血管紧张素转换酶抑制剂与脑卒中防治

血管紧张素转换酶抑制剂(ACEI)是重要的抗高血压药物之一,很多证据表明,ACEI除具有降血压作用外,对心脑血管还具有重要的保护作用,可以预防中风发生.本文通过检索MEDLINE数据库和Cochrane图书馆光盘数据库的随机对照试验和系统评价,评价ACEI类药物预防脑卒中的机制和在脑卒中防治中的作用,为临床实践提供循证医学的最佳证据.     

依那普利联合厄贝沙坦治疗糖尿病肾病疗效观察

糖尿病肾病(DN)是糖尿病的主要微血管并发症,也是终末期肾病最常见的病因,在我国终末期肾病患者中DN超过15%[1].无论是1型还是2型糖尿病,都有大约40%的患者会出现肾脏损害,而糖尿病患者一旦发生肾脏损害,从微量蛋白尿进入持续性蛋白尿则病情常不可逆转.因此,DN应尽量做到早诊断,早防治.由于基层医院所面临的患者保健意识较差,大多数患者到医院就诊时已经处于持续蛋白尿期,此时严格控制血糖、血压,改善血液流变学,对控制蛋白尿,保护肾功能意义重大.目前临床多单用血管紧张素转换酶抑制剂(ACEI)或血管紧张素受体拮抗剂(ARB)控制血压和蛋白尿,但2者联用较少报道.作者对联用依拉普利和厄贝沙坦治疗DN与单用两者进行对比观察,了解联合用药的效果.     

高血压系列问答(7)如何正确评价和合理使用血管紧张素受体拮抗剂?

不同于美国高血压预防和治疗指南(JNC) - 6 ,美国的JNC - 7首次把血管紧张素受体拮抗剂(ARB)与β受体阻断剂、钙拮抗剂和血管紧张素转换酶抑制剂(ACEI)并列为抗高血压的常用药物推荐。1　ARB有哪些优势?除了具有上一讲中列举的ACEI的类似优势而外,ARB很少引起干咳,不良反应很少,耐受性非常好,不良反应几乎与安慰剂等同。因此,近年来ARB用于高血压治疗的临床应用增长极快。鉴于这类药物在肾脏保护、减少微量白蛋白尿和蛋白尿方面的临床试验证据,对有微量蛋白尿或蛋白尿的患者,尤其II型糖尿病患者,无论有无高血压,均有使用ARB的…     

老年病房循证实践前后心血管疾病合理用药比较

目的了解本科室老年心血管病患者药物治疗的合理性和循证实践效果.方法调查四川大学华西医院老年科1998～1999年及2002～2003年心血管疾病患者(各211例)用药情况,比较循证实践前后临床用药的变化.结果循证实践后,降压药物使用中血管紧张素转换酶抑制剂、利尿剂的地位提高,短效钙拮抗剂、血管紧张素转换酶抑制剂仍然是最常用的种类;联合用药更普遍.治疗冠心病药物中,降脂药物及血管紧张素转换酶抑制剂应用更常见;更注重生活质量,联用抗焦虑治疗.心衰治疗中,β-受体阻滞剂、安体舒通及血管紧张素转换酶抑制剂的应用更受重视.结论循证实践前用药主要根据临床经验及教科书,循证实践后临床用药更注重证据支持,血压控制达标率更理想.合理用药比例由循证实践之前的42%上升为循证实践后的78%.     

开搏通治疗高血压引起干咳30例临床观察

开搏通(卡托普利)是一种血管紧张素转换酶抑制剂，主要作用于肾素-血管紧张素-醛固酮系统(RAAS)，抑制RAAS。系统的血管紧张素转换酶(ACE)阻止血管紧张素I转换成血管紧张素Ⅱ，并能抑制醛固酮的分泌，减少水钠储留，从而降低血压。我们随机选择30例高血压病患者应用卡托普利治疗，观察药物疗效和副作用。     

联合应用血管紧张素转换酶抑制剂和血管紧张素Ⅱ受体拮抗剂对糖尿病肾病患者肾保护作用的临床研究

最新的研究表明,血管紧张素转换酶抑制剂(ACEI)和血管紧张素Ⅱ受体拮抗剂(ARB)均有肯定的肾脏保护作用,并且两药联合应用可相互补充,降低尿蛋白作用优于单用任何一种药物。糖尿病肾病是糖尿病最常见的慢性微血管并发症之一,也是糖尿病患者终末期的主要死因之一。在我国96%以上的糖尿病患者为2型糖尿病,发病后约经10～20年发展为糖尿病肾病,一旦发生糖尿病肾病,其进展至终末期肾功能衰竭的速度比一般肾脏疾病快14倍之多。因此预防和延缓糖尿病肾病发展可提高糖尿病患者的生活质量和生存率,减轻乃至消除蛋白尿是临床治疗的重点所在[1]。1资…     

