Receiving Angiotensin-converting Enzyme Inhibitors Research Articles

Effectiveness of a fixed combination of empagliflozin with metformin in reduction of cardiovascular risk in patients with uncontrolled arterial hypertension and decompensated type 2 diabetes mellitus

Objective is to study the effectiveness of a fixed combination of empagliflozin and metformin in reducing cardiovascular risk in patients with uncontrolled arterial hypertension (AH) and decompensated type 2 diabetes mellitus (DM). Materials and methods. 36 patients with uncontrolled AH and decompensated type 2 diabetes mellitus aged 45 to 60 were examined. Before inclusion in the study, all patients received standard antihypertensive (angiotensin‑converting enzyme (ACE) inhibitor or angiotensin‑II receptor blocker (ARB) in combination with a calcium channel blocker and a thiazide‑like diuretic), glucose‑lowering (metformin) and hypolipidemic (atorvastatin) therapy. However, target levels of blood pressure (BP), glycated haemoglobin (HbA1c) and lipids were not achieved. After the initial examination, all patients were prescribed a fixed combination of empagliflozin and metformin at a dose of 12.5 mg/1000 mg 1—2 times a day, and antihypertensive and hypolipidemic therapy was continued. Re‑examination was carried out after 20 weeks. In the work, a statistical analysis of the obtained data was carried out using standard methods using Microsoft Excel 7.0 and SPSS 19.0 application packages. Results. The transfer of the examined patients from previous ineffective hypoglycemic therapy to a fixed combination of empagliflozin with metformin against the background of standard antihypertensive and hypolipidemic therapy made it possible to achieve the target levels of HbA1c in 69% of patients and target BP levels in 64%. The frequency of reaching target BP levels in the subgroup of patients who received ARB was significantly higher than in the subgroup of patients who received ACE inhibitors. The specified therapy contributed to a significant reduction in body weight, reaching the target levels of low‑density lipoprotein cholesterol (LDL‑C) and non‑high‑density lipoprotein cholesterol (Non‑HDL‑C) in more than a third of patients, and reducing the severity of albuminuria in some patients. The tested therapy, in general, led to reduction in cardiovascular risk and did not cause side effects that could lead to discontinuation of treatment. Conclusions. The fixed combination of empagliflozin with metformin against the background of standard antihypertensive and hypolipidemic therapy in patients with uncontrolled hypertension and decompensated type 2 diabetes mellitus contributed to the achievement in the vast majority of patients of the target levels of HbA1c in the blood and BP levels, reduced body weight, positive changes in lipid metabolism and kidney function, and demonstrated the possibility of a significant reduction in cardiovascular risk. A more pronounced decrease in BP was detected in the case of a fixed combination of empagliflozin and metformin with ARB compared to ACE inhibitors in this category of patients.

Developmental aspects of metabolic syndrome in children under treatment with gastrointestinal lipase inhibitors

Alongside the increasing trends in obesity rates, there is a documented rise in the prevalence of metabolic syndrome (MetS) in children, dictating that each component of MetS should be identified as early as possible;and the treatment goal consists of reducing obesity, managing metabolic complications, insulin resistance, and also addressing hypertension (HTN).Aim of the study. To determine risk factors, the role of certain proinflammatory markers (TNF α, hs-CRP), and adipokines (leptin, adiponectin) in the onset of MetS in children and their evolution under treatment with gastrointestinal lipase inhibitors (GLI). Material and methods. The presented results were obtained as part of a project within the State Program 2020-2023 titled “Evolutionary Aspects of Metabolic Syndrome in Children Under Treatment with Gastrointestinal Lipase Inhibitors”, project number 20.80009.8007.33. The study included 57 children with MS (IDF, 2007). Depending on the pharmacological therapy associated with non-pharmacological treatment, the children in the research were divided into 3 groups: Group I- 23 children who received orlistat (orlip) - GLI, Group II - 15 children who received Angiotensin Converting Enzyme Inhibitors (ACEIs), and Group III - 19 children who received both GLI and ACEIs. The control group consisted of 50 normotensive and normal-weight children of similar age (gender ratio: 1:1). Risk factors, body mass index (BMI), waist circumference (WC), blood pressure values, total cholesterol (TC), LDL-C, HDL-C, triglycerides (TG), basal glycemia (BG), serum insulin, TNFα, hs-CRP, leptin, and adiponectin were analyzed initially and at the 3-month interval.The study protocol was approved by the Medical Ethics Committee of the Institute of Cardiology, Republic of Moldova (minutes no.2 dated February 20, 2020).Results: The majority of children in the study had a history of hereditary aggravated HTN and obesity, were sedentary or moderately sedentary, and had poor dietary habits. Among the components of MetS (IDF, 2007) associated with abdominal obesity, the following predominated: hypertension in 38 (66.7%) children, hypertriglyceridemia - 32 (56.1%%) children, increased basal blood glucose (BG) - 17(29.8%) children and hypo-HDL-C - 11 (19.3%) children. BMI at the 3-month interval from the initiation of medication decreased most significantly in group I (-4.025±1.267 kg/ m2), followed by group II (-3.33±0.972 kg/m2), and III (-3.046±0.840 kg/m2). WC decreased most notably in group III (-10.63±3.732 cm) compared to group II (-9.167±1.783 cm) and group I (-4.700±2.352 cm). Similar trends were observed for blood pressure values: group III (-18.75±1.897 mm Hg) vs group II (-12.167±1.359 mm Hg) vs group I (-3.900±4.613 mm Hg). LDL-C decreased essentially in group II (-0.46±0.211 mmol/l), while TG decreased in group III (-0.77±0.325 mmol/l) and II (-0.53±0.112 mmol/l). HDL-C increased by +0.60±0.274 mmol/l in group I, by +0.15±0.066 mmol/l in group II, and by +0.12±0.031 mmol/l in group III. Serum insulin decreased predominantly in group III (-9.36±4.53 µU/ mL). Similar trends were observed for BG (group III -1.24±0.322 mmol/l). TNF α decreased most significantly in group III (-2.65±0.911 pg/ml) compared to group I (-1.24±0.508 pg/ml) and group II (-1.61±1.018 pg/ml). hs-CRP decreased mainly in group I (-0.69±0.785 mg/l) and group II (-0.74±0.593 mg/l) compared to group III (-0.42±0.617 mg/l). Leptin values decreased significantly in all study groups at the 3-month interval from the initiation of medication (group I by-8.80±3.64 ng/ml, group II by -10.92±4.084 ng/ml, group III by -9.75±6.172 ng/ml). Adiponectin values increased by+1.83±1.087 µg/L in group III of the study.Conclusion: In combination with a calorie-restricted diet, regular physical exercise, and behavioral modifications, treatment with ILG and ACEIs in children with MetS in the study contributed to a decrease in the degree of obesity, blood pressure values, and normalization of the lipid and glucose profile, respectively. Additionally, it highlighted both the importance of prevention, early detection, and management of obesity, as well as the causal link between obesity, hypertension, and chronic inflammation.

