Use Of Angiotensin-converting Enzyme Inhibitors Research Articles

Abstract 4131412: Effects of Angiotensin Converting Enzyme Inhibition And Afterload Reduction in Single Ventricle Patients Prior To Fontan: Not What You Might Think

Introduction: Pts with single ventricle (SV) after bidirectional Glenn (BDG) are placed on angiotensin converting enzyme inhibitors (ACEI) to reduce afterload, improve ventricular performance and allow for decreased systemic to pulmonary collateral flow (APC). No large scale data exists to support ACEI use in BDG pts to accomplish this. We hypothesized that ACEI may not perform as predicted. Goals: To determine if ACEI use in BDG pts decreases APC and improves ventricular function. Methods: Single center retrospective study of all BDG pts who underwent cardiac magnetic resonance (CMR) from 2010 to present. Demographics, medication, ventricular function and flow data were collected. Pts included were >1 year old and on ACEI for >3 months prior to CMR. Wilcoxon and Fisher Exact tests were used. Significance P<0.05 Results: Of the 320 BDG pts (median 2.8 years old) studied, 137 (43%) were treated with ACEI. See table for all data. There was no difference in age, sex, medications (except for ACEI) or body surface area (BSA) between both groups. APC as a % of aortic flow and APC/BSA were not different between those treated with ACEI compared to those who were not, whether right (RV) or left ventricle (LV) dominant. There was no correlation of APC with time on ACEI or ACEI dosage. Ejection fraction (EF) was lower and end-diastolic volume (EDV) was higher in BDG on ACEI for the entire group and RVs. Although LV EDV was higher with those on ACEI, LV EF was the same for those on ACEI and those who weren’t (graph). APC as a % of aortic flow and APC/BSA positively correlated with EDV (rho 0.25-0.34, P<.001). There was no difference in atrioventricular valve regurgitation between those on ACEI and those who were not (median 5 vs 6% respectively). As a surrogate for cerebral blood flow (CBF), superior vena caval (SVC) flow was lower for those on ACEI compared to those who were not. Conclusion: BDG pts treated with ACEI did not demonstrate decreased APC or improved ventricular performance. There is a suggestion that ventricular performance may be worse on ACEI. CBF is decreased in BDG on ACEI using SVC flow as a surrogate. This suggests that ACEI use in SV pts at the BDG stage is not indicated and should be discouraged.

Calcium Channel Blocker Versus Renin-Angiotensin System Inhibitor in Risk of Kidney Cancer Among Patients With Hypertension: A Propensity Score-Matched Cohort Study.

Use of antihypertensive medications could be associated with an increased risk of kidney cancer. Despite their various mechanisms of action, whether this association differs between different classes of medications remains unclear. The objective of this study is to compare the risk of kidney cancer between first-line treatment options of antihypertensive medications in a hypertensive population. In this retrospective cohort study, we used the MarketScan Databases (2007-2021). We included individuals older than 30 years of age with a diagnosis of hypertension who received first-line medications for hypertension, which included three classes: angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), and dihydropyridine calcium channel blockers (dCCB). We applied a propensity score matching method and created three separate cohorts: (1) ARB versus ACEI, (2) dCCB versus ACEI, and (3) dCCB versus ACEI. For non-dCCB, we repeated the analyses. The primary outcome was kidney cancer incidence. To assess kidney cancer risk, we applied multivariable conditional Cox proportional hazards models. In the first cohort, ARB use was associated with an increased risk of kidney cancer compared to ACEI use (hazard ratio [HR] 1.10, 95% confidence interval [CI] 1.02-1.18). In the second cohort, dCCB use was associated with an increased risk of kidney cancer compared to ACEI use (HR 1.29, 95% CI 1.18-1.40). In the third cohort, dCCB use was associated with a higher risk of kidney cancer compared to ARB use (HR 1.17, 95% CI 1.08-1.28). Null association was shown when comparing non-dCCB with ACEI or ARB use. Use of dCCB showed a higher risk of kidney cancer compared to ACEI or ARB use in patients with hypertension.

Heterologous Versus Homologous COVID-19 Boosters: Immune Response Outcomes in Renal Transplant Recipients.

