Absence Of Angiotensin-converting Enzyme Inhibitors Research Articles

Charlson comorbidity index, neutrophil-to-lymphocyte ratio and undertreatment with renin-angiotensin-aldosterone system inhibitors predict in-hospital mortality of hospitalized COVID-19 patients during the omicron dominant period.

PurposeTo investigate the clinical predictors of in-hospital mortality in hospitalized patients with Coronavirus disease 2019 (COVID-19) infection during the Omicron period.MethodsAll consecutive hospitalized laboratory‐confirmed COVID-19 patients between January and May 2022 were retrospectively analyzed. All patients underwent accurate physical, laboratory, radiographic and echocardiographic examination. Primary endpoint was in-hospital mortality.Results74 consecutive COVID-19 patients (80.0 ± 12.6 yrs, 45.9% males) were included. Patients who died during hospitalization (27%) and those who were discharged alive (73%) were separately analyzed. Compared to patients discharged alive, those who died were significantly older, with higher comorbidity burden and greater prevalence of laboratory, radiographic and echographic signs of pulmonary and systemic congestion. Charlson comorbidity index (CCI) (OR 1.76, 95%CI 1.07-2.92), neutrophil-to-lymphocyte ratio (NLR) (OR 1.24, 95%CI 1.10-1.39) and absence of angiotensin-converting enzyme inhibitors (ACEI)/angiotensin II receptor blockers (ARBs) therapy (OR 0.01, 95%CI 0.00-0.22) independently predicted the primary endpoint. CCI ≥7 and NLR ≥9 were the best cut-off values for predicting mortality. The mortality risk for patients with CCI ≥7, NLR ≥9 and not in ACEI/ARBs therapy was high (86%); for patients with CCI <7, NLR ≥9, with (16.6%) or without (25%) ACEI/ARBs therapy was intermediate; for patients with CCI <7, NLR <9 and in ACEI/ARBs therapy was of 0%.ConclusionsHigh comorbidity burden, high levels of NLR and the undertreatment with ACEI/ARBs were the main prognostic indicators of in-hospital mortality. The risk stratification of COVID-19 patients at hospital admission would help the clinicians to take care of the high-risk patients and reduce the mortality.

Clinical Characteristics and Factors Associated with Heart Failure Readmission at a Tertiary Hospital in North-Eastern Tanzania.

Introduction Heart failure (HF) is characterized by frequent episodes of decompensation, leading to a high hospitalization burden. More than 50% of index hospitalizations for HF patients return within 6 months of discharge. Once the patient is readmitted, the risk of further disease progression and the mortality rate are increased. A lot of patients are readmitted due to factors such as poor medication adherence, infections, or worsening comorbidities. The aim of our study was to identify the inpatient burden of HF readmission and to identify the factors associated with early readmission. Methods A hospital-based cross-sectional analytical study was conducted from November 2018 to April 2019 within the medical wards at Kilimanjaro Christian Medical Centre (KCMC), which is a teaching and referral hospital in north-eastern Tanzania. The study population included all patients with HF admitted within the medical ward. Data were collected using questionnaires and blood and radiological investigations, and analysis was done using Statistical Package for Social Science (SPSS) version 25. Chi-square test was used to compare proportions of categorical variables. Logistic regression was used to determine the likelihood for readmission, and p-value of <0.05 was considered to be statistically significant. Results A total of 353 patients were identified with HF, of whom 136 (38.5%) had a previous admission. Of the 136 patients analysed, the mean age was 62.8 years (SD 17.1), and 86 (63.2%) were females. Within 30 days after discharge, 34 (25.0%) of the patients were readmissions. Factors for early readmission were unemployment (OR = 2.38, 95% CI = 1.02–5.54, p = 0.043), poor medication adherence (OR = 3.87, 95% CI = 1.67–8.97, p = 0.002), absence of angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) (OR = 2.40, 95% CI = 1.09–5.31, p = 0.030), and pleural effusion (OR 3.25, 95% CI = 1.44–7.32, p = 0.004). Conclusion Heart failure is a burden due to a large number of admissions and readmissions. Factors such as poor medication adherence and absence of adequate HF therapy, especially the absence of regimes containing ACEI or ARB, need to be targeted to reduce the number of readmissions. This will help reduce the risk of further decompensations, disease progression, and mortality rate.

