ACE inhibitors in the elderly

As the population with hypertension becomes older, it is important to determine the properties of angiotensin-converting enzyme (ACE) inhibitors in the elderly. The pharmacokinetics and efficacy of captopril, enalapril, and a new once-daily ACE inhibitor, quinapril for the treatment of hypertension in young and elderly patients are reviewed, and the safety profiles of these agents in young and elderly patients are discussed. Although the safely profile of all three drugs is very favorable, quinapril tended to be better tolerated by patients of all ages in comparative clinical trials.     

N-acetylcysteine potentiates the antihypertensive effect of ACE inhibitors in hypertensive patients

Sulfhydryl group donors, such as N-acetylcysteine (NAC), may enhance the antihypertensive effect of some drugs through a nitric oxide (NO) mechanism. It has been observed that the hypotensive effect of angiotensin-converting enzyme inhibitors (ACEIs) is, at least partially, mediated by NO. We performed a within patient crossover study with the aim to investigate the potential effect of NAC on the ACEI antihypertensive action, via an NO-dependent mechanism. We studied 18 smoker (> 10 years of habit and > 10 cigarettes daily) hypertensive patients (15 males and three females, aged 69 +/- 5 years) on ACEI therapy (11 captopril and seven enalapril). Patients were randomly allocated to two treatment arms. In one arm, the patients (n = 10) initially received the addition of NAC (600 mg t.i.d.) to the ACEI regimen. In the other group (n = 8), the patients remained only on ACEI. After 21 days, the therapeutic patterns were crossed. The first group received only ACEI, and the second group received ACEI and NAC and completed other 21-day treatment period. We evaluate the effect of NAC on each patient by ambulatory blood pressure monitoring (ABPM), performed at the end of each therapeutic regimen. A significant decrease in systolic and diastolic 24-h blood pressure (24 hBP) and daytime BP (dtBP) was achieved with the combination of ACEI and NAC (ACEI + NAC) when compared to the period with only ACEI: 24 hBP = 146.1 +/- 4.2 vs 137 +/- 3.1 (p < 0.05) and 89.2 +/- 2.8 vs 83.5 +/- 3.7mmHg (p = 0.01). DtBP: 149.7 +/- 5.6 vs 141 +/- 3.7 and 92.1 +/- 4 vs 86 +/- 3.2 (both, p < 0.05). No significant difference was observed in night-time BP (ntBP). The NAC effect was not statistically different for the two ACEIs. In conclusion, the addition of NAC to an ACEI potentiates its antihypertensive effect during 24hBP and dtBP in smoker hypertensives. This effect may be mediated by an NO-dependent mechanism, probably through the protective effect of NAC on NO oxidation.     

Effects of celecoxib on ambulatory blood pressure in hypertensive patients on ACE inhibitors

Nonselective nonsteroidal anti-inflammatory agents have been shown to attenuate the antihypertensive efficacy of ACE inhibitors with average increases in systolic blood pressure (BP) of 5 to 10 mm Hg. Less is known about the specific cyclooxygenase-2 (COX-2) inhibitors now widely used for the treatment of arthritis. The objective of this study was to determine the effects of celecoxib compared with placebo on 24-hour BP levels in ACE inhibitor-treated patients with hypertension. This was a randomized, double-blind, placebo-controlled, parallel-group clinical trial involving 178 men and women (mean age, 53 years) with essential hypertension who were treated and controlled with lisinopril monotherapy (10 to 40 mg daily). Baseline BP values were obtained using 24-hour ambulatory recordings. Patients received either celecoxib, 200 mg twice daily (twice the recommended dose for osteoarthritis) (n=91), or placebo (n=87) for 4 weeks, and changes in the 24-hour BP, body weight, and clinical laboratory parameters were assessed. Mean changes from baseline in the 24-hour systolic and diastolic BP were 2.6/1.5+/-0.9/0.6 mm Hg on celecoxib versus 1.0/0.3+/-1/0.6 mm Hg on placebo (P=0.34 for systolic BP; P=0.45 for diastolic BP). The proportion of patients whose 24-hour BP increased by at least 5, 10, 15, or 20 mm Hg were also similar on celecoxib and placebo. No changes in body weight, serum creatinine, or potassium occurred in either group. Thus, these data demonstrate that high doses of celecoxib have no significant effect on the antihypertensive effect of the ACE inhibitor lisinopril. The placebo-subtracted changes observed in 24-hour BP (1.6/1.2 mm Hg) are less than what has been reported for nonselective nonsteroidal anti-inflammatory agents in ACE inhibitor-treated patients.     