We aimed to investigate the immune responses to homologous and heterologous COVID-19 booster vaccinations in renal transplant recipients (RTRs) and to identify factors affecting these responses. In this prospective multicenter observational study, we measured the antibody kinetics of 90 RTRs using the chemiluminescent microparticle immunoassay method. The mean age of participants was 45.2 ± 11.4 years, with 35.6% being female. On the 42nd day after the first vaccine dose, the median antibody level was 16.7 (IQR 2.5-249.5) AU/mL, and the seropositivity rate was 60% (n = 36). Mycophenolic acid (MFA) (OR: 0.087, 95% CI: 0.024-0.311) and ACE inhibitor use (OR: 0.203, 95% CI: 0.052-0.794) were identified as independent factors affecting seropositivity. Patients who received the Pfizer/BioNTech booster had significantly higher antibody levels compared to those who received the CoronaVac/Sinovac booster (p = 0.021). Additionally, a significantly higher rate of COVID-19 positivity was observed among patients who received the CoronaVac/Sinovac booster (p = 0.031). Heterologous COVID-19 booster vaccination is significantly more effective than homologous inactivated booster vaccination in enhancing immune responses and preventing new infections in RTRs. MFA and ACE inhibitor usage were independent factors affecting seropositivity. Additional COVID-19 vaccine doses are needed in this patient group.

5-year valve academic research consortium-3 outcomes and predictors of mortality in a 10-year Asian transcatheter aortic valve implantation registry

Abstract Background Transaortic valvular implantation (TAVI) has revolutionised the management of aortic stenosis (AS). Uptake in Asia has caught up in recent years, after an initial lag due to expensive cost, limited subsidies, and scarce accessibility. Hence, longitudinal outcomes of TAVI remain largely unknown in Asian patients. Purpose This study aims to present the 5-year mortality endpoints in an Asian cohort followed up over a decade. Methods 253 patients with symptomatic severe aortic stenosis status post TAVI were retrospectively enrolled at a tertiary academic hospital from 2010-2021. The main outcomes were defined as short-term (30-day), mid-term (1-year) and long-term (5-year) all-cause mortality. Baseline demographics, procedural findings and clinical outcomes were analysed. Kaplan-Meier curves and multiple Cox regression analyses were constructed. Results The mean age was 75.2 + 10.2 years. 120 (47.4%) patients were female and 167 (66%) were Chinese. 168 patients (66.7%) received balloon-expandable valves, 80 patients (31.7%) underwent self-expandable valves, and 4 patients (1.6%) had mechanical-expandable valves. Malignancy was associated with worse short-term mortality at 30-days (HR 3.65, p = 0.054), while pulmonary disease and previous stroke were associated with worse long-term mortality at 5-years (HR 2.27, p = 0.012 and HR 2.02, p = 0.064). Worse all-cause mortality at 30-days, 1-year and 5-years were associated with high NT-Pro BNP levels (HR 1.04, p = 0.046; HR 1.05, p = 0.002 and HR 1.04, p < 0.001), the presence of peripheral arterial disease (PAD) (HR 4.32, p = 0.056; HR 4.48, p = 0.006 and HR 2.43, p = 0.023) and chronic kidney disease (CKD) (HR 6.19, p = 0.006; HR 6.77, p < 0.001 and HR 2.09, p = 0.008). Society of Thoracic Surgery (STS) score (HR 1.11, p = 0.001; HR 1.13, p < 0.001 and HR 1.12, p < 0.001) and Valve Academic Research Consortium (VARC) III endpoints of acute kidney injury (AKI) (HR 6.68, p = 0.047, HR 10.8, p < 0.001 and HR 6.99, p < 0.001), cardiogenic shock (HR 26.3, p < 0.001, HR 12.0, p < 0.001 and HR 4.29, p = 0.011) and structural complications (HR 40.3, p < 0.001, HR 18.1, p < 0.001 and HR 5.18, p = 0.008) were associated with worse all –cause mortality at time-points of 30-days, 1-year and 5-years respectively. On multivariate analyses adjusted for comorbidities and outcomes, STS score and structural complications were independent predictors of 30-day, 1-year, and 5-year all-cause mortality (HR 1.16; p = 0.003, HR 1.09, p = 0.003 and HR 1.10, p < 0.001) and (HR 62.7, p < 0.007; HR 18.9, p < 0.001 and HR 10.6, p = 0.001) respectively. Angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) use was protective of survival within 1-year (HR 0.37, p = 0.022). Conclusions STS score and VARC III endpoints of structural complications were reliable predictors of all-cause mortality in Asian patients with TAVI. ACE inhibitor and ARB use was protective against mortality at 1-year.Cox regression analysesKaplan-Meier curves

Cardiovascular mortality with oral potassium-binders in patients with CKD and heart failure