Systemic Angiopoietin-1/2 Dysregulation Following Cardiopulmonary Bypass in Adults

Aim:Vascular leakage following cardiopulmonary bypass contributes to morbidity. Angiopoietin-1 and -2 are biomarkers of endothelial dysfunction. Our aim was to characterize Ang-1 and -2 association with clinical characteristics and outcomes.Methods:Observational cohort study measuring Ang-1/-2 with a panel of cytokines in adults undergoing cardiopulmonary bypass.Results:Ang-2 levels increased immediately postop whereas Ang-1 levels decreased over time. No significant correlation was found with other inflammatory mediators. High correlation was found between the hospital length of stay and Ang-2 increase at 24 h (rho = 0.590; p < 0.0001). The predictors of Ang-2 increase were female gender, cross clamp time, transfusion of blood and absence of angiotensin-converting enzyme inhibitor as a pre-op medication.Conclusion:Angiopoietins can detect vascular leakage early and could impact patient's management to decrease length of stay after cardiac surgery.

A Polymorphism in the XPNPEP2 Gene Is Associated with the Development of Hypotensive Transfusion Reactions without ACE Inhibitors.

Abstract 3140Poster Board III-77 IntroductionHypotensive transfusion reactions (HTRs) have been associated with the transfusion of different blood products. They are characterized by the rapid onset and disappearance of hypotension upon starting and finishing the transfusion respectively. The use of ACE inhibitors has been associated with HTRs. However, there are reported HTRs in patients not taking ACE inhibitors. An inability to break down bradykinin (BK) generated during the infusion/transfusion is suggested to be responsible for the hypotensive effect. Angiotensin-converting enzyme (ACE) and aminopeptidase P (APP) are primarily responsible for degradation of BK. We hypothesize that the C-2399A single-nucleotide polymorphism in the membrane-bound APP gene XPNPEP2 (SNP rs3747343) may be linked to HTRs. This polymorphism is present upstream of the coding sequence of the APP gene and has already been associated with severe hypotension in an angioedema patient treated with an ACE inhibitor. This suggests that it may have an important regulatory role. Patients and MethodsWith the approval of our IRB, patients' samples were collected, de-identified, and then used for testing. Specimens from 4 patients who presented with classic HTRs while not taking ACE inhibitors were analyzed through sequencing of DNA acquired from pre-transfusion blood samples. The same primers were used for PCR and sequencing (5'-GAGTATTATGTGGGGACCATCC-3' and 5'-ATGCCTCGCAGAGACAAGAG-3'). Samples were sequenced in both sense and antisense directions. ResultsAmong these patients, two (50%) were found to possess the C-2399A mutation. One was found to have changes in both reference and complementary strands while the other had a C/A mutation only in one strand. ConclusionsThese results indicate that the C-2399A polymorphism may be a contributing factor in the development of HTRs and that it may promote HTRs in the absence of ACE inhibitors. The hypotensive effect may be due to a structural or regulatory change caused by C-2399A though it also seems that other factors may be involved since not all patients assayed possessed the mutation. Further screening of additional contributing factors responsible for HTRs is necessary to fully comprehend the pathogenesis of this type of transfusion reaction.Keywords: XPNPEP2, C-2399A, ACE Inhibitors, Hypotensive Transfusion Reactions, aminopeptidase P.Figure 1: Table of ResultsPatient1Age/SexTransfusion Product1ACE InhibitorsSequencing Result2Clinical Setting170/MSDPNoA,TPost CABG4279/FRBCNoC,TPost CABG370/FRBCNoC,GPost CABG417/FFFPNoC,GEndoscopic procedure1Randomly Assigned ID; 2 SDP = Single donor platelets; RBC = Red Blood Cells; FFP = Fresh Frozen Plasma; 3Normal result is C,G;4CABG = Coronary Artery Bypass Graft Surgery DisclosuresNo relevant conflicts of interest to declare.

Cardiovascular surgery in children with Marfan syndrome or Loeys-Dietz syndrome

This study was undertaken to assess the frequency and outcome of cardiovascular surgery in children with Marfan or Loeys-Dietz syndrome. A retrospective review from 2 regional Marfan subspecialty clinics was performed. Between 1997 and 2007, 204 children with Marfan syndrome and 17 children with Loeys-Dietz syndrome were followed serially. Of these patients, 35 were identified who had undergone cardiovascular surgery at 18 years of age or less. Demographic, echocardiographic, and surgical data were collected. Surgery was performed at a median of 3 years (0-15 years) after diagnosis and a mean age of 11.5 +/- 6.2 years. Aortic root replacement was the initial surgery in 30 patients, and mitral valve surgery was the initial surgery in 8 patients, with 3 patients undergoing both. Aortic root replacement was performed using a composite root replacement in 9 patients and valve-sparing techniques in 21 patients (remodeling in 8 patients and reimplantation in 13 patients). Eight patients underwent reoperation at a mean of 4.7 +/- 3.0 years after aortic surgery: 3 for aortic insufficiency, 2 for dissection, 2 for valve thrombosis, and 1 for a distal aneurysm. Adverse outcomes included reoperation in 8 patients, aneurysm in 1 patient, and death due to dissection or stroke in 3 patients. Variables associated with an adverse outcome included preoperative aortic insufficiency, valve replacement, and absence of angiotensin-converting enzyme inhibitor therapy. Patients with Marfan or Loeys-Dietz syndrome requiring surgery during childhood have a favorable long-term outcome. Those undergoing valve-sparing root replacement or mitral valve repair have a low risk for reoperation. Postoperative angiotensin-converting enzyme inhibitor therapy confers clinical benefit.