血压和肾素-血管紧张素系统对糖尿病视网膜病变的影响

目的:糖尿病视网膜病变是1型和2型糖尿病患者常见的微血管并发症之一,可影响视力甚至造成失明,是糖尿病患者康复方面的重要问题。本文综述探讨肾素-血管紧张素系统和血压控制对治疗糖尿病视网膜病变的疗效和机制。资料来源:应用计算机检索Medline1990-01/2004-08的文章,检索词“diabetesmellitus,renin-angiotensinsystem,retinopathy”,并限定语言种类为英文。同时计算机检索万方数据资源系统与中国期刊全文数据库1995-01/2004-08的文章,限定文章语言种类为中文,检索词“糖尿病,视网膜病变,肾素-血管紧张素系统”。资料选择:对资料进行初审,选取研究中包括实验组和对照组的文献,筛除明显不随机的研究,对入选文献查找全文,进一步判断为随机对照研究。纳入标准为①随机对照研究,采用单盲,双盲或非盲法。②研究包含对照组。排除标准:排除重复性非随机对照临床研究。资料提炼:共筛选36篇关于糖尿病视网膜病变与肾素-血管紧张素系统及血压控制临床研究的文章,22个实验纳入标准,排除的14篇为重复性研究。资料综合:22个研究包括探讨高血压及肾素-血管紧张素系统与糖尿病视网膜病变发病之间的关系以及对治疗方法给予评价。发现糖尿病视网膜病变的发生除与代谢控制有关,还受到血压和肾素-血管紧张素系统的影响。严格降压,尤其是血管紧张素转化酶抑制剂和血管紧张素受体拮抗剂的应用可以减少糖尿病视网膜病变的发生和预防失明。结论:许多大型研究显示血压和肾素-血管紧张素系统系统对糖尿病视网膜病变有明确影响,但作用的具体机制仍不明了,需要更多的研究探索。     

苯那普利对以胰岛素治疗2型糖尿病患者的影响

苯那普利是血管紧张素转换酶抑制剂,近年来很多研究证实苯那普利能降低有高血糖及高胰岛素血症患者胰岛素抵抗的药物,已应用于2型糖尿病患者,改善胰岛素敏感性,增敏作用通过扩张血管增加骨骼肌的血流量从而提高骨骼肌对葡萄糖的摄取利用.     

氯沙坦治疗2型糖尿病肾病疗效观察

蛋白尿或白蛋白尿是诊断糖尿病肾病(DN)的重要指标,也是判断DN预后的重要指标[1].降低蛋白尿的治疗措施很多,采用血管紧张素转化酶抑制剂(ACEI)或血管紧张素Ⅱ受体拮抗剂(AT1阻滞剂)阻断肾素一血管紧张素系统(RAS)是常用的选择[2].     

伊贝沙坦对糖尿病肾病的临床疗效

糖尿病(DM)病程超过10年以上者约50％并发糖尿病肾病(DN)，主要表现为高血压、蛋白尿和水肿，继之肾功能不全(CRI)。我们用血管紧张素Ⅱ受体拮抗剂(angiotensin Ⅱ receptor blocker，ARB)类药物伊贝沙坦(安搏维)与血管紧张素转换酶抑制剂(angiotensin coverting enzyme inhibitor，ACEI)类药物苯那普利(洛汀新)治疗糖尿病肾病患者38例，采用随机对照的研究方法，观察伊贝沙坦对DN的疗效以及与苯那普利的临床疗效比较。     

Effect of intensive glycemic control on microalbuminuria in type 2 diabetes. Veterans Affairs Cooperative Study on Glycemic Control and Complications in Type 2 Diabetes Feasibility Trial Investigators

