Use of angiotensin-converting enzyme inhibitors and variations in cognitive performance among patients with heart failure.

AIMS: Cognitive dysfunction is a prevalent condition among patients with heart failure, and is independently associated with disability and mortality. Angiotensin-converting enzyme (ACE)-inhibitors might increase cerebral blood flow in subjects with heart failure. Our aim was to assess whether starting treatment with ACE-inhibitors might improve cognition in patients with heart failure. METHODS AND RESULTS: Analyses involved 12 081 subjects, 1220 of whom had a verified diagnosis of heart failure, enrolled in a multi-centre pharmaco-epidemiology survey. None of these participants received ACE-inhibitors before hospitalization. Among participants with heart failure, cognitive performance improved in 30% of 446 participants who started ACE-inhibitors, but only in 22% of remaining patients (P=0.001). Among participants without heart failure, cognition improved in 19% of those receiving ACE-inhibitors, and in 18% of untreated patients (P=0.765). Use of ACE-inhibitors among patients with heart failure was associated with improving cognition (odds ratio=1.57; 95% CI 1.18-2.08) also in the multivariable regression modelling, independently of baseline or discharge blood pressure levels. The probability of improving cognitive performance was higher for dosages above the median values, as compared with lower doses (odds ratios=1.90 and 1.42; P for trend=0.001), and increased with duration of treatment (odds ratios for the lower, middle, and upper tertiles=1.25, 1.34, and 1.59; P for trend=0.007). CONCLUSION: Treatment with ACE-inhibitors might selectively improve cognitive performance in patients with heart failure. However, up-titration of these agents might be required to yield the greatest benefit.     

Nitrates versus angiotensin-converting enzyme inhibitors for congestive heart failure

The efficacy of nitrates versus that of angiotensin-converting enzyme (ACE) inhibitors in heart failure may be evaluated based on 3 treatment aims: hemodynamic improvement, symptom relief, and survival benefit. Nitrates used in conjunction with hydralazine produce a relatively large increase in stroke volume and a prominent reduction of left ventricular filling pressure, whereas ACE inhibitors produce a comparatively modest increase in stroke volume with a prominent reduction in filling pressure. The effect of these drugs on arterial compliance has been evaluated using a modified Windkessel model of the circulation to define their mechanism of action. Nitrates appear to affect the large arteries and arterial bed as well as the venous circulation. Intermediate-term response to therapy is often evaluated by changes in exercise tolerance. A review of multicenter trials reveals that, although both ACE inhibitors and hydralazine/nitrate have favorable hemodynamic actions, the effect of hydralazine/nitrate on exercise capacity appears to be slightly better. ACE inhibitors and nitrates both may reduce dysfunctional myocardial remodeling, as evaluated in a canine model of chronic left ventricular dysfunction. The increase in the ejection fraction by these drugs and the decrease of plasma norepinephrine levels by ACE inhibitors may contribute to improved long-term survival. It appears, therefore, that the long-term benefits of nitrates and ACE inhibitors in heart failure probably relate to their ability both to affect cardiac remodeling and to relax vascular smooth muscle.     

The use of angiotensin-converting enzyme inhibitors in congestive heart failure

Summary The development of angiotensin-converting enzyme (ACE) inhibitors has been important in furthering our understanding of the pathophysiology of congestive heart failure and improving the care of these patients. ACE inhibitors have been shown to improve the longevity and quality of life of patients with congestive heart failure. They decrease neurohumoral over-activation, they restore baroreceptor reactivity, and in many cases they increase sodium and water excretion. If hypovolemia and an excessive decrease in renal perfusion pressure can be avoided, ACE inhibitors generally do not cause a deterioration of renal function and may even improve it. By decreasing myocardial metabolic demand, ACE inhibitors appear to have generally beneficial effects on myocardial metabolic balance. At low perfusion pressures, they also appear to maintain cerebral blood flow.     

Utilization and dosing of angiotensin-converting enzyme inhibitors for heart failure

To determine if physician specialty is associated with underutilization and underdosing of angiotensin-converting enzyme inhibitors among patients with heart failure, we reviewed the charts of 214 outpatients with decreased systolic function at an urban academic medical center. Regardless of whether patients were cared for by cardiologists, generalist physicians, or a combination of the two specialties, approximately 75% of the patients were taking an angiotensin-converting enzyme inhibitor. However, only approximately 60% of these patients were taking dosages proved to be efficacious in trials. Emphasis on adequate dosing is needed among all specialty groups.
KEY WORDS: angiotensin-converting enzyme (ACE) inhibitor; congestive heart failure; physician behavior; specialty; quality of care.     