Blood Pressure in Children With Chronic Kidney Disease

To characterize the distribution of blood pressure (BP), prevalence, and risk factors for hypertension in pediatric chronic kidney disease, we conducted a cross-sectional analysis of baseline BPs in 432 children (mean age 11 years; 60% male; mean glomerular filtration rate 44 mL/min per 1.73 m(2)) enrolled in the Chronic Kidney Disease in Children cohort study. BPs were obtained using an aneroid sphygmomanometer. Glomerular filtration rate was measured by iohexol disappearance. Elevated BP was defined as BP >or=90th percentile for age, gender, and height. Hypertension was defined as BP >or=95th percentile or as self-reported hypertension plus current treatment with antihypertensive medications. For systolic BP, 14% were hypertensive and 11% were prehypertensive (BP 90th to 95th percentile); 68% of subjects with elevated systolic BP were taking antihypertensive medications. For diastolic BP, 14% were hypertensive and 9% were prehypertensive; 53% of subjects with elevated diastolic BP were taking antihypertensive medications. Fifty-four percent of subjects had either systolic or diastolic BP >or=95th percentile or a history of hypertension plus current antihypertensive use. Characteristics associated with elevated BP included black race, shorter duration of chronic kidney disease, absence of antihypertensive medication use, and elevated serum potassium. Among subjects receiving antihypertensive treatment, uncontrolled BP was associated with male sex, shorter chronic kidney disease duration, and absence of angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use. Thirty-seven percent of children with chronic kidney disease had either elevated systolic or diastolic BP, and 39% of these were not receiving antihypertensives, indicating that hypertension in pediatric chronic kidney disease may be frequently under- or even untreated. Treatment with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers may improve BP control in these patients.

Angiotensin receptor blockers in heart failure: meta-analysis of randomized controlled trials

ObjectivesWe sought to determine the effect of angiotensin receptor blockers (ARBs) on mortality and hospitalization in patients with heart failure (HF). BackgroundThere is uncertainty regarding the efficacy of ARBs as substitute or adjunctive therapy to angiotensin-converting enzyme inhibitors (ACEIs) in the treatment of HF. MethodsWe conducted a meta-analysis of all randomized controlled trials that compared ARBs with either placebo or ACEIs in patients with symptomatic HF. The pooled outcomes were all-cause mortality and hospitalization for HF. ResultsSeventeen trials involving 12,469 patients were included. Overall, ARBs were not superior to controls in the pooled rates of death (odds ratio: 0.96; 95% confidence interval: 0.75 to 1.23) or hospitalization (0.86; 0.69 to 1.06). Stratified analysis, however, showed a non-significant trend in benefit of ARBs over placebo in reducing mortality (0.68; 0.38 to 1.22) and hospitalization (0.67; 0.29 to 1.51) when given in the absence of background ACEI therapy. When compared directly with ACEIs, ARBs were not superior in reducing either mortality (1.09; 0.92 to 1.29) or hospitalization (0.95; 0.80 to 1.13). In contrast, the combination therapy of ARBs and ACEIs was superior to ACEIs alone in reducing hospitalization (0.74; 0.64 to 0.86) but not mortality (1.04; 0.91 to 1.20). ConclusionsThis meta-analysis cannot confirm that ARBs are superior in reducing all-cause mortality or HF hospitalization in patients with symptomatic HF, particularly when compared with ACEIs. However, the use of ARBs as monotherapy in the absence of ACEIs or as combination therapy with ACEIs appears promising.