OBJECTIVE: Microalbuminuria can reflect the progress of microvascular complications and may be predictive of macrovascular disease in type 2 diabetes. The effect of intensive glycemic control on microalbuminuria in patients in the U.S. who have had type 2 diabetes for several years has not previously been evaluated. RESEARCH DESIGN AND METHODS: We randomly assigned 153 male patients to either intensive treatment (INT) (goal HbA(1c) 7.1%) or to standard treatment (ST) (goal HbA(1c) 9.1%; P = 0.001), and data were obtained during a 2-year period. Mean duration of known diabetes was 8 years, mean age of the patients was 60 years, and patients were well matched at baseline. We obtained 3-h urine samples for each patient at baseline and annually and defined microalbuminuria as an albumin:creatinine ratio of 0.03-0.30. All patients were treated with insulin and received instructions regarding diet and exercise. Hypertension and dyslipidemia were treated with similar goals in each group. RESULTS: A total of 38% of patients had microalbuminuria at entry and were evenly assigned to both treatment groups. INT retarded the progression of microalbuminuria during the 2-year period: the changes in albumin:creatinine ratio from baseline to 2 years of INT versus ST were 0.045 vs. 0.141, respectively (P = 0.046). Retardation of progressive urinary albumin excretion was most pronounced in those patients who entered the study with microalbuminuria and were randomized to INT. Patients entering with microalbuminuria had a deterioration in creatinine clearance at 2 years regardless of the intensity of glycemic control. In the group entering without microalbuminuria, the subgroup receiving ST had a lower percentage of patients with a macrovascular event (17%) than the subgroup receiving INT (36%) (P = 0.03). Use of ACE inhibitors or calcium-channel blockers was similarly distributed among the groups. CONCLUSIONS: Intensive glycemic control retards microalbuminuria in patients who have had type 2 diabetes for several years but may not lessen the progressive deterioration of glomerular function. Increases in macrovascular event rates in the subgroup entering without albuminuria who received INT remain unexplained but could reflect early worsening, as observed with microvascular disease in the Diabetes Control and Complications Trial.     

Should all Pima Indians with type 2 diabetes mellitus be prescribed routine angiotensin-converting enzyme inhibition therapy to prevent renal failure?

OBJECTIVE: To determine how effective angiotensin-converting enzyme (ACE) inhibitors must be in preventing diabetic nephropathy to warrant early and routine therapy in all Pima Indians with type 2 diabetes mellitus. DESIGN: A computerized medical decision analysis model was used to compare strategy 1, screening for microalbuminuria and treatment of incipient nephropathy as currently recommended with ACE inhibitor therapy, with strategy 2, a protocol wherein all patients were routinely administered an ACE inhibitor 1 year after diagnosis of type 2 diabetes mellitus. The model assumed that ACE inhibitors can block, at least in part, the pathogenic mechanisms responsible for early diabetic nephropathy (microalbuminuria). RESULTS: The model predicted that strategy 2 would produce more life-years at less cost than strategy 1, if routine drug therapy reduced the rate of development of microalbuminuria by 21% in all patients. Only a 9% reduction in the rate of development of microalbuminuria was cost-effective at $15,000 per additional life-year gained, and only a 2.4% reduction was cost-effective at $75,000 per additional life-year gained for strategy 2 over strategy 1. CONCLUSIONS: Routine ACE inhibitor therapy in Pima Indians with type 2 diabetes mellitus could prove more effective and even cost saving than the currently recommended approach of microalbuminuria screening. A prospective trial examining this goal should be considered.     

2型糖尿病患者血清LDL亚组份与微量白蛋白尿的相关性

目的：探讨2型糖尿病患者LDL亚组份改变与糖尿病肾病及其血管病变的关系。方法：用非变性梯度凝胶电泳法,测定54例2型糖尿病患者血清LDL亚组份与UANR,比较不同UAER的2型糖尿病患者的LDL亚组份变化。结果：伴微量白蛋白尿2型糖尿病患者血清LDL亚组份以小颗粒LDL者较多（19/24比6/30,P＜0.0001）,小颗粒LDL和UAER及ACR有显著相关性。讨论：2型糖尿病肾病患者血清中主要含有小颗粒的LDL,是2型糖尿病肾病患者心血管病变的发生率和死亡率增高的重要原因之一。     

Lack of management of cardiovascular risk factors in type 2 diabetic patients

Effective management of diabetic patients includes comprehensive control for not only blood sugar, but also other cardiovascular risk factors. We assessed whether haemoglobin A1c (A1C) concentrations, blood pressure, low density lipoprotein (LDL) cholesterol levels and microalbuminuria were regularly measured in 281 patients with type 2 diabetes who received care for over 1 year in the Department of Family Medicine located in an urban area of Korea. Subsequently, in patients with A1C > 7%; blood pressure >130/80 mmHg; LDL cholesterol levels >100 mg/dl; or microalbuminuria, we evaluated the status of management for those cardiovascular risk factors. Physicians were most likely to measure A1C levels (98.6%), but less likely to measure microalbuminuria (56.2%), LDL cholesterol (73.7%), or blood pressure (74.4%). Patients whose A1C levels were above the goal (78.2%) were likely to receive optimal therapy. In contrast, only 21.1% of patients with uncontrolled blood pressure and 5.3% of patients with LDL cholesterol levels above the target range received optimal management. Of the 36 patients with microalbuminuria or overt proteinuria, 66.7% took angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. Measurement of parameters indicating cardiovascular risk factors in type 2 diabetic patients was not optimal, particularly regular measurements for microalbuminuria and for controlling LDL-cholesterol and blood pressure. These findings indicate a need for greater education of comprehensive cardiovascular management in type 2 diabetic patients and their physicians.     