Comparative estimation of the effects of antihypertensive medications on schizophrenia occurrence: a multinational observational cohort study

BackgroundThe association between antihypertensive medication and schizophrenia has received increasing attention; however, evidence of the impact of antihypertensive medication on subsequent schizophrenia based on large-scale observational studies is limited. We aimed to compare the schizophrenia risk in large claims-based US and Korea cohort of patients with hypertension using angiotensin-converting enzyme (ACE) inhibitors versus those using angiotensin receptor blockers (ARBs) or thiazide diuretics.MethodsAdults aged 18 years who were newly diagnosed with hypertension and received ACE inhibitors, ARBs, or thiazide diuretics as first-line antihypertensive medications were included. The study population was sub-grouped based on age (> 45 years). The comparison groups were matched using a large-scale propensity score (PS)-matching algorithm. The primary endpoint was incidence of schizophrenia.Results5,907,522; 2,923,423; and 1,971,549 patients used ACE inhibitors, ARBs, and thiazide diuretics, respectively. After PS matching, the risk of schizophrenia was not significantly different among the groups (ACE inhibitor vs. ARB: summary hazard ratio [HR] 1.15 [95% confidence interval, CI, 0.99–1.33]; ACE inhibitor vs. thiazide diuretics: summary HR 0.91 [95% CI, 0.78–1.07]). In the older subgroup, there was no significant difference between ACE inhibitors and thiazide diuretics (summary HR, 0.91 [95% CI, 0.71–1.16]). The risk for schizophrenia was significantly higher in the ACE inhibitor group than in the ARB group (summary HR, 1.23 [95% CI, 1.05–1.43]).ConclusionsThe risk of schizophrenia was not significantly different between the ACE inhibitor vs. ARB and ACE inhibitor vs. thiazide diuretic groups. Further investigations are needed to determine the risk of schizophrenia associated with antihypertensive drugs, especially in people aged > 45 years.

Is sarcopenia an associated factor of increased administration of specific medications in patients with heart failure? A systematic review and meta-analysis

BackgroundThere is controversy in relation to commonly used drugs in heart failure (HF) and their impact on muscle function. The aim of this study was to evaluate the odds of receiving specific medications often used in clinical practice by patients with HF and sarcopenia vs. without sarcopenia.MethodsA systematic literature search of cohort studies via databases (PubMed, Web of Science, Scopus, and Cochrane Library) was conducted from inception until March 2023. To determine if sarcopenia is linked to a higher number of specific HF-related medications, a meta-analysis using a random-effects model was used to calculate the pooled effects.ResultsOur main analyses showed no significant association of sarcopenia with administration of higher HF-related medication count vs. those without sarcopenia. Those with lower appendicular lean mass (ALM) had significantly lower odds of receiving angiotensin converting enzyme inhibitors (ACE-Is)/angiotensin receptor blockers (ARBs) (OR: 0.68, 95%CI 0.50–0.90, I2 = 12%, P < 0.01) vs. patients with higher ALM for which age could be an important confounder based on meta-regression. No statistically significant differences were found in relation to B-blockers OR: 0.84, 95%CI 0.63–1.12, I2 = 7%, P = 0.24) and loop diuretics (OR: 1.19, 95%CI 0.87–1.63, I2 = 0%, P = 0.27). Regarding handgrip strength, gait speed, and short physical performance battery, our narrative synthesis found mixed results.ConclusionThis systematic review and meta-analysis did not find a relationship of specific medication count in sarcopenia vs. without sarcopenia in patients with HF, although increased odds of ACE-I/ARB was shown in those with higher ALM.Systematic Review RegistrationPROSPERO (CRD42023411137).