血管紧张素转换酶抑制剂对慢性心力衰竭患者认知功能障碍的改善作用

目的探讨血管紧张素转换酶抑制剂(ACEI)对慢性心力衰竭(CHF)伴认知功能障碍患者认知功能的改善作用。方法选取2017年9月年至2019年2月江苏省荣军医院住院治疗及无锡市山北街道合并认知功能障碍的CHF患者60例,采用随机数表法将患者分为治疗组和对照组,各30例。对照组患者的治疗包括病因治疗、去除诱因、改善心力衰竭等传统疗法,治疗组在对照组基础上给予ACEI治疗。分别采用蒙特利尔认知评估量表(MoCA)、汉密顿焦虑量表(HAMA)和汉密顿抑郁量表(HAMD)分别评估患者的认知功能、焦虑和抑郁状况。采用SPSS 21.0统计软件分析数据。结果干预前,2组患者MoCA各项评分及总分比较,差异均无统计学意义(P0.05)。干预后,与对照组相比,治疗组患者MoCA各项评分均有所增加,其中视空间及执行能力[(4.27±0.52)vs(2.70±0.54)分]和总分值[(24.70±1.09)vs(22.23±1.43)分]差异有统计学意义(P0.01)。与干预前比较,治疗组干预后各项MoCA评分均增加,其中总分[(24.70±1.09)vs(22.60±1.54)分]和视空间及执行能力[(4.27±0.52)vs(2.77±0.68)分]差异有统计学意义(P0.05)。干预前及干预后,2组患者间心功能、左室射血分数、焦虑、抑郁评分比较差异均无统计学意义(P0.05);各组干预前后上述指标比较差异亦无统计学意义(P0.05)。治疗期间2组患者心功能始终处于稳定状态,均未诱发急性心功能衰竭,药物治疗种类及方案也未调整。2组患者均未出现严重不良反应,亦未出现新的合并症。结论 ACEI类药物能够改善CHF患者的认知功能,提高患者的执行能力。     

Importance of long-acting angiotensin-converting enzyme inhibitors for congestive heart failure.

The renin-angiotensin system (RAS) has both localized and systemic effects in the pathophysiology of heart failure. These may lead to structural changes in the heart and blood vessels as well as to more disseminated symptomatology, including vasoconstriction and both salt and water retention. In association with other neurohormonal mechanisms, such as the sympathetic nervous system, these latter effects result in an elevated work load for the heart. The increase in neurohormonal activity, seen in some patients with heart failure, may result in a loss of circadian variation in heart rate and blood pressure and deprive the heart of a needed reduction in work load during the night. The suppression of such neurohormonal activity through the use of long-acting angiotensin-converting enzyme (ACE) inhibitors, such as lisinopril, provides a means of controlling such symptoms. In comparison with short-acting ACE inhibitors, such long-acting suppression of the RAS may have a number of advantages. These include a more sustained increase in exercise duration, improvement in left ventricular ejection fraction, and, speculatively, a better influence on patient mortality.     

Role and optimal dosing of angiotensin-converting enzyme inhibitors in heart failure

Based on overwhelming data demonstrating reduced morbidity and mortality, ACE inhibitors form a mainstay of therapy in all patients with symptomatic left ventricular systolic dysfunction. Furthermore, ACE inhibitors may be beneficial in the prevention of heart failure in patients with high-risk cardiovascular profiles. However, definite benefit from the use of ACE inhibitors in all patients with heart failure and preserved ejection fraction has not been demonstrated. Even though ACE inhibitors probably have a class effect in patients who have heart failure, it is recommended that ACE inhibitors that have been shown to reduce morbidity and mortality in clinical trials (captopril, enalapril, lisinopril, and ramipril) be used because studies have clearly defined a dose for these agents that is effective in modifying the natural history of the disease. Attempts should be made to up titrate patients to target doses of ACE inhibitors that have been used in clinical trials, if tolerated.     

Aldosterone antagonism in addition to angiotensin-converting enzyme inhibitors in heart failure

Although the role of the systemic renin-angiotensin-aldosterone system in the pathophysiology of heart failure is well-known for years, the impact of a local cardiac aldosterone system has been recognized recently. Aldosterone promotes cardiac hypertrophy and fibrosis in hypertension and heart failure and is involved in left ventricular remodeling after myocardial infarction. Plasma aldosterone levels in patients with heart failure are an indicator of a worse prognosis. Although ACE inhibitor therapy in these patients reduces plasma aldosterone levels, this effect is only transitory, a phenomenon referred to as "aldosterone escape". Even maximally recommended doses of ACE inhibitors do not completely prevent ACE-mediated formation of angiotensin II in chronic heart failure, and those patients with increased aldosterone levels during ACE inhibition have impaired exercise capacity. The RALES study has demonstrated convincingly that in patients with heart failure, addition of the mineralocorticoid receptor antagonist spironolactone (25 mg/d) to ACE inhibition markedly reduces mortality and prevents worsening heart failure. While reduction of excessive extracellular matrix turnover leading to decreased fibrosis appears to be the most important effect of spironolactone in heart failure, other mechanisms such as regression of hypertrophy, improvement of endothelial function, enhanced renal sodium excretion and antiarrhythmic actions may contribute. In RALES, low-dose spironolactone did not confer a substantial risk of hyperkalemia, however, with broader use of spironolactone in heart failure, cases of hyperkalemia associated with the use of this drug increase. Close control of serum potassium and creatinine and estimation of creatinine clearance are mandatory, especially in the presence of additional factors impairing renal function. The new and more selective aldosterone antagonist eplerenone which is devoid of some side effects of spironolactone, has been shown to be effective in hypertension and holds great promise as future therapeutic agent in patients with heart failure.     

