Role Of Angiotensin-converting Enzyme Inhibitors Research Articles

COVID-19 and Cardiovascular Disease.

Coronavirus disease 2019 (COVID-19) is a global pandemic affecting 185 countries and >3 000 000 patients worldwide as of April 28, 2020. COVID-19 is caused by severe acute respiratory syndrome coronavirus 2, which invades cells through the angiotensin-converting enzyme 2 receptor. Among patients with COVID-19, there is a high prevalence of cardiovascular disease, and >7% of patients experience myocardial injury from the infection (22% of critically ill patients). Although angiotensin-converting enzyme 2 serves as the portal for infection, the role of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers requires further investigation. COVID-19 poses a challenge for heart transplantation, affecting donor selection, immunosuppression, and posttransplant management. There are a number of promising therapies under active investigation to treat and prevent COVID-19.

Anaemia in heart failure patients: the prevalence of haematinic deficiencies and the role of ACE inhibitors and aspirin doses as risk factors.

Background:Patients with heart failure often have comorbidities that alter the progression of heart failure and impact on prognosis. One such comorbidity is anaemia, and clinicians have started to appreciate the full gravity of its impact on heart failure patients. Yet, the extent of the problem is not fully understood, particularly the role of heart failure therapy itself as a risk factor for developing anaemia.Objective:This study aimed to investigate the prevalence of anaemia in a cohort of heart failure patients. The impact of using different ACEIs and different doses of aspirin was also explored, together with the prevalence of haematinic deficiencies.Methods:Medication lists and pathology results were examined to establish the prevalence of ACEIs use, and the use of aspirin at its most common doses of 100mg and 150mg, together with haematinic deficiencies. Multinomial logistic regression and the Student’s t-test were utilised for the analysis of data. Statistical significance was pre-set at p<0.05.Results:Ninety-six patients were eligible for analysis, with 26% having anaemia. The use of ACEIs had a RR of 17.4 for the presence of anaemia. Perindopril was associated with a RR of 20.8, while the use of ramipril was not significantly associated with such a high RR. Haematinic anaemia occurred only at a rate of 3.3%, but borderline deficiencies were found in more than a third of all patients. An aspirin dose of 150mg was associated with a higher risk for anaemia, compared to a dose of 100mg.Conclusions:ACEIs are associated with the presence of anaemia, with perindopril posing more risk than ramipril when used in heart failure patients. The dose of aspirin may also be a factor in the development of anaemia, with lower doses being safer. Despite the lack of high prevalence of haematinic anaemia among this cohort of patients, borderline haematinic deficiencies were common.

The role of ACE inhibitors in cardiovascular disease

Cardiovascular disease is the leading cause of death in the UK, with heart failure and ischaemic heart disease the commonest forms of the condition. The renin–angiotensin–aldosterone system is recognised as having an integral pathophysiological role by increasing afterload, promoting sodium and water retention and contributing to ventricular remodelling. Evidence from randomised controlled trials has demonstrated that angiotensin-converting enzyme (ACE) inhibitors reduce mortality, slow disease progression and reduce left ventricular workload. This is achieved by inhibiting the conversion of angiotensin I to angiotensin II. Preload and afterload are reduced, which preserves left ventricular function. Common adverse effects include cough, hypotension, hyperkalaemia and a decline in renal function. The nurses' role in caring for patients receiving ACE inhibitor therapy includes clinical assessment, monitoring and detecting adverse effects as well as patient education.

Age- and Genotype-Specific Effects of the Angiotensin-Converting Enzyme Inhibitor Lisinopril on Mitochondrial and Metabolic Parameters in Drosophila melanogaster.