Efficacy of the use of angiotensin converting enzyme inhibitors in the complex therapy of gastroduodenal erosions and ulcers in patients with unstable angina

Purpose of the study. To find out the effectiveness of the use of angiotensin-converting enzyme (ACE) inhibitors in the complex therapy of erosive and ulcer lesions of the stomach and duodenum in unstable angina pectoris (UA). Materials and methods. A survey of 109 patients with UA with gastroduodenal erosions and ulcers was carried out, taking into account their clinical signs, endoscopic features and the parameters of gastric secretion. The patients were divided into two groups depending on the nature of the treatment of erosions and ulcers. The first group included 40 patients treated with standard therapy, and the second one included 69 patients who additionally received ACE inhibitor lisinopril at an average dose of 7.27±0.16 mg a day. Results. The therapy by lisinopril resulted in decreasing of pain and dyspeptic syndrome, especially in patients with acute erosions, compared with conventional treatment group. According to endoscopic examination, in patients treated with lisinopril, an acceleration of repair processes in the tissues of the gastroduodenal zone was observed. The depth and size of damages, a reduction in the period of persistence of microbleeding signs and inflammatory changes in the periulcerous zone were also less pronounced in lisinopril patient’s group. In patients with acute erosions a decrease in the number and size of erosive defects of the mucous membrane was observed. The study of the parameters of gastric secretion showed that gastroduodenal erosions and ulcers in UA revealed the activation of the acid-peptic factor and a decreasing in the production of gastromucoproteins. Increased production of pepsinogen and a sharply reduced formation of protective mucus was observed in patients after conventional treatment, despite some positive dynamics. Normalization in pepsinogen secretion with some inhibition of the production of mucopolysaccharides was observed in Lisinopril treated patients at the end of therapy. Acid production in both groups was reduced, which was associated with could be provoked by an uptake of antisecretory agents. Conclusion. The use of ACE inhibitor lisinopril in the complex therapy in patients with UA with gastroduodenal erosions and ulcers is pathogenetically justified and clinically effective. This combination helps to reduce the duration of clinical signs, accelerate the healing of defects and normalize the parameters of gastric secretion.

THE PRESCRIBING TRENDS OF ACE-INHIBITORS AFTER MYOCARDIAL INFARCTION IN TERTIARY CARE HOSPITALS OF HAZARA REGION

Background: There is good evidence that angiotensin-converting enzyme (ACE) inhibitors are beneficial after myocardial infarction (MI). However, it is not known how widely this evidence is used in practice or whether all eligible patients receive this therapy. Objective: In three sizable tertiary care hospitals in the Hazara region, the study's objective was to evaluate the usage of ACE-inhibitors in patients who had experienced MI. Methods: Data collection from patients was used to collect the cases and examine the prescription pattern of use of ACE inhibitors, combination-based therapy, reasons for prescribing ACE inhibitors in STEMI, or reasons for prescribing ACE inhibitors in NSTEMI. To determine if proof-based prescribing of ACE-inhibitors following MI is taking place, data about ACE-inhibitor prescriptions is compared with recommended criteria. Descriptive statistics were used to estimate percentage frequencies. Results: There were 460 patients. 63.3% are male and 36.7% are female. 30% of patients who suffered an ST elevation MI received ACE inhibitors; in contrast, a greater part of patients (70%) who suffered a non-ST elevation MI received ACE inhibitors. 43.3% of the patients were prescribed ramipril, and 42% of the patients received lisinopril. Captopril, enalapril, quinapril, and fosinopril were prescribed to 7.4%, 5.4%, 1.5%, and 0.4% of patients, respectively. Ramipril was most commonly prescribed. It was also assessed that 44% of the patients received Β-blockers as combination therapy. The most prescribed Β-blocker was bisoprolol and then metoprolol. Conclusion: Most patients admitted to three tertiary care hospitals with myocardial infarction (MI) were prescribed an ACE inhibitor in an appropriate manner.