老年高血压患者血管紧张素转换酶和醛固酮合酶基因多态性与肾素血管紧张素醛固酮的关系

目的分析老年高血压晨峰患者血管紧张素转换酶(ACE)基因I/D、醛固酮合酶(CYP11B2)基因-344C/T多态性与肾素-血管紧张素-醛固酮系统(RAAS)的相关性。方法选择2016年2月~2017年12月云南省第一人民医院老年病科门诊及住院的老年原发性高血压患者200例,根据清晨血压水平分为晨峰增高组58例和非晨峰增高组142例。分析2组患者ACE基因I/D、CYP11B2基因-344C/T多态性和血浆RAAS参数的差异。结果 2组ACE基因型和等位基因频率比较,差异有统计学意义(χ^2=38.020,P=0.000;χ^2=42.040,P=0.000)。2组CYP11B2基因型和等位基因频率比较,差异无统计学意义(χ^2=0.261,P=0.878;χ^2=0.198,P=0.656)。晨峰增高组DD+TC、DD+TT基因型比例明显高于非晨峰增高组,差异有统计学意义(22.4%vs 3.5%,12.1%vs 2.1%,P<0.01);晨峰增高组II+TT、II+TC基因型比例明显低于非晨峰增高组,差异有统计学意义(13.8%vs 29.6%,P<0.05;5.2%vs 22.5%,P<0.01)。晨峰增高组血浆肾素、血管紧张素Ⅱ和醛固酮水平明显高于非晨峰增高组,差异有统计学意义(P<0.05,P<0.01)。logistic回归分析显示,DD+CC、DD+TC、DD+TT、肾素、血管紧张素Ⅱ为血压晨峰的重要影响因素(OR=8.084,95%CI:1.261~51.832,P=0.027;OR=14.459,95%CI:3.804~54.964,P=0.000;OR=9.753,95%CI:2.255~42.181,P=0.002;OR=1.816,95%CI:1.258~2.620,P=0.001;OR=0.634,95%CI:0.437~0.921,P=0.017)。结论 ACE基因DD型、肾素、血管紧张素Ⅱ是血压晨峰形成的主要影响因素。     

Diagnosis and treatment of hypertensive crises in the elderly patients

Hypertension is a common clinical problem in the elderly worldwide and physicians of all types are likely to encounter patients with hypertensive urgencies and emergencies in these patients. Although various terms have been applied to these conditions, they are all characterized by acute elevations in blood pressure and evidence of end-organ injury. Prompt, but carefully considered therapy is necessary to limit morbidity and mortality. A wide range of pharmacologic alternatives are available to the practitioner to control blood pressure and treat complications in these patients. The management of the elderly patient with hypertensive crises needs to include close monitoring and a gentle decline in blood pressure to avoid catastrophic complications, exacerbation of ischemic myopathy, and vascular insufficiency.     

The role of ACE inhibitors and angiotensin receptor blockers in the treatment of hypertension and cardiovascular disease

Pharmacologic attenuation of the renin-angiotensin-aldosterone system (RAAS) either through angiotensin-converting enzyme (ACE) inhibition or angiotensin II receptor blockade now occupies a central role in the management of hypertension, diabetes, heart failure, and cardiovascular and renal disease. Although our understanding and use of these agents has expanded significantly over the past decade, the relative and differential benefits of ACE inhibitors and angiotensin receptor blockers (ARBs) are still not entirely clear. The data continue to support the first-line use of ACE inhibitors for all indications. Results for combination ACE inhibitor and ARB therapy in clinical outcome trials have been disappointing and do not support its use. New strategies for RAAS modulation bring hope for further progress in the treatment of hypertensive and cardiovascular disease.     

老年高血压病能量消耗的临床研究

目的通过测定老年高血压病人的能量代谢的变化，探讨血压和能量消耗的关系，为进一步研究老年高血压病人的能量代谢规律提供参考。方法从我院健康查体的老年男性患者中，选择２组作为研究对象：高血压组１６例，平均年龄为７０±８岁；健康对照组１７例，平均年龄为６５±７岁。同时对他们进行静息能量消耗（ＲＥＥ）、血压、人体测量指标、皮褶厚度等的测量。结果高血压组的ＲＥＥ和收缩压显著高于对照组（Ｐ＜０．０１）。高血压组收缩压和ＲＥＥ之间呈显著的正相关（（ｒ＝０．５２９８，Ｐ＜０．０１）。高血压组的体密度、皮褶厚度之和与体脂百分含量显著高于对照组（Ｐ＜０．０１）。结论老年高血压患者有着较高的ＲＥＥ水平，其收缩期血压和ＲＥＥ呈显著的正相关。提示改善老年患者的身体构成、胰岛素抵抗等代谢紊乱措施，有利于控制血压稳定与保持适度的ＲＥＥ水平     

Complete spontaneous remission of cough induced by ACE inhibitors during chronic therapy in hypertensive patients.