The angiotensin-converting enzyme (ACE) is a peptidase that is involved in the synthesis of Angiotensin II, the bioactive component of the renin-angiotensin system. A growing body of literature argues for a beneficial impact of ACE inhibitors (ACEi) on age-associated metabolic disorders, mediated by cellular changes in reactive oxygen species (ROS) that improve mitochondrial function. Yet, our understanding of the relationship between ACEi therapy and metabolic parameters is limited. Here, we used three genetically diverse strains of Drosophila melanogaster to show that Lisinopril treatment reduces thoracic ROS levels and mitochondrial respiration in young flies, and increases mitochondrial content in middle-aged flies. Using untargeted metabolomics analysis, we also showed that Lisinopril perturbs the thoracic metabolic network structure by affecting metabolic pathways involved in glycogen degradation, glycolysis, and mevalonate metabolism. The Lisinopril-induced effects on mitochondrial and metabolic parameters, however, are genotype-specific and likely reflect the drug’s impact on nutrient-dependent fitness traits. Accordingly, we found that Lisinopril negatively affects survival under nutrient starvation, an effect that can be blunted by genotype and age in a manner that partially mirrors the drug-induced changes in mitochondrial respiration. In conclusion, our results provide novel and important insights into the role of ACEi in cellular metabolism.

Role of ACE inhibitors in anthracycline-induced cardiotoxicity: A randomized, double-blind, placebo-controlled trial.

Several measures including drugs have been tried to reduce anthracycline cardiotoxicity. The lack of randomized trials prompted this study to assess the role of an angiotensin converting enzyme (ACE) inhibitor (enalapril) in anthracycline-induced cardiotoxicity in children with hematological malignancies. A randomized, double-blind, placebo-controlled trial was conducted on 84 patients with leukemia (41) and lymphoma (43) who received anthracyclines (doxorubicin and/or daunorubicin) at cumulative dose ≥200mg/m2 . The patients were randomized to receive either enalapril [group A (n=44)] or placebo [group B (n=40)] for 6months. Left ventricular ejection fraction (LVEF) and cardiac biomarkers (cardiac troponin I [cTnI], probrain natriuretic peptide [proBNP], and creatine kinase MB [CK-MB]) were assessed at baseline and 6months. The primary outcome was a measured decrease in LVEF (≥20%). Secondary outcome measures were changes in cardiac biomarkers and the development of heart failure or arrhythmias. LVEF decreased in both groups at 6months, more so in group B (62.25±5.49vs 56.15±4.79, P<0.001). A ≥20% decrease was seen in 3 patients in group B but none in group A (P=0.21). Cardiac biomarkers increased more in group B at 6months, and the increase was significant for proBNP (49.60±35.97vs 98.60±54.24, P<0.001) and cTnI (0.01±0.00vs 0.011±0.003, P=0.035) but not significant for CK-MB (1.08±0.18vs 1.21±0.44, P=0.079). In group A, 9.1% of the patients showed an increase in proBNP level ≥100 compared with 37.5% in group B (P<0.001). No patient developed heart failure or arrhythmia. Enalapril has a role in reducing cardiac toxicity after anthracycline administration.

The Role of Angiotensin-Converting Enzyme Inhibitors in Patients with Chronic Subdural Hematoma: A Scandinavian Population-Based Multicenter Study.

To investigate the role of angiotensin converting enzyme (ACE) inhibitors in the recurrence of chronic subdural hematoma (cSDH) after burr hole surgery. A retrospective review was conducted of a Scandinavian multicenter, population-based cohort of 1252 adults with cSDH who underwent with burr hole surgery between January 1, 2005, and December 31, 2010. The risk of cSDH recurrence was assessed in users of ACE inhibitors, users of angiotensin II receptor blockers (ARBs), and those without ACE inhibitor treatment (no ACE inhibitor group) using univariable and multivariable regression analyses. The cohort included 98 (7.8%) ACE inhibitor users and 63 (5%) ARB-only users. The recurrence rate was 16.3% (n= 16) in the ACE inhibitor group, compared with 13.3% (n= 153) in the no ACE inhibitor group (P= 0.39) and 14.3% (n= 9) in the ARB group (P= 0.73). When comparing groups, age (P= 0.01), Charlson Comorbidity Index (P= 0.01), use of platelet inhibitors (P= 0.001) and use of anticoagulants (P= 0.01) differed between the ACE inhibitor and no ACE inhibitor groups. Only age differed significantly between the ACE inhibitor and ARB groups (P= 0.03). In the analyses adjusted for differences in baseline characteristics, ACE inhibitor treatment did not influence the risk of recurrence (odds ratio, 1.2; 95% confidence interval, 0.7-2.2; P= 0.46). In this population-based study, the use of ACE inhibitors was not associated with the risk of recurrence following burr hole surgery for cSDH.

