in China. The purpose of this paper is to study LVH in relation to systolic blood pressure and the angiotensin converting enzyme （ACE） insertion/deletion（I/D） polymorphism in Chinese. Methods We recorded 12- lead ECG （CardioSoft, v4.2） in 1365 residents in the Jingning County, Zhejiang Province, China. LVH was defined according to the gender-specific Sokolow-Lyon and Cornell product ECG criteria. Results Regardless of whether the Sokolow-Lyon or Cornell product ECG criteria was used, the prevalence of LVH （20.7% and 4.8%, respectively） significantly （P〈0.0001） increased with male gender （odds ratio [OR] 2.33 and 7.15） and systolic blood pressure （per 10 mm Hg increase, OR 1.46 and 1.33）. If the Sokolow-Lyon criteria was used, the prevalence of LVH was also influenced by alcohol intake （OR 1.44, P=-0.03） and body mass index （OR 0.83, P=0.0005）. The association between the Sokolow-Lyon voltage amplitude and the ACE I/D polymorphism was dependent on antihypertensive therapy （P=0.01）. In 1262 untreated subjects, but not 103 patients on antihypertensive medication, the ACE DD compared with II subjects had significantly higher Sokolow-Lyon voltage amplitudes （29.8：-0.6 vs. 28.0-3：0.5 mV, P=-0.02） and higher risk of LVH （OR 1.74, 95% CI： 1.12-2.69, P=-0.01）. Conclusion LVH is prevalent in Chinese, and is associated with systolic blood pressure and the ACE D allele. The genetic association might be modulated by antihypertensive therapy（J Geriatr Cardio12009; 6：131-136）.     

血管紧张素转化酶基因的插入／缺失多态性与心肌梗塞关系的研究

本研究运用ＰＣＲ技术对我国人１１６例心肌梗塞（ＭＩ）和１０３例健康作对照的血管紧张素转化酶（ＡＣＥ）基因插入／缺失多态性进行了检测，并与血清ＡＣＥ水平、ＭＩ发病、冠状动脉病变支数等指标进行比较。结果显示ＭＩ组缺失等位基因Ｄ频率０．４６和ＤＤ基因型频率０．２７显著高于对照组的０．３３和０．１２（分别为Ｐ＜０．０１，Ｐ＜０．０５）。同时发现缺失多态性与血清ＡＣＥ水平、ＭＩ组冠状动脉病变支数呈相关性。表明ＡＣＥ基因缺失多态性可能是我国人群ＭＩ发病的重要危险因素之一。