Clinical benefits of angiotensin receptor-Neprilysin inhibitor in adults with congenital heart disease

BackgroundThere are limited data about the clinical benefits of angiotensin receptor-neprilysin inhibitor (ARNI) in adults with congenital heart disease (CHD). The purpose of the study was to assess the clinical benefits (chamber function and heart failure indices) of ARNI in adults with CHD. MethodIn this retrospective cohort study, we compared the temporal change in chamber function and heart failure indices between 35 patients that received ARNI for >6 months, and a propensity matched control group (n = 70) of patients that received angiotensin converting enzyme inhibitor or angiotensin-II receptor blocker (ACEI/ARB) within the same period. ResultsOf the 35 patients in the ARNI group, 21 (60%) had systemic left ventricle (LV) while 14 (40%) had systemic right ventricle (RV). Compared to the ACEI/ARB group, the ARNI group had greater relative improvement in LV global longitudinal strain (GLS) (28% versus 11% increase from baseline, p < 0.001) and RV-GLS (11% versus 4% increase from baseline, p < 0.001), and greater relative improvement in New York Heart Association functional class (−14 versus −2% change from baseline, p = 0.006) and N-terminal pro-brain natriuretic peptide levels (−29% versus −13% change from baseline, p < 0.001). These results were consistent across different systemic ventricular morphologies. ConclusionsARNI was associated with improvement in biventricular systolic function, functional status, and neurohormonal activation, suggesting prognostic benefit. These results provide a foundation for a randomized clinical trial to empirically test the prognostic benefits of ARNI in adults with CHD, as the next step towards evidence-based recommendations for heart failure management in this population.

Renal function in patients with chronic kidney disease and hypertension degree 1–2 against the background of SARS-CoV-2

Renal function in patients with chronic kidney disease and hypertension degree 1–2 against the background of SARS-CoV-2

Polymorbidity and Polypragmasia in High and Very High Cardiovascular Risk Patients

Aim. Assessment of the level and structure of polymorbidity, features of pharmacotherapy therapy in patients of different age groups, belonging to the category of high and extremely high cardiovascular risk, observed in outpatient clinics.Material and methods. The single-stage study included 282 patients of high and very high cardiovascular risk who were divided into three groups: (1) age 45-59 years, (2) 60-74 years, (3) ≥75 years. The structure of polymorbidity and features of pharmacotherapy in different age groups patients were evaluated. The frequency of polypragmasia was determined, and treatment adequacy in patients over 65 years of age was analyzed using the STOPP / START criteria and the Beers criteria of 2019.Results. High and very high cardiovascular risk patients have been found to be highly polymorbid, polimorbidity level increasing with age. Thus, among elderly patients, ischemic heart disease, chronic heart failure (CHF) were more often detected, as well as a high frequency of concomitant and background conditions, especially bone and joint system involvement (osteoarthritis, rheumatoid arthritis). Polypragmasia (administration of ≥5 drugs) was detected in 150 patients (53.2%) and was more common among elderly patients. According to Beers criteria, there were 48 cases of inadequate medication prescribing in 46 (28.0%) elderly patients. According to 80 STOPP criteria, 75 cases of prescribing potentially non-recommended drugs to 55 patients (32.1%) were detected. According to 34 START criteria, 116 cases of non-prescribing of necessary drugs to 52 (30.4%) elderly patients were found. When assessing the frequency of prognosis modifying medication prescribing, patients with CHF in 107 (63.0%) cases received angiotensin converting enzyme inhibitors, and in 42 cases (24.5%) angiotensin II receptor antagonists had been prescribed. Thus, 87.5% CHF patients were receiving renin-angiotensin-aldosterone system blockers. Statins were administered in 225 (79.8%) cases, antiplatelet agents were pre-scribed in 157 (67.9%) cases, and 23 persons (9.9%) were on oral anticoagulants for atrial fibrillation.Conclusion. In the structure of the studied cohort most of the high and very high cardiovascular risk outpatients were polimorbid, elderly and senile. Polypragmasia has been detected in more than half of elderly outpatients (53%), irrational medication was found in 28% to 30% elderly patients. Most patients with CHF were on statins, antithrombotic therapy, and renin-angiotensin-aldosterone system blockers.

Cardiovascular ACE2 receptor expression in patients undergoing heart transplantation.

AimsMembrane‐bound angiotensin‐converting enzyme (ACE)2 is the main cellular access point for SARS‐CoV‐2, but its expression and the effect of ACE inhibition have not been assessed quantitatively in patients with heart failure. The aim of this study was to characterize membrane‐bound ACE2 expression in the myocardium and myocardial vasculature in patients undergoing heart transplantation and to assess the effect of pharmacological ACE inhibition.Methods and resultsLeft ventricular (LV) tissue was obtained from 36 explanted human hearts from patients undergoing heart transplantation. Immunohistochemical staining with antibodies directed against ACE2 co‐registered with cardiac troponin T (cTnT) and α‐smooth muscle cell actin (SMA) was performed across the entire cohort. ACE2 receptor expression was quantitatively assessed throughout the myocardium and vasculature. ACE2 was consistently expressed throughout the LV myocardium (28.3% ± 22.2% of cardiomyocytes). ACE2 expression was also detected in small calibre blood vessels (range, 2–9 μm), albeit at quantitatively much lower levels (5% ± 9% of blood vessels). There was no significant difference in ACE2 expression between patients receiving ACE inhibitors prior to transplantation and ACE inhibitor‐negative controls (P > 0.05). ACE2 expression did not differ significantly between the different diagnostic groups as the underlying reason for heart transplantation (ANOVA > 0.05). N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) (R 2 = 0.37, P = 0.0006) and pulmonary capillary wedge pressure (PCWP) (R 2 = 0.13, P = 0.043) assessed by right heart catheterization were significantly correlated with greater ACE2 expression in cardiomyocytes.ConclusionsThese data provide a comprehensive characterization of membrane‐bound cardiac ACE2 expression in patients with heart failure with no demonstrable effect exerted by ACE inhibitors.