Effects of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers on cardiovascular events and residual renal function in dialysis patients: a meta-analysis of randomised controlled trials

BackgroundThe role of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) reducing risk of cardiovascular events (CVEs) and preserving kidney function in patients with chronic kidney disease is well-documented. However, the efficacy and safety of these agents in dialysis patients is still a controversial issue.MethodsWe systematically searched MEDLINE, Embase, Cochrane Library and Wanfang for randomized trials. The relative risk (RR) reductions were calculated with a random-effects model. Major cardiovascular events, changes in GFR and drug-related adverse events were analyzed.ResultsEleven trials included 1856 participants who were receiving dialysis therapy. Compared with placebo or other active agents groups, ARB therapy reduced the risk of heart failure events by 33% (RR 0.67, 95% CI 0.47 to 0.93) with similar decrement in blood pressure in dialysis patients. Indirect comparison suggested that fewer cardiovascular events happened during treatment with ARB (0.77, 0.63 to 0.94). The results indicated no significant differences between the two treatment regimens with regard to frequency of myocardial infarction (1.0, 0.45 to 2.22), stroke (1.16, 0.69 to 1.96), cardiovascular death (0.89, 0.64 to 1.26) and all-cause mortality (0.94, 0.75 to 1.17). Five studies reported the renoprotective effect and revealed that ACEI/ARB therapy significantly slowed the rate of decline in both residual renal function (MD 0.93 mL/min/1.73 m2, 0.38 to 1.47 mL/min/1.73 m2) and urine volume (MD 167 ml, 95% CI 21 ml to 357 ml). No difference in drug-related adverse events was observed in both treatment groups.ConclusionsThis study demonstrates that ACE-Is/ARBs therapy decreases the loss of residual renal function, mainly for patients with peritoneal dialysis. Overall, ACE-Is and ARBs do not reduce cardiovascular events in dialysis patients, however, treatment with ARB seems to reduce cardiovascular events including heart failure. ACE-Is and ARBs do not induce an extra risk of side effects.

Effect of Renin-Angiotensin System Blockage in Patients with Acute Respiratory Distress Syndrome: A Retrospective Case Control Study.

Background Acute respiratory distress syndrome (ARDS) remains a life-threatening disease. Many patients with ARDS do not recover fully, and progress to terminal lung fibrosis. Angiotensin-converting enzyme (ACE) inhibitor is known to modulate the neurohormonal system to reduce inflammation and to prevent tissue fibrosis. However, the role of ACE inhibitor in the lungs is not well understood. We therefore conducted this study to elucidate the effect of renin-angiotensin system (RAS) blockage on the prognosis of patients with ARDS.Methods We analyzed medical records of patients who were admitted to the medical intensive care unit (ICU) at a tertiary care hospital from January 2005 to December 2010. ARDS was determined using the Berlin definition. The primary outcome was the mortality rate of ICU. Survival analysis was performed after adjustment using propensity score matching.Results A total of 182 patients were included in the study. Thirty-seven patients (20.3%) took ACE inhibitor or angiotensin receptor blocker (ARB) during ICU admission, and 145 (79.7%) did not; both groups showed similar severity scores. In the ICU, mortality was 45.9% in the RAS inhibitor group and 58.6% in the non-RAS inhibitor group (P = 0.166). The RAS inhibitor group required a longer duration of mechanical ventilation (29.5 vs. 19.5, P = 0.013) and longer ICU stay (32.1 vs. 20.2 days, P < 0.001). In survival analysis, the RAS inhibitor group showed better survival rates than the non-RAS group (P < 0.001).Conclusions ACE inhibitor or ARB may have beneficial effect on ARDS patients.