The files of 172 consecutive hypertensive patients who received captopril or enalapril have been reviewed and the patients questioned on the development of chronic dry cough, persisting for at least two months. Forty patients had cough that was attributed to the drugs. Thirteen of them discontinued the drugs because of this adverse effect. In 15 of the 27 patients (55%) who continued receiving ACE inhibitors (7 males, 8 females, aged 65.4 +/- 9.9 years) the cough had spontaneously disappeared after 3.9 +/- 1.9 months of continued unaltered administration of these drugs and without any treatment aimed against this symptom. All patients were followed for at least four months after disappearance of cough, without recurrences. This finding may discourage withdrawal of ACE inhibitors from many patients who develop cough. Continuation of ACE inhibitors for at least several months, despite cough, (if the cough is not too severe) is probably justifiable.     

2种单片复方制剂治疗老年原发性高血压的疗效对比

目的观察单片复方制剂(SPC)厄贝沙坦150mg/氢氯噻嗪12.5mg与氨氯地平5mg/缬沙坦80mg治疗24周对老年原发性高血压患者的降压疗效及安全性。方法选择已使用单药治疗但血压未达标的老年(60～80岁)高血压患者196例,随机分成两组,A组98例换用厄贝沙坦150mg/氢氯噻嗪12.5mg,B组98例换用氨氯地平5mg/缬沙坦80mg,随访24周,记录血压、心率及不良反应;监测血生化指标;测定左心室质量指数(LVMI);测定颈动脉内膜中层厚度(IMT),计算斑块积分;进行尿蛋白检测。结果 181例完成了24周随访研究;两组收缩压、舒张压和脉压在用药后第4周开始明显下降[与入组时同组相比,A组收缩压(147.5±9.3)比(159.5±5.6)mmHg、舒张压(83.5±7.7)比(90.6±7.9)mmHg、脉压(62.5±7.6)比(68.3±7.2)mmHg;B组收缩压(145.8±10.1)比(158.7±6.3)mmHg、舒张压(83.7±8.8)比(91.3±6.5)mmHg、脉压(61.7±7.3)比(69.2±8.5)mmHg;均P<0.05],组间相比差异无统计学意义(P>0.05)。A组时期达标率为90.0%,B组时期达标率为91.2%;入组24周与入组时同组相比,两组LVMI、颈动脉IMT及斑块总积分、尿白蛋白与肌酐比值的差异均有统计学意义(P<0.05),组间相比差异无统计学意义(P>0.05);血生化指标组内及组间相比差异无统计学意义(P>0.05);但A组血钾有所下降,B组心率有所升高。结论 2种SPC在老年高血压患者中的应用有效、安全,都可以改善靶器官亚临床病变,各有其优势。     

Role of ACE Inhibitors in treating hypertensive diabetic patients

Cardiovascular disease (CVD) is a major determining factor of morbidity and mortality in type 2 diabetic patients. Hypertension, which accompanies diabetes in more than 70% of cases, contributes to increased prevalence of CVD events in this group of patients. Results from the United Kingdom Prospective Diabetes Study (UKPDS) indicated that reduction of elevated blood pressure might decrease CVD morbidity and mortality more than reduction of hyperglycemia. Activation of circulating and tissue renin-angiotensin system (RAS) contributes to the development of both hypertension and insulin resistance in patients with the cardiometabolic syndrome. Angiotensin-converting enzyme (ACE) inhibitor therapy in patients with the cardio-metabolic syndrome may improve insulin action as well as lessen CVD. In clinical trials, ACE inhibitors have been shown to be more efficient than other antihypertensive medications (ie, calcium channel blockers) in the reduction of CVD morbidity and mortality in hypertensive diabetics. In this article, we summarize possible mechanisms by which ACE inhibition may improve insulin resistance, coagulation/ clotting, and vascular function abnormalities, and postpone or even prevent the development of type 2 diabetes in hypertensive patients.     