Diagnosis and treatment in children with Nutcracker Syndrome: Single-center experience

Objective: It has been aimed to report the experience of our center regarding diagnosis and treatment experience in children with Nutcracker syndrome (NCS). Materials and Methods: The medical records of the seven patients who have admitted to the Department of Pediatric Nephrology of our hospital between February 2017 and March 2020 were evaluated retrospectively. The diagnosis of NCS was confirmed with renal Doppler ultrasound (RDUS) and magnetic resonance angiography (MRA) in these patients who have admitted with the complaints of hematuria and proteinuria. The patient data such as clinical characteristics, radiological findings, radiological signs and information about the applied medical treatment at baseline and the last control examination were recorded. Results: The mean levels of 24-h urine protein excretion in all the patients at baseline and the last control examination were 15,25±9,19 mg/m2/h and 9,8±3,94 mg/m2/h, respectively. The mean levels of 24-h urine protein excretion in the patients treated with ACE (angiotensin converting enzyme) inhibitor at baseline and the last control examination were 20±11,53 mg/m2/h and 9,6±6,44 mg/m2/h, respectively. (p=0,073). The mean levels of 24-h urine protein excretion were 11.7±6.39 mg/m2/h and 9.95±1.84 mg/m2/h in the patients not receiving ACE inhibitor treatment, at baseline and the last control examination respectively (p= 0,61). The mean angle value of the left renal vein in the aortomesenteric distance measured by RDUS examination performed in the upright position was 14,71±4,46 degrees. The anteroposterior diameter of the left renal vein (hilar/aortomesenteric) measured in the upright position was 6,4. Conclusion: The benign nature of NCS in young patients requires maintaining conservative approach.

THE EFFECT OF RAMIPRIL ON THE ALDOSTERONE/RENIN RATIO AND THE ALDOSTERONE/ANGIOTENSIN II RATIO IN PATIENTS WITH PRIMARY ALDOSTERONISM

Objective: The aldosterone/renin ratio (ARR) is recommended for case detection of PA. However, many anti-hypertensive medications [such as angiotensin-converting enzyme (ACE) inhibitors] and physiological factors have been reported to affect renin and aldosterone, thereby causing false-negative ARR screening results. We sought to investigate the diagnostic performance of the ARR and aldosterone/AngII ratio (AA2R) among PA patients receiving ramipril treatment. Design and method: Blood samples from 60 PA and 40 non-PA patients were collected, aiming to predict optimal PA screening cut-offs for the ARR and AA2R (using ROC analysis). Another 26 PA patients were recruited and were administered ramipril (5 mg tablet, once daily) for 2 weeks. Blood was collected in the morning of day 0 (basal), day 14 (2 h after taking ramipril) and day 15 (26 h after last dose ramipril). Plasma aldosterone (PAC), equilibrium AngI and AngII (eqAngI and eqAngII) were measured by LC-MS/MS, while renin concentration (DRC) and activity (PRA) were measured by immunoassays. Results: When PAC was measured by LC-MS/MS, the predicted PA screening cut-offs for the ARR_DRC, ARR_PRA and AA2R were 53.9 (pmol/mU), 495.9 (pmol/L)/(ng/ml/h) and 8.3 (pmol/pmol), respectively. Compared to the basal levels, eqAngII and ACE activity (ACE-S, eqAngII/eqAngI) both decreased (P &lt; 0.01) after ramipril treatment, whereas DRC, PRA and eqAngI all increased (P &lt; 0.01 or P &lt; 0.05). Although median PAC tended to fall from 504.9 (day 0) to 458.3 (day 14) and to 488.0 (day 15) pmol/L, the changes were not statistically significant. On day 14, five patients displayed false-negative results in both ARR_DRC and ARR_PRA, whereas no false-negative AA2R result was observed. On day 15, three patients still demonstrated false-negative screening results, including one with both false-negative ARR_DRC and ARR_PRA, one with both false-negative ARR_DRC and AA2R, and one with false-negative ARR_PRA only. Conclusions: Although PAC did not change significantly, the changes of renin, eqAngI, eqAngII and ACE-S were consistent with ramipril's effect on ACE. Unlike the ARR which can be affected by ACE inhibitors causing false-negative screening results, the AA2R seems to be superior in PA screening among subjects who are receiving ACE inhibitors.