Intensity of hydration changes the role of renin-angiotensin-aldosterone system blockers in contrast-induced nephropathy risk after coronary catheterisation in patients with chronic kidney disease.

Objective:This study evaluated the potential effect of hydration intensity on the role of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) on contrast-induced nephropathy in patients with renal insufficiency.Methods:All eligible patients were included and stratified according to hydration intensity defined as saline hydration volume to body weight tertiles: <10.21 mL/kg, 10.21 to <17.86 mL/kg, and ⩾17.86 mL/kg.Results:In total, 84 (6.7%) of 1254 patients developed contrast-induced nephropathy: 6.2% in the ACEI/ARB group versus 10.8% in the non-ACEI/ARB group (P=0.029), with an adjusted odds ratio (OR) of 0.89 (95% confidence interval (CI) 0.46–1.73, P=0.735). The incidence of contrast-induced nephropathy was lower in the ACEI/ARB group than in the non-ACEI/ARB group in the second tertile (P=0.031), while not significantly different in the first (P=0.701) and third (P=0.254) tertiles. ACEIs/ARBs were independently associated with a lower contrast-induced nephropathy risk (OR 0.26, 95% CI 0.09–0.74, P=0.012) and long-term all-cause death (hazard ratio 0.461, 95% CI 0.282–0.755, P=0.002) only in the second hydration volume to body weight tertile.Conclusion:The effects of ACEIs/ARBs on contrast-induced nephropathy risk vary according to saline hydration intensity in chronic kidney disease patients, and may further reduce contrast-induced nephropathy risk in patients administered moderate saline hydration.

Banting Memorial Lecture 2016 Reducing lifetime risk of complications in adolescents with Type 1 diabetes.

Adolescence is a challenging period of life for any young person, and for those with Type 1 diabetes, physiological and psychological factors can result in a deterioration in glycaemic control. In young people with Type 1 diabetes, puberty may be an additional risk factor impacting on the lifetime risk for renal and cardiovascular complications. Our longitudinal studies have identified that increases in urinary albumin excretion through childhood are associated with the development of microalbuminuria and a generalized endotheliopathy linked to cardiovascular risk. Screening of participants recruited to the Adolescent type 1 Diabetes cardio-renal Intervention Trial (AdDIT) confirms that these early changes in albumin excretion are related to both diabetic nephropathy and cardiovascular risk; in part, independent of glycaemic control. Thus, as well as current attempts to improve glycaemic control through enhanced targeted insulin delivery, pumps, sensors and closed loop, we have explored the role of angiotensin-converting enzyme inhibitors and statins in providing cardio-renal protection during adolescence.

Angioneuroticus oedema előfordulása ischaemiás stroke miatt rt-PA-val kezelt betegekben

Data of our 254 patients who were treated with rt-PA between 1st of Jan, 2011 and 31st of Dec, 2014 were processed. We focused on angioneurotic oedema as allergic complication of thrombolysis which caused life threatening respiratory obstruction in two cases. We describe these two patients' history. Out of 254 patients six (2.3%) suffered angioneurotic edema caused respiratory obstruction in two (0.90%) cases. This occurrence is approximately 1.3-5.1% in literature. Five, out of six patients who suffered from angioneurotic oedema, had been treated with ACE inhibitors or ARB before. The role of ACE inhibitors is known in metabolism of bradykinin cascade. Plasmin which present during thrombolysis, precipitates biochemical mechanisms of this potential life threatening complication. Therefore rt-PA alone can be the cause of angioedema, but it can be more frequent together with ACE inhibitors therapy.