Abstract Introduction Hyperkalemia is an inherent consequence of advancing chronic kidney disease (CKD) as a result of the kidney’s decreased ability to excrete potassium. Heart failure patients with concomitant CKD may not tolerate maximum doses of guideline-directed medical therapies (GDMT) like ACE inhibitors (ACEi), angiotensin receptor blockers (ARB), angiotensin receptor/neprilysin inhibitors (ARNI) and mineralocorticoid receptor antagonists (MRA) due to dose-limiting hyperkalemia. Many randomized controlled trials in heart failure exclude patients with advanced CKD. Two oral therapies exist to manage hyperkalemia - patiromer sorbitex calcium and sodium zirconium cyclosilicate. This study aims to identify the potassium-binder with better outcomes as defined by less readmissions, hyperkalemia episodes, and death. Purpose This project was undertaken to better understand the impact of using potassium-binders in CKD patients with heart failure. Improved management of hyperkalemia will be an avenue for optimization of GDMT in this population. Methods and materials The TriNetX research network was used for this study. Two cohorts of patients were created by using International Classification of Disease 10 (ICD-10) codes and CPT codes. Both cohorts consisted of patients with no prior history of hyperkalemia within 30 days of hospital discharge at which time one cohort was prescribed patiromer and the other received sodium zirconium cyclosilicate. Each cohort was prohibited from exposure to the other medication. The cohorts were balanced by propensity score matching and the greedy nearest neighbor algorithm for age, race, gender, ethnicity. They were also balanced for systolic and diastolic heart failure diagnoses, and for each individual stage of CKD (1 through 5 and end stage). They were also balanced for use of ACEi, ARBs, and MRAs. This resulted in 8,921 patients in each arm. They were then evaluated for the outcomes of hospital readmission, hyperkalemia episodes (>6.1 mmol/L), and death within 12 months. Results Patients treated with patiromer were more likely to be hospitalized over the following twelve months (44% vs 40%, RR 1.11, 95% CI (1.07,1.15), p value <0.0001). They were also more likely to experience hyperkalemia (11.7% vs 9.2%, RR 1.27, 95% CI (1.16,1.38), p value <0.0001). Patiromer was also associated with slightly greater all cause mortality (27% vs 25%, RR 1.08, 95% CI (1.03,1.13), p value 0.0021). Discussion This study demonstrates patiromer has more readmissions and hyperkalemia episodes along with greater mortality. In conclusion, sodium zirconium cyclosilicate was found to have better outcomes compared to that of patiromer. Further studies are necessary to better understand the utility of using sodium zirconium cyclosilicate as maintenance therapy for hyperkalemia in order to maximize GDMT in CKD patients with heart failure.

Elegibility for Sacubitril/Valsartan in italian clinical practice: insights from the OPTIMA-HF registry

Abstract Background/Introduction Guidelines strongly recommend patients with heart failure with reduced ejection fraction (HFrEF) be treated with multiple medications proven to improve clinical outcomes, as tolerated. Among them, angiotensin receptor blocker/neprylisin inhibitor (ARNi) are the foundation of neuro-hormonal blockade in patients with HFrEF, however the degree to which gaps in this medication use and dosing persist in outpatient practice is unclear. Purpose To assess the proportion of patients with HFrEF who are eligible for ARNi based on the PARADIGM-HF trial criteria and the association between eligibility and baseline characteristics. Methods The OPTIMA-HF (Optimization of Therapy in the Italian Management of Heart Failure) registry included outpatients in Italy with chronic HFrEF receiving at least 1 oral medication for management of HF. Patients were characterized by baseline use and dose of angiotensin-converting enzyme inhibitor (ACEI)/angiotensin II receptor blocker (ARB)/ARNI, beta-blocker, mineralocorticoid receptor antagonist (MRA) and sodium glucose co-transporter II inhibitor (SGLT2i). Patient-level factors associated with medication use were examined. Results Outpatients with HFrEF from 29 ambulatory cardiology practices and university hospitals in the OPTIMA-HF registry recruited between January 2022 and September 2023 were included. Of 1291 patients, 1018 (79%) met the PARADIGM-HF criteria and 949 of them (93%) were on ARNi. Of the enrolled patients, 342 (27%) were not on ARNi, however only 129 (38%) did not met the PARADIGM-HF inclusion criteria for ARNi prescription. Reasons for not meeting PARADIGM-HF criteria were no beta-blocker background therapy (22%), hyperkalemia (4%), hypotension (15%), chronic kidney disease (65%) and hyperkalemia (79%). In a logistic regression model not being on ARNi was associated with older age, chronic kidney disease, not being on cardiac resynchronization therapy, lower systolic blood pressure, lower BMI, and higher PAPs (Figure), representing the picture of a more fragile patient net of compliance with the PARADIGM-HF criteria. Conclusions Among outpatients with HFrEF in the OPTIMA-HF Registry, 79% met the PARADIGM-HF criteria. Strategies to improve guideline-directed use of HFrEF medications remain urgently needed, and these findings may inform targeted approaches to optimize outpatient medical therapy.