Cost-effectiveness of early irbesartan treatment versus control (standard antihypertensive medications excluding ACE inhibitors, other angiotensin-2 receptor antagonists, and dihydropyridine calcium channel blockers) or late irbesartan treatment in patients with type 2 diabetes, hypertension, and renal disease

OBJECTIVE: The aim of this study was to determine the most cost-effective time point for initiation of irbesartan treatment in hypertensive patients with type 2 diabetes and renal disease. RESEARCH DESIGN AND METHODS: This study was a Markov model-simulated progression from microalbuminuria to overt nephropathy, doubling of serum creatinine, end-stage renal disease, and death in hypertensive patients with type 2 diabetes. Two irbesartan strategies were created: early irbesartan 300 mg daily (initiated with microalbuminuria) and late irbesartan (initiated with overt nephropathy). These strategies were compared with control, which consisted of antihypertensive therapy with standard medications (excluding ACE inhibitors, other angiotensin-2 receptor antagonists, and dihydropyridine calcium channel blockers) with comparable blood pressure control, initiated at microalbuminuria. Transition probabilities were taken from the Irbesartan in Reduction of Microalbuminuria-2 study, Irbesartan in Diabetic Nephropathy Trial, and other published sources. Costs and life expectancy, discounted at 3% yearly, were projected over 25 years for 1,000 simulated patients using a third-party payer perspective in a U.S. setting. RESULTS: Compared with control, early and late irbesartan treatment in 1,000 patients were projected to save (mean +/- SD) 11.9 +/- 3.3 million dollars and 3.3 +/- 2.7 million dollars, respectively. Early use of irbesartan added 1,550 +/- 270 undiscounted life-years (discounted 960 +/- 180), whereas late irbesartan added 71 +/- 40 life-years (discounted 48 +/- 27) in 1,000 patients. Early irbesartan treatment was superior under a wide-range of plausible assumptions. CONCLUSIONS: Early irbesartan treatment was projected to improve life expectancy and reduce costs in hypertensive patients with type 2 diabetes and microalbuminuria. Later use of irbesartan in overt nephropathy is also superior to standard care, but irbesartan should be started earlier and continued long term.     

Angiotensin-converting enzyme gene polymorphism as a potent risk factor for developing microalbuminuria in Japanese patients with type 2 diabetes mellitus: a 9-year follow-up study

To clarify the risk factors for developing microalbuminuria in patients with type 2 diabetes mellitus, a longitudinal observational study was performed. Fifty patients with normoalbuminuria were recruited and treated conventionally for 9 years. Polymorphisms of the angiotensin-converting enzyme (ACE) gene and the angiotensinogen M235T polymorphism were examined. During the study period, 12 of the 50 patients developed microalbuminuria; no patients progressed to macroalbuminuria. Multiple logistic regression analysis was performed using age, duration of diabetes, body mass index, haemoglobin A1c' blood pressure, serum lipid profile and genetic polymorphisms as independent variables and development of microalbuminuria as the dependent variable. The D allele of the ACE gene was an independent and significant variable. We conclude that the ACE gene D allele polymorphism is a potent risk factor for developing microalbuminuria in type 2 diabetic patients.     

Prevalence of diabetes complications in adolescents with type 2 compared with type 1 diabetes