Hypertension in type 2 diabetes mellitus: effect of the disease and treatment on development of peripheral artery disease

Coexistence of diabetes and hypertension is well known so as their role as a risk factor for vasculopathy of lower limbs. Ankle brachial index (ABI) offers a simple, fairly reliable mean to quantify this problem. Very few studies in India have assessed the role of angiotensin-converting enzyme inhibitors (ACEI) in preventing vasculopathy in type 2 diabetics. A heterogeneous representative sample of 149 type 2 diabetics (103 ACEI user and 46 non-ACEI user) taking regular pharmacotherapy was tested by ABI using vascular Doppler to assess peripheral artery disease (PAD) following standard protocol. Distribution of risk factors for PAD and ABI values were compared between ACEI user and non-ACEI user diabetics. ABI ≤0.9 was defined as PAD and P value 0.9) than non-ACEI user diabetics. The non-ACEI user diabetics did not show statistically significant lower ABI difference. But by defining ABI ≤0.9 as PAD, type 2 diabetics not using ACEI proved to be at 2.12 times risk (OR to develop PAD) than those receiving it. Type 2 diabetic hypertensives taking ACEI with strict blood pressure control have an added benefit against PAD along with other established benefits, and the same pharmacotherapy may be used in non-ACEI user diabetics to turn secondary prevention into primary one.

Angiotensin II–Converting Enzyme Inhibition Improves Survival, Ventricular Remodeling, and Myocardial Energetics in Experimental Aortic Regurgitation

Aortic valve regurgitation (AR) is a volume-overload disease causing severe eccentric left ventricular (LV) hypertrophy and eventually heart failure. There is currently no approved drug to treat patients with AR. Many vasodilators including angiotensin-converting enzyme inhibitors have been evaluated in clinical trials, but although some results were promising, others were inconclusive. Overall, no drug has yet been able to improve clinical outcome in AR and the controversy remains. We have previously shown in an animal model that captopril (Cpt) reduced LV hypertrophy and protected LV systolic function, but we had not evaluated the clinical outcome. This protocol was designed to evaluate the effects of a long-term Cpt treatment on survival in the same animal model of severe aortic valve regurgitation. Forty Wistar rats with AR were treated or untreated with Cpt (1 g/L in drinking water) for a period of 7 months to evaluate survival, myocardial remodeling, and function by echocardiography as well as myocardial metabolism by µ positron emission tomography scan. Survival was significantly improved in Cpt-treated animals with a survival benefit visible as soon as after 4 months of treatment. Cpt reduced LV dilatation and LV hypertrophy. It also significantly improved the myocardial metabolic profile by restoring the level of fatty acids metabolic enzymes and use. In a controlled animal model of pure severe aortic valve regurgitation, Cpt treatment reduced LV remodeling and LV hypertrophy and improved myocardial metabolic profile and survival. These results support the need to reevaluate the role of angiotensin-converting enzyme inhibitors in humans with AR in a large, carefully designed prospective clinical trial.

Angiotensin-converting enzyme and the tumor microenvironment: mechanisms beyond angiogenesis

The renin angiotensin system (RAS) is a network of enzymes and peptides that coalesce primarily on the angiotensin II type 1 receptor (AT1R) to induce cell proliferation, angiogenesis, fibrosis, and blood pressure control. Angiotensin-converting enzyme (ACE), the key peptidase of the RAS, is promiscuous in that it cleaves other substrates such as substance P and bradykinin. Accumulating evidence implicates ACE in the pathophysiology of carcinogenesis. While the role of ACE and its peptide network in modulating angiogenesis via the AT1R is well documented, its involvement in shaping other aspects of the tumor microenvironment remains largely unknown. Here, we review the role of ACE in modulating the immune compartment of the tumor microenvironment, which encompasses the immunosuppressive, cancer-promoting myeloid-derived suppressor cells, alternatively activated tumor-associated macrophages, and T regulatory cells. We also discuss the potential roles of peptides that accumulate in the setting of chronic ACE inhibitor use, such as bradykinin, substance P, and N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP), and how they may undercut the gains of anti-angiogenesis from ACE inhibition. These emerging mechanisms may harmonize the often-conflicting results on the role of ACE inhibitors and ACE polymorphisms in various cancers and call for further investigations into the potential benefit of ACE inhibitors in some neoplasms.