Profile of Pediatric Rheumatic Heart Disease Patients with Mitral Regurgitation Receiving Angiotensin-Converting Enzyme Inhibitor in dr. Saiful Anwar General Hospital Malang

Background : ACE inhibitors through reverse remodeling mechanisms may encounter secondary LV changes due to rheumatic MR. Studies regarding RHD in Indonesia, however, remain limited. Objectives : This study purposed to define the characteristic profile of pediatric rheumatic heart disease patients with mitral regurgitation who received ACE inhibitors. Methods : This descriptive observational study involved 47 pediatric RHD patients in the Pediatric Cardiology Outpatient Department of dr. Saiful Anwar General Hospital from November 2018 to June 2019. Patients were divided into the captopril group and the no captopril group. The Captopril group was defined as patients who had been receiving captopril for more than or equal to 12 months prior to the study. Data about demographic and echocardiographic parameters were analyzed. Results: Female patients were predominant (68%), with a mean age of 12.1 years and body mass index (BMI) of 17.2 kg/m2. The Captopril group revealed younger age, higher BMI, and longer initial time of RHD diagnosis compared to the no captopril group. Evaluation of LV remodeling parameters demonstrated that the captopril group had smaller LVIDd, lower LVMI, higher FS, and higher LVEF. LVPWd dan RWT were found to be relatively similar among both groups. Evaluation of MR grade revealed that the captopril group showed the lower value of MR VC, MR EROA, and MR regurgitant volume, as well. Conclusion: Pediatric rheumatic MR receiving ACE inhibitors revealed smaller LVIDd, lower LVMI, lower MR grade, higher FS, and higher LVEF compared to patients receiving no ACE inhibitors.

Antihypertensive Prescribing for Uncomplicated, Incident Hypertension: Opportunities for Cost Savings

BackgroundA range of first-line similarly effective medications ranging in price are recommended for treating uncomplicated hypertension. Considering drug costs alone, thiazides and thiazide-like diuretics are the most cost-efficient option. We determined incident prescribing of thiazides for newly diagnosed hypertension as first-line treatment in Alberta, factors that predicted receiving thiazides vs more costly medications, and how much could be saved if more patients were prescribed thiazides. MethodsUsing a retrospective cohort design, factors predicting receiving thiazides vs other agents were determined using mixed effects logistic regression. Cost savings were simulated by shifting patients from other antihypertensive medications to thiazides and calculating the difference. ResultsWithin our cohort of 89,548 adults, only 12% received thiazides as first-line treatment whereas 44% received angiotensin converting enzyme inhibitors, 17% received angiotensin receptor blockers, 16% received calcium channel blockers, and 10% received β-blockers. Antihypertensive medications were typically prescribed by office-based, general practitioners (88%). Being male and receiving a prescription from a physician with ≥ 20 years of practice and a high clinical workload were associated with increased odds of receiving nonthiazides. In the extreme case that all patients received thiazides as their first prescription, spending would have been reduced by a maximum of 95% (CAD$1.8 million). ConclusionsOnly 12% of Albertan adults with incident, uncomplicated hypertension were prescribed thiazides as first-line treatment. With the opportunity for drug cost savings, future research should evaluate the risk of adverse events and side effects across the drug classes and whether the costs associated with managing those risks could offset the savings achieved through increased thiazide use.

Impact of acute kidney injury in patients prescribed angiotensin-converting enzyme inhibitors over the first two years of life.

The association of long-term acute kidney injury (AKI) risk with angiotensin-converting enzyme (ACE) inhibitor use in neonates/infants is poorly understood. We examined this association to identify potential AKI risk factors. We retrospectively evaluated 119 children aged < 2years (72 boys; median age, 5.0months) who received ACE inhibitors for congenital heart disease for ≥ 6months between January 2009 and June 2019. We monitored the occurrence of AKI, defined according to the Kidney Disease Improving Global Outcomes guidelines. Demographic and clinical data were extracted from medical records. Risk factors associated with AKI onset were identified by a Cox proportional hazards regression analysis of variables previously identified as risk factors of AKI and those significant in a univariate analysis. Thirty-three of 119 patients (28%) developed AKI at a median follow-up of 1.3years (interquartile range, 0.8-3.2years). AKI incidence was 1257 events per 10,000 patient-years. Concomitant tolvaptan use (hazard ratio [HR], 3.81; 95% confidence interval [CI], 1.82-7.97; P < 0.01) and Down syndrome (HR, 3.22; 95% CI, 1.43-7.29; P < 0.01) were identified as independent risk factors of AKI onset. AKI was strongly associated with concomitant tolvaptan use and Down syndrome in our study population. Physicians should consider these factors when prescribing ACE inhibitors for neonates/infants. Low-dose ACE inhibitors slow CKD progression because of their antifibrotic properties. ACE inhibitors may be beneficial for patients with Down syndrome who have underlying CKD in a non-acute setting. Therefore, they should be administered to such patients with caution.

Effect of angiotensin receptor blockers and angiotensin converting enzyme 2 on plasma equilibrium angiotensin peptide concentrations in dogs with heart disease.