OBJECTIVE: To compare the prevalence of diabetes complications and their risk factors in youth with type 1 versus type 2 diabetes. RESEARCH DESIGN AND METHODS: We performed a comparative clinic-based study of 1,433 patients with type 1 diabetes and 68 patients with type 2 diabetes aged <18 years from New South Wales, Australia. Retinopathy was assessed by seven-field stereoscopic retinal photography; albumin excretion rate from three consecutive, timed, overnight urine collections; peripheral neuropathy by thermal and vibration threshold; and autonomic neuropathy by pupillometry. HbA(1c) (A1C) and lipids were measured in all patients and C-peptide in patients with type 2 diabetes. RESULTS: In patients with type 1 versus type 2 diabetes, median (interquartile range) age was 15.7 years (13.9-17.0) and 15.3 years (13.6-16.4), respectively (P = 0.2), whereas median diabetes duration was 6.8 years (4.7-9.6) and 1.3 years (0.6-3.1), respectively (P < 0.0001). Retinopathy was significantly more common in patients with type 1 diabetes (20 vs. 4%, P = 0.04), while microalbuminuria and hypertension were significantly less common (6 and 16% in type 1 diabetes vs. 28 and 36% in type 2 diabetes). Rates of peripheral and autonomic neuropathy were similar (27 and 61% in type 1 diabetes vs. 21 and 57% in type 2 diabetes). In multivariate analyses, microalbuminuria was significantly associated with older age (odds ratio 1.3 [95% CI 1.2-1.5], P < 0.001) and systolic hypertension (3.63 [2.0-6.3], P < 0.001) in type 1 diabetes, while only higher A1C (1.7 [1.3-2.9], P = 0.002) was significant in patients with type 2 diabetes. CONCLUSIONS: Youth with type 2 diabetes have significantly higher rates of microalbuminuria and hypertension than their peers with type 1 diabetes, despite shorter diabetes duration and lower A1C. The results of this study support recommendations for early complications screening and aggressive targeting of glycemic control in patients with type 2 diabetes.     

2型糖尿病患者血清C反应蛋白与微量蛋白尿的关系

目的 探讨2型糖尿病患者C反应蛋白(CRP)的变化及微量白蛋白尿(MAU)与CRP的关系。方法 对80例2型糖尿病患者根据尿白蛋白排泄率(UAER)分为正常蛋白尿组、微量蛋白尿组 ,分别进行空腹血糖和CRP测定。并与50例正常对照组比较。结果 2型糖尿病患者CRP明显高于正常对照组(p<0.01) ,而微量蛋白尿组CRP值明显高于正常蛋白尿组(p<0.05)。结论 CRP与糖尿病及其血管并发症有关。微量蛋白尿是心血管病的预测指标 ,慢性炎症可能起媒介作用     

Large scale clinical trials in prevention of end-stage renal disease due to type 2 diabetes with angiotensin receptor antagonists

Abundant data from studies of patients with proteinuric nephropathy confirm that angiotensin-converting-enzyme(ACE) inhibitors slow the progression of kidney disease more effectively than many other medications. Three studies, RENAAL, IDNT, and IRM2 provide additional evidence with regard to this issues. In IDNT, two doses of irbesartan were administered to patients with type 2 diabetes and hypertension who had normal glomerular filtration rate. The diminution of proteinuria indicates protection from ongoing kidney damage that would probably translate into the preservation of the glomerular filtration rate in the longer term. In RENAAL and IRM2 patients who had higher grade proteinuria and established renal insufficiency were enrolled. In patients whose disease was at this more advanced phase, losartan or irbesartan led to lower levels of proteinuria, lower rates of decline in the glomerular filtration rate, and later onset of end-stage renal disease than the control medications, amlodipine and a mixture of drugs. Moreover, these beneficial effects are independent of the reduction in blood pressure.     

Cardiovascular autonomic neuropathy is associated with microalbuminuria in older patients with type 2 diabetes

OBJECTIVE: Cardiovascular autonomic neuropathy is associated with microalbuminuria in young and middle-aged patients with type 2 diabetes. We examined this relationship and the potential mediating role of blood pressure in older patients. RESEARCH DESIGN AND METHODS: At least two of three components of cardiovascular autonomic testing were completed by 132 patients (mean age 70 +/- 5.6 years). Relative rankings on each of the components were averaged to create a summary heart rate variability (HRV) measure. The urine microalbumin-to-creatinine ratio (milligrams albumin/grams creatinine) was calculated. Blood pressure was measured at rest and by 24-h ambulatory recording. RESULTS: Urine microalbumin-to-creatinine ratio was higher in those with lower HRV (mean urine microalbumin-to-creatinine ratio 28, 56, and 191 mg/g from the highest to lowest tertile of HRV; P < 0.0001). Resting and ambulatory blood pressure levels were negatively correlated with HRV and positively correlated with urine microalbumin-to-creatinine ratio. In multivariate analysis adjusting for age, duration of diabetes, HbA(1c), and HDL cholesterol, HRV and blood pressure were both independently associated with urine microalbumin-to-creatinine ratio, with no evidence that either mediates the effect of the other. CONCLUSIONS: Cardiovascular autonomic neuropathy and blood pressure are independently associated with microalbuminuria in older patients with type 2 diabetes.