Carotid Artery Intima-Media Thickness and the Renin-Angiotensin System

Carotid artery intima-media thickness (IMT) is a biomarker for cardiovascular disease that also predicts the risk of cardiovascular mortality. Angiotensin-Converting enzyme (ACE) inhibition is a unique therapeutic modality because it both treats hypertension and improves arterial health and cardiovascular disease outcomes. Controversy exists regarding the role of ACE inhibitors and angiotensin receptor blockers (ARBs) in IMT regression. Our article provides an update on how ACE inhibitors and ARBs could play a role in decreasing IMT.

Prognostic effect of angiotensin-converting-enzyme inhibitors in HCC patients treated with sorafenib.

328 Background: Experimental studies indicated that angiotensin-converting-enzyme inhibitors (ACEs) or angiotensin receptor blockers (ARBs) has a role in reducing malignant changes of the liver and may significantly improve the mortality in patients with other cancers. However it is not known whether ACE and ARB inhibitors may have prognostic impact on HCC survival outcome. We aimed at evaluating the role of ACE inhibitors and ARB blockers on the prognosis of HCC patients who have been treated by Nexavar (sorafenib). Methods: Using resources of our case-control study at MD Anderson, total of 187 (males, 76.5%; females, 23.5%) pathologically confirmed HCC had been treated by sorafenib. The overall mean age (±SD) was 62.5years ± 9.6. The majority of patients were Caucasians (62.6%) who were diagnosed at TNM stage III and IV (79.2%). Total of 89 (47.6%) patients had no evidence of hepatitis C virus (HCV) or hepatitis B virus (HBV). Median survival was calculated using Kaplan Meier product-limit method and survival rates were compared using the log rank test. Cox proportional hazards model was used to estimate the univariate and multivariate Hazard Risk Ratios (HRR) and 95% Confidence Interval (CI). Results: The overall median survival of HCC patients was 19.9 months (95% CI, 16.1-23.6). Intake of ACEs or ARBs inhibitors was reported in 94 patients (50.3%). We observed significant difference in overall median survival (months) between patients who had ACE/ARB inhibitors versus those who did not, median survival (95% CI) were 21.5 (17.1-25.8) and 14.6 (12.4-16.7), respectively, p=0.04. After adjustment for HCC prognostic factors and demographic factors, we observed 30% reduction in HCC mortality among those who received ACEs/ARBs inhibitors, the estimated HR was 0.7 (95% CI, 0.4-1), p=0.05. Conclusions: Our results may indicate that HCC patients under anti-angiogenic therapy (sorafenib) and have been under anti-hypertensive therapy like ACE/ARB may assist in depleting the collagen and may improve host matrix and tumor microenvironment to enhance drug delivery. Future analysis in a larger sample is warranted

Response to 'Ramipril attenuates lipid peroxidation and cardiac fibrosis in an experimental model of rheumatoid arthritis'