Comparison of the effects of four ACE inhibitors on sympathetic reactivity to cold pressor test in essential hypertensive patients

Background. We compared the effects of four different structural angiotensin-converting enzyme (ACE) inhibitors on the hemodynamic profile and catecholamine response to the cold pressor test (CPT) in hypertensive patients. Methods. We studied 44 patients with mild to moderate essential hypertension. The patients were divided into four groups according to the ACE inhibitor [enalapril (E), fosinopril (F), captopril (C), or ramipril (R)]. They were given for 8 weeks. Sympathetic reactivity was evaluated by a CPT at baseline and at the end of therapy. Blood pressure (BP), heart rate (HR), and plasma norepinephrine (NE, pg ml⁻¹) were measured at the times 0, 2, 4, 6, 8, 10, and 15 min. The delta (subtracting the basal values from the min 2 values) and the area under the curve (AUC) of the response during the CPT were studied. Results. The rise in diastolic blood pressure (DBP) (AUC) during the cold stimulus was significantly attenuated by all inhibitors studied (P<0.01): E, 17±22 to 0±20; F, 23±41 to −4±40; C, 34±33 to 7±28; R, 32±28 to −1±25. Drug therapy also blunted the response of HR to cold stress (delta HR, bpm): E, 2±2 to 0±2, P<0.05; F, 2±2 to 0±2, P<0.05; C, 3±3 to −1±3, P<0.01; R, 2±4 to −2±3, P<0.05. The rise in plasma NE (AUC) during CPT was decreased by all ACE inhibitors: E, 198±405 to 24±148, P<0.05; F, 353±436 to 51±412, P<0.05; C, 315±318 to 124±516, P<0.05; R, 677±398 to 251±307, P<0.01. Conclusions. The results in our study suggest that the blunting effects of ACE inhibitors on adrenergic tone seem to be class-dependent.     

ACE inhibitors for the treatment of myocardial ischemia?

Summary Apart from their established use in the treatment of hypertension and heat failure, ACE inhibitors have been suggested to exert anti-ischemic effects. This article reviews the mechanisms of systemic and intracardiac angiotensin formation, as well as its interaction with the bradykinin, the prostaglandin, and the sympathetic nervous system. While high doses of angiotensin can precipitate myocardial ischemia, experimental data on a potential beneficial effect of ACE inhibitors on ischemic myocardial blood flow and function are inconsistent and controversial. Pooling the few available clinical data, several ACE inhibitors may attenuate myocardial ischemia at rest and during exercise. However, a significant fraction of patients does not benefit or even deteriorates. Recent experimental studies suggest a beneficial role of ACE inhibitors in attenuating reperfusion arrhythmias and postinfarction left ventricular remodeling. Unless the mechanisms and determinants of potential anti-ischemic actions of ACE inhibitors can be better defined, their use for treatment of myocardial ischemia cannot be recommended at present.     

Usefulness of ARBs and ACE inhibitors in the prevention of vascular dementia in the elderly

Hypertension is a leading risk factor for vascular dementia. With the increasing burden of dementia, prevention and delay of cognitive decline are becoming a priority. Recent clinical trials have demonstrated that patients taking antihypertensive medications have a reduced incidence of dementia and cognitive impairment. Calcium channel blockers, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers appear to offer significant neuroprotection, even beyond blood pressure reduction. Evidence is emerging that the angiotensin receptor blockers offer superior neuroprotection. This finding has been attributed to the unique property of sustained blockade of the AT1 receptor, combined with simultaneous activation of the AT2 receptors. The use of angiotensin receptor blockers as first-line therapy for hypertension and cognitive protection in the elderly should be strongly considered.     

The differences between ACE inhibitor-treated and calcium channel blocker-treated hypertensive patients

Large-scale outcome trials have demonstrated that blood pressure reduction with angiotensin-converting enzyme (ACE) inhibitors or calcium channel blockers (CCBs) is associated with reduced cardiovascular complications in hypertension. Comparative trials against conventional drugs and between ACE inhibitors and CCBs have failed to reveal conclusive differences in cause-specific outcomes. Studies in high-risk patients suggest that ACE inhibitors are superior to CCBs and other drugs in protection against cardiovascular events and renal disease. Very long-term prospectively collected observational data from the Glasgow Blood Pressure Clinic and the UK General Practice Research Database strongly support an advantage of ACE inhibitors over CCBs for cardiovascular morbidity and mortality. Considering all the available information, it can be concluded that the use of CCBs in the routine therapy of hypertension cannot be recommended while wider use of ACE inhibitors, along with low-dose diuretics and β blockers, appears justified.     

老年高血压合并衰弱患者降压治疗的研究进展

高血压是影响老年人健康的重要因素,降压治疗可降低老年高血压患者脑卒中、心血管事件和死亡等风险。老年人群中衰弱常与高血压并存,但目前关于老年高血压与衰弱的研究相对较少,尤其是老年高血压合并衰弱的降压治疗研究结论不一。老年高血压合并衰弱患者降压治疗的起始值与目标值、衰弱老年人能否从降压治疗中获益以及降压治疗方案的选择等仍争议较大。因此,本文对老年高血压患者合并衰弱的降压治疗进行综述。