BackgroundThe pathophysiology of heart failure involves maladaptive angiotensin peptides (APs) and enzymes, including angiotensin 2 (AT2) and angiotensin converting enzyme (ACE), as well as recently described alternative components, such as angiotensin 1‐7 (Ang1‐7) and angiotensin converting enzyme 2 (ACE2). The relative effects of different neurohormonal‐targeting drugs on balance of APs in dogs with heart disease are unknown.Hypothesis/ObjectivesPlasma AP concentrations differ in dogs receiving angiotensin converting enzyme inhibitors (ACEIs) vs angiotensin receptor blockers (ARBs) and recombinant human ACE2 (rhACE2) will further increase these differences.AnimalsEight dogs with degenerative mitral valve disease (DMVD).MethodsProspective open‐label trial. Equilibrium concentrations of APs from plasma during PO ACEI treatment and then after 14 days of PO ARB treatment using telmisartan were measured using liquid chromatography‐tandem mass spectroscopy before and after in vitro incubation with rhACE2.ResultsConcentration of Ang1‐7 was increased during ARB treatment (Ang1‐7: 443 pg/mL; 95% confidence interval [CI] = 247‐794 pg/mL) vs ACEI (Ang1‐7: 182 pg/mL; 95% CI = 66.2‐503 pg/mL; P = .01). Incubation with rhACE2 decreased traditional APs while increasing beneficial alternative APs, and Ang1‐7 was significantly higher in the ARB + rhACE2 (880 pg/mL; 95% CI = 560‐1383 pg/mL) vs ACEI + rhACE2 (455 pg/mL; 95% CI = 188‐1104 pg/mL; P = .03) group. The most favorable theoretical AP profile was achieved in the ARB + rhACE2 group.Conclusions and Clinical ImportanceThe AP profile during telmisartan treatment is associated with higher plasma Ang1‐7 as compared with during ACEI. This favorable shift is potentiated in vitro by combination of ARB + rhACE2. These data support potential AP‐targeting strategies and drugs in dogs with DMVD.

Influence of different anti‐hypertensive drugs on gingival overgrowth: A cross‐sectional study in a Turkish population

The purpose of this study was to evaluate the occurrence rate of drug-induced gingival overgrowth (DIGO) in patients treated with angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and calcium channel blockers (CCBs) such as amlodipine, lercanidipine, and benidipine, as well as to assess the relationship of those mentioned above with medication variables and oral hygiene. Sociodemographic details, DIGO, and clinical periodontal parameters were obtained from one hundred and thirty-one patients receiving ACE inhibitors, ARBs, and CCBs for a period of at least 2years. The occurrence rate of DIGO was 19.6% in patients using CCB, 12.5% in the ARB group, and 7.5% in the ACE inhibitor group. In a subgroup analysis of CCBs, DIGO was found to be 31.8% in the amlodipine group, 13.3% in the lercanidipine group, and 7.1% in the benidipine group. While there was a significant relationship between amlodipine drug dosage and DIGO, no association was found between the duration of therapy and DIGO in all CCB subgroups. There was no difference between the groups in terms of DIGO. Duration of therapy and drug dosage did not affect the severity of DIGO in both ACE inhibitors and ARB groups.

Effects of Ramipril on the Aldosterone/Renin Ratio and the Aldosterone/Angiotensin II Ratio in Patients With Primary Aldosteronism.

The aldosterone/renin ratio (ARR) is currently considered the most reliable approach for case detection of primary aldosteronism (PA). ACE (Angiotensin-converting enzyme) inhibitors are known to raise renin and lower aldosterone levels, thereby causing false-negative ARR results. Because ACE inhibitors lower angiotensin II levels, we hypothesized that the aldosterone/equilibrium angiotensin II (eqAngII) ratio (AA2R) would remain elevated in PA. Receiver operating characteristic curve analysis involving 60 patients with PA and 40 patients without PA revealed that the AA2R was not inferior to the ARR in screening for PA. When using liquid chromatography-tandem mass spectrometry to measure plasma aldosterone concentration, the predicted optimal AA2R cutoff for PA screening was 8.3 (pmol/L)/(pmol/L). We then compared the diagnostic performance of the AA2R with the ARR among 25 patients with PA administered ramipril (5 mg/day) for 2 weeks. Compared with basally, plasma levels of equilibrium angiotensin I (eqAngI) and direct renin concentration increased significantly (P<0.01 or P<0.05) after ramipril treatment, whereas eqAngII and ACE activity (eqAngII/eqAngI) decreased significantly (P<0.01). The changes of plasma renin activity and plasma aldosterone concentration in the current study were not significant. On day 14, 4 patients displayed false-negative results using ARR_direct renin concentration (plasma aldosterone concentration/direct renin concentration), 3 of whom also showed false-negative ARR_plasma renin activity (plasma aldosterone concentration/plasma renin activity). On day 15, 2 patients still demonstrated false-negative ARR_plasma renin activity, one of whom also showed a false-negative ARR_direct renin concentration. No false-negative AA2R results were observed on either day 14 or 15. In conclusion, compared with ARR which can be affected by ACE inhibitors causing false-negative screening results, the AA2R seems to be superior in detecting PA among subjects receiving ACE inhibitors.

Phenotypic spectrum and antialbuminuric response to angiotensin converting enzyme inhibitor and angiotensin receptor blocker therapy in pediatric Dent disease.