Effect of angiotensin-converting enzyme inhibitors on endothelium-dependent peripheral vasodilation in patients with chronic heart failure

Objectives. This study was performed to determine whether acute inhibition of angiotensin-converting enzyme restores impaired endothelium-dependent vasorelaxation in patients with chronic heart failure.Background. Recent reports have demonstrated that endothelium-dependent vasodilation induced by cholinergic stimuli is attenuated in the peripheral vascular bed of patients with chronic heart failure.Methods. We examined the effects of local intraarterial infusion of enalaprilat (0.6 μg/min per 100 ml tissue volume) on responses inflated by acetylcholine or sodium nitroprusside in the forearm vascular bed in 8 normal subjects, 12 patients with mild heart failure (New York Heart Association functional classes I and II) and 10 patients with more advanced heart failure (functional classes III and IV). Forearm blood flow was measured by means of venous occlusion plethysmography.Results. Although enalaprilat alone did not affect basal forearm blood flow, it significantly augmented the increase in forearm blood flow induced by acetylcholine in normal subjects (p < 0.01) and in those with mild heart failure (p < 0.05). However, the effect was not found in patients with more advanced heart failure. Coinfusion of enalaprilat did not enhance sodium nitroprussideinduced vasodilation in any of the groups. To explore the mechanism of the inhibitor's effect, an additional 20 patients with mild heart failure (functional class II) were pretreated with a cyclooxygenase inhibitor, acetylsalicylic acid (n = 10) or an inhibitor of nitric oxide synthesis, N^G-monomethyl-l-arginine (n = 10), followed by administration of acetylcholine with or without enalaprilat. Acetylsalicylic acid reduced the converting enzyme inhibitor's effect, whereas N^G-monomethyl-l-arginine failed to block tie augmentation of blood flow.Conclusions. These results suggest that inhibition of angiotensinconverting enzyme potentiates endothelium-dependent vasodilation induced by cholinergic stimuli, presumably through modulation of prostaglandin metabolism, in the peripheral vasculature of patients with mild chronic heart failure.     

Comparison of angiotensin-converting enzyme inhibitors in the treatment of congestive heart failure

The effectiveness of the different angiotensin-converting enzyme (ACE) inhibitors in the treatment of patients with congestive heart failure (CHF) was compared by performing a retrospective cohort study using linked administrative databases on elderly patients admitted to the hospital for the treatment of CHF. Relative to those initiated on enalapril, no significant differences in the combined end point of readmission to the hospital for CHF or mortality were observed among users of lisinopril, ramipril, or other ACE inhibitors. In terms of effectiveness for the treatment of patients with CHF, the findings of this study suggest a class effect among ACE inhibitors.     

Anti-oxidative properties of beta-blockers and angiotensin-converting enzyme inhibitors in congestive heart failure

BACKGROUND: Chronic elevation of plasma catecholamines and sympathetic stimulation in chronic heart failure (CHF) leads to increased production of free radicals, and so possibly to endothelial damage/dysfunction and atheroma formation. Abnormal oxidative stress may therefore be related to some of the high mortality and morbidity in CHF. The objective of the present prospective open study was to compare the effects of beta-blockers and ACE inhibitors in relation to oxidative stress and endothelial damage in CHF. METHODS: We studied 66 outpatients with CHF: 46 patients were established on an ACE inhibitor and were then started on a beta-blocker, and 20 patients not previously on ACE-inhibitors were started on lisinopril. Baseline levels of the measured parameters were compared to 22 healthy control subjects. Serum lipid hydroperoxides (LHP) and total antioxidant capacity (TAC) were determined as indices of oxidative damage and antioxidant defence, and plasma von Willebrand factor (vWf) as an index of endothelial damage/dysfunction. RESULTS: Baseline indices for the measures of oxidative damage and endothelial function in the 66 CHF patients were significantly higher than healthy control subjects [median LHP 7.5 (5.9-12.6) vs. 4.8 micromol/l, P=0.0022; TAC 428 (365-567) vs. 336 Trollox Eq. Units, P=0.0005; mean vWf 134+/-27 vs. 89+/-23 IU/dl, P<0.0001]. Following 3 months of maintenance therapy with beta-blockers, there was significant reduction in LHP levels, but not TAC or vWf. ACE inhibitor therapy also significantly reduced vWf levels, but failed to have any statistically significant effects on LHP or TAC. CONCLUSION: This pilot study suggests that oxidative stress in CHF may be due to increased free radical production or inefficient free radical clearance by scavengers. beta-Blockers, but not ACE inhibitors, reduced lipid peroxidation in patients with CHF. No relation was demonstrated between a reduction in oxidative damage and endothelial damage/dysfunction.