We read with great interest the recent issue of Arthritis Research & Th erapy i n which Shi and colleagues [1] investi gated the eff ects of ramipril on oxidative stress and fi brosis in the heart of rat s with adjuvant arthritis. Th e authors concluded that ramipril reversed arthritis scoring and decreased markers of oxidative stress, infl ammation, and tissue fi brosis. Undoubtedly, their fi ndings will promote the attempt to diminish the cardiovascular risk of patients with rheumatoid arthritis (RA) by using angio tensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) or both. However, several important aspects should be considered in the interpretation of this study. As described by the authors, adjuvant arthritis was induced successfully in female rats with a 100% incidence rate, but actually the male rats were use d in most cases [2-4]. Th ere fore, we speculate that this discrepancy may be related to th e impact of arthritis on cardiac fi brosis and oxidative stress status in the heart o f rats with adjuvant arthritis. In addition, the dosage of ramipril is a matter of debate. In a randomized and double-blind clinical study, treatment with 10 mg/day ramipril eff ectively improved endothelial function in patients with RA [5]. Intriguingly, how was the ramipril dosage (10 mg/kg per day) used in this animal study calculated? Unlike previous reports focusing on the eff ect of ramipril and ARBs on vascular function with RA and experimental models [2,5], the article by Shi and colleagues reported that ramipril improved c ardiac function in rats with adjuvant arthritis. Although we list some methodological issues here, we believe that the authors’ fi ndings strongly suggest a promising therapeutic role of ACEIs and ARBs on both card iovascular risk and arthritis in patients with RA.

Residual renal function in hemodialysis patients: the role of Angiotensin-converting enzyme inhibitor in its preservation.

Residual Renal function (RRF) has an important role in the overall morbidity and mortality in hemodialysis patients. The role of angiotensin-converting enzyme inhibitor (ACEi) in preserving renal function in chronic proteinuric nephropathies is well documented. We test the hypothesis that enalapril (an ACEi) slows the rate of decline of RRF in patients starting hemodialysis. A prospective, randomized open-label study was carried out. 42 patients were randomized in two groups either in treatment with enalapril or no treatment at all. Our study has proven that enalapril has a significant effect on preserving residual renal function in patients starting dialysis at least during the first 12 months from the initiation of the hemodialysis. Further studies are necessary in order to investigate the potential long-term effect of ACEi on residual renal function and on morbidity and mortality in patients starting hemodialysis.

Is Microalbuminuria a Disease?

Debate has arisen as to the proper timing of starting angiotensin-converting enzyme (ACE) inhibitor or angiotensin II receptor blocker (ARB) therapy to mitigate nephropathy in patients with diabetes mellitus. In April 2012, an article published in both the Pharmacist’s Letter and the Prescriber’s Letter advocated the withholding of these therapies in patients with diabetes who have microalbuminuria in the absence of hypertension. This practice is contrary to the 2012 American Diabetes Association (ADA) guidelines, which were acknowledged by both the Pharmacist’s Letter and the Prescriber’s Letter. As a past member of the ADA’s Professional Practice Oversight Committee (the committee that updates the ADA guidelines annually) and a current member of the advisory board for both publications (the Pharmacist’s Letter and the Prescriber’s Letter), I thought it would be worthwhile to revisit the data used by these publications to create their recommendation. The debate involves two primary questions: What is the general role of ACE inhibitor or ARB therapy in vascular disease, and when is it appropriate to begin these therapies to slow the progression of nephropathy?

Cognitive Protection by Angiotensin Converting Enzyme Inhibitors in Heart Failure

Cardio-selective medications such as angiotensin converting enzyme (ACE) inhibitor centrally active or non-centrally-active and angiotensin receptor blocker (ARB) have been researched in animals and humans for potential cognitive benefits. This secondary analysis presents results of a published cross sectional study of 90 community-dwelling adults with heart failure (HF) who were screened for cognitive impairment using the Montreal Cognitive Assessment (MoCA). The mean MoCA score was 24.73 (SD 2.76). T-test on the MoCA score and ACE inhibitor (78% of participants) and centrally-active ACE inhibitor (60%) were statistically significant (p= 0.01) with no association to ARBs. Bivariate analysis indicated higher dosages of ACE inhibitors were associated with better cognitive function (R= 0.211, p=0.046) with no association to ARBs. In the multiple regression model, covariates age, education, knowledge on HF medication, and mean arterial blood pressure accounted for 33.6% of variance and ACE inhibitor added 4.1 % of variance and remained statistically significant (p=0.021); age and mean arterial blood pressure were not significant in the final regression model. Findings from this study provided rationale to support the protective role of ACE inhibitors on cognitive decline among HF patients.