BackgroundTo characterize the phenotypic spectrum and assess the antialbuminuric response to angiotensin converting enzyme (ACE) inhibitor and/or angiotensin receptor blocker (ARB) therapy in a cohort of children with Dent disease.MethodsThe patients’ clinical findings, renal biopsy results, genetic and follow‐up data were analyzed retrospectively. Mutations in CLCN5 or OCRL were detected by next‐generation sequencing or Sanger sequencing.ResultsOf 31 Dent disease boys, 24 carried CLCN5 and 7 carried OCRL mutations. Low molecular weight proteinuria and albuminuria were detected in all cases. Nephrotic‐range proteinuria and severe albuminuria were identified in 52% and 62% of cases, respectively; by 7 years of age, 6 patients had hematuria and nephrotic‐range proteinuria, and 7 patients had hematuria and moderate to severe albuminuria. In addition to disease‐related renal features, patients with Dent‐1 disease also presented with congenital cataract (1/9) and developmental delay (2/7). Seventeen of 31 patients underwent renal biopsy. Glomerular changes included mild glomerular lesions, mesangial proliferative glomerulonephritis and focal segmental glomerular sclerosis. Thirteen of the 31 patients had follow‐up records and received ACE inhibitor and/or ARB treatment for more than 3 months. After a median 1.7 (range 0.3–8.5) years of treatment, a reduction in the urinary microalbumin‐to‐creatinine ratio was observed in 54% of children.ConclusionsHematuria with nephrotic‐range proteinuria or moderate to severe albuminuria was common in Dent disease patients. Extrarenal manifestations were observed in Dent‐1 patients, which extends the phenotypic spectrum. In addition, ACE inhibitors and ARBs are well tolerated, and they are partially effective in controlling albuminuria.

P1010EFFECTS OF SGLT2 INHIBITORS ON DIABETIC NEPHROPATHY: PODOCYTURIA ON FOCUS

Abstract Background and Aims Sodium-glucose co-transporter 2 (SGLT2) inhibitors which are a class of oral anti-diabetic drugs are being used in the treatment of type 2 diabetes (T2D). Basically these drugs reduce blood glucose by blocking glucose reabsorption of primary sodium-coupled glucose transporter in the proximal tubules. Diabetic nephropathy (DN) is a progressive disease with the pathology of glomerular filtration barrier damage and loss of podocytes. In this respect, podocyturia which is the case characterized with presence of podocytes in urine have recently been considered to be a candidate marker for glomerular damage. Therefore, we aimed to investigate effects of SGLT2 inhibitors on glomerulus through the evaluation of podocyturia in DN patients. Method Our study population was composed of two T2D patient groups; one of which received SGLT2 inhibitor (SGLT2 group) and the other one is control which did not received. Patients with T2D for at least 5 years, diagnosed with DN and having microalbuminuria &amp;gt;30 mg/day, glomerular filtration rate (GFR) &amp;gt;60 ml/min and HbA1c&amp;lt; 8.5 were involved. In addition, all patients had received angiotensin converting enzyme inhibitor or angiotension receptor blocker for at least 6 months. Nephrologic parameters of patients were monitored before and 3rd and 6th month of follow up period. Patients’ age, sex, diabetes duration and HbA1c value were obtained from medical charts. GFR was calculated using the abbreviated MDRD formula. Microalbuminuria was measured in 24 hour urine. Number of podocytes in the urine was determined by immunocytochemical staining of two different markers as podocalyxin (podx) and synaptopodin (synp). Statistical analyses were carried out using Statistical Package for the Social Sciences version (SPSS) 24.0 and statistical significance was set as p&amp;lt;0.05. Results We evaluated a total of 29 patients (mean age: 57.59 ± 9.66). The number of patients for SGLT2 and control groups are 18 (mean age: 54.89 ± 7.73) and 11 (mean age: 62.00 ± 11.60) respectively. Between these two groups, there was no statistical difference with respect to durations of diabetes (p=0.875) and HbA1c (p=0.05) values except for age (p=0.023) in which control group is statistically higher than the SGLT receiving group. Among the patients receiving SGLT2 inhibitor, podocyturia and microalbuminuria (mca) levels in the 6th month of follow up period were statistically lower than the initial ones [p=0.039 (synp), p=0.016 (podx) and p=0.011 (mca) respectively] while there was no statistical difference for creatinine clearance rate between the initial and follow up period (p:0.371 and ;p=0.111) (Figure-1). For control group, although podocyturia was significantly reduced in the 6th month of follow up period [p=0.013 (synp) and p:0.005 (podx)], microalbuminuria (p=0.263) in addition to creatinine clearance (p:0.214; p=0.173) did not change significantly (p=0.263). Furthermore, while there was no significant difference for initial microalbuminuria level between the control and SGLT2 groups (p=0.353); in the 3rd and 6th month follow up period, microalbuminuria was significantly lower than the control group accordingly (p=0.011 and p=0.015 respectively). Conclusion According to our preliminary results; patients receiving SGLT2 inhibitors had better microalbuminuria levels than the ones did not and this parameter was correlated with podocyturia. However, even though microalbuminuria of the control group did not change during the follow up period, podocyturia was found out as reduced in the 6th month of follow up period. This discrepancy in the podocyturia level could be resulted from lower number of patients in control so that there is need for evaluation of more patients to emphasize podocyte protective effect of SGLT2 inhibitors.