Serum metabolism of bradykinin and des-Arg9-bradykinin in patients with angiotensin-converting enzyme inhibitor-associated angioedema

Angioedema (AE) associated with angiotensin-converting enzyme inhibitors (ACEi) is a rare, but potentially life-threatening adverse reaction. Several studies have suggested that bradykinin (BK) is responsible for ACEi-induced AE, but the mechanism remains unclear. We investigated the metabolism of BK and des-Arg9-BK in the serum of 20 patients with a history of ACEi-associated AE and 21 control (C) subjects. Synthetic BK was incubated with the sera for various periods of time and residual BK and generated des-Arg9-BK were quantified by specific and sensitive enzyme immunoassays. No significant difference of half-life (t1/2) of both BK and des-Arg9-BK could be measured between C subjects and patients with AE (AE) in absence of ACEi. However, an analysis according to the prolonged (+) or not (−) t1/2 of des-Arg9-BK allowed a new stratification of C subjects and AE patients in four subgroups. The preincubation of sera with enalaprilat at a concentration inhibiting ACE significantly prevented the rapid degradation of BK and des-Arg9-BK in these four subgroups. In presence of ACEi, a subgroup (50%) of AE patients (AE+) had a particularly significant rise of the t1/2 of des-Arg9-BK. Once ACE was inhibited, the concentration or the nature of the ACEi had no significant effect on the t1/2 of des-Arg9-BK. However, a test dilution of AE+ sera with a control (C) serum showed that an enzyme defect rather than a circulating inhibitor could be responsible for the abnormal metabolism of des-Arg9-BK when ACE is inhibited. In conclusion, half of the patients with ACEi-associated AE present in serum had an enzyme defect involved in the des-Arg9-BK metabolism leading to its accumulation. The B1 agonist could be responsible, at least in part, for the local inflammatory reaction associated with the AE.

Ventricular dilatation in the absence of ACE inhibitors: influence of haemodynamic and neurohormonal variables following myocardial infarction

ObjectiveTo examine the relation between patterns of ventricular remodelling and haemodynamic and neurohormonal variables, at rest and during symptom limited exercise, in the year following acute myocardial infarction in patients...

Role of Bradykinin in Anaphylactoid Reactions during Hemodialysis with AN69 Dialyzers

In vitro experiments have related anaphylactoid reactions in patients treated with angiotensin-converting enzyme (ACE) inhibitors during dialysis with AN69 membranes to excessive bradykinin generation using this negatively charged dialysis membrane. In the present clinical trial plasma bradykinin levels were followed during the early phase of dialysis in 10 patients, not being treated with ACE inhibitors, using AN69, cuprophane, and polysulfone membranes. Bradykinin was measured after extraction by radioimmunoassay. During this study one episode of anaphylaxis occurred during dialysis with the AN69 membrane. Blood samples were collected during the first 5 min of the adverse reaction and showed a more than 100-fold increase in the venous effluent of the AN69 dialyzer (baseline 40 +/- 3 vs. 4,900 +/- 130 fmol/ml after 5 min). Even though none of the patients received ACE inhibitors, there were 4 more asymptomatic individuals who displayed a more than two-fold increase in their plasma bradykinin concentrations in the venous effluent of the AN69 dialyzer. When these patients were treated either with cuprophane or with polysulfone dialyzers, no significant bradykinin formation was detected, nor were there any adverse events. Taken together, these findings show that anaphylactoid reactions with the AN69 membrane are due to excessive bradykinin generation which even may occur in the absence of ACE inhibitors.

Attenuation of myocardial reperfusion injury by sulfhydryl-containing angiotensin converting enzyme inhibitors.

Recent studies have suggested the beneficial effects of angiotensin converting enzyme (ACE) inhibitors against myocardial ischemic-reperfusion injury. This study was designed to compare the cardioprotective effects of two sulfhydryl ACE inhibitors, captopril and zofenopril, with those of a nonsulfhydryl ACE inhibitor, fosinopril. The efficacy of these ACE inhibitors to scavenge oxygen radicals in vitro were also examined. Isolated rat hearts perfused by the Langendorff technique were preperfused in the presence or absence of ACE inhibitors (50 microns for 15 minutes, and the hearts were then subjected to 30 minutes of ischemia followed by 30 minutes of reperfusion. Zofenopril and captopril, but not fosinopril, improved postischemic left ventricular functions and reduced myocardial cellular injury, as evidenced by improved recovery of the first derivative of left ventricular pressure development and reduced creatine kinase release compared with control (p less than .05). Coronary flow was significantly increased by captopril and zofenopril only. The same two drugs also inhibited the enhanced lipid peroxidation during reperfusion. Although significant differences were not noticed in the postischemic myocardial membrane phospholipid composition, captopril and zofenopril reduced nonesterified fatty acid contents, including palmitic, linoleic, oleic, and arachidonic acids. In vitro studies demonstrated that captopril and zofenopril were able to scavenge hydroxyl radicals. These results indicate that among three ACE inhibitors, two sulfhydryl-containing drugs, captopril and zofenopril, possess cardioprotective as well as free-radical scavenging abilities. Attenuation of phospholipid degradation and lipid peroxidation may be contributory to the protective effects observed in this study.