Guideline-directed medical therapy patterns in heart failure with reduced ejection fraction: the OPTIMA-HF registry

Abstract Background/Introduction European guidelines strongly recommend an optimized pharmacological treatment in patients with heart failure with reduced ejection fraction (HFrEF) with a fast introduction of the four-pillars. Purpose Aim of the Optimization of Therapy in the Italian Management of Heart Failure [OpTIMa-HF] Registry was to collect data on HF patients to describe the current Italian population of HF patients with a specific focus on HFrEF treatment adherence and prescription rates, according to the most recent European Guidelines. Methods OPTIMA-HF is an observational, cross-sectional, multicenter, real-life study conducted in two different clinical settings: HF outpatients’ clinics of Italian University Hospitals and territorial Italian Cardiology outpatients’ services, that enrolled patients with chronic HFrEF receiving at least 1 oral medication for management of HF. Patients were characterized by baseline use and dose of angiotensin-converting enzyme inhibitor (ACEI)/angiotensin II receptor blocker (ARB)/angiotensin receptor neprilysin inhibitor (ARNI), beta-blocker, mineralocorticoid receptor antagonist (MRA) and sodium glucose co-transporter II inhibitor (SGLT2i). Patient-level factors associated with medication use were examined. Results Overall, 1390 patients from 29 ambulatory cardiology practices and university hospitals were included. Mean age was 69.5 ± 11.9 years, 24% were female, and median EF was 33 (28-37). Among enrolled patients, 72.2% were prescribed ARNI, 17.1% ACEI/ARB, 95% beta-blocker, 75.5% MRA and 63% SGLT2i therapy (Figure 1). Despite high prescription rates for each single class, a still not sufficient number of patients was on treatment with all four pillars, in particular 40.4% considering the presence ARNI and 6.2%. When medications were prescribed, few patients were receiving target doses of ACEI/ARB (31.7%), ARNI (16%), and beta-blocker (33.3%), whereas a higher proportion were receiving target doses of MRA therapy (38%), and all were receiving target dose for SGLT2i. Among patients eligible for all classes of medication, only 1.1% were simultaneously receiving target doses of ACE/ARB/ARNI, beta-blocker, MRA and SGLT2i. Prescription rates did not significantly differ between the type of center (University Hospital vs. territorial Cardiology outpatients’ services). As regards patients not on treatment with any of the four pillars, a small but still present amount of patients had no contraindications to these drugs (Figure 1). Conclusions In this contemporary outpatient HFrEF Italian registry, significant high prescription rates of the four-pillars were observed, however therapy combination rate is still not sufficient and drugs' titration need to be implemented to receive the greatest benefits from an optimized treatment. Strategies to improve guideline-directed use of HFrEF medications remain urgently needed, and these findings may inform targeted approaches to optimize outpatient medical therapy.

ACE inhibitor and angiotensin receptor blocker use during pregnancy: data from the ESC Registry of pregnancy and cardiac disease (ROPAC)

Abstract Background and Aims Angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin receptor blockers (ARBs) are not recommended during the second and third trimester due to the significant risk of congenital anomalies associated with their use. However, data are scarce, especially regarding their use in the first trimester. Our study illustrates the profile of the women who used ACE-Is or ARBs during pregnancy and to evaluate the impact on perinatal outcomes. Methods The Registry of Pregnancy and Cardiac disease (ROPAC) is a prospective, global registry of pregnancies in women with structural heart disease. Outcomes were compared between women who used ACE-Is or ARBs and those who did not. Multivariable regression analysis was performed to assess the effect of ACE-I or ARB use on the occurrence of congenital anomalies. In addition, the perinatal outcomes of patients who stopped ACE-Is and/or ARBs before pregnancy were assessed. Results ACE-I (n=35) and/or ARB (n=8) were used in 42 (0.7%) of the 5739 ROPAC pregnancies. Women who used ACE-Is or ARBs more often came from a low-or-middle-income country (57% vs 40%, p=0.021), had chronic hypertension (31% vs 6%, p<0.001), or a left ventricular ejection fraction <40% (33% vs 4%, p<0.001). No pregnancy terminations due to fetal anomaly were reported. ACE-I use during the first trimester was independently associated with an increased risk of congenital anomaly (OR 3.1; 95% CI 1.0-9.3). No adverse fetal or neonatal effects were seen when ACE-I and/or ARB were discontinued prior to pregnancy. Conclusions ACE-Is and ARBs are seldom used during pregnancy and based on our data, ACE-Is should also be avoided in the first trimester due to a higher risk of congenital anomalies. Preconception counseling is crucial to discuss the potential risks of these medications, and to evaluate the clinical condition and, if possible, the woman can be switched to an alternative medication.

ACE Inhibitors and Angiotensin Receptor Blockers for the Primary and Secondary Prevention of Cardiovascular Outcomes: Recommendations from the 2024 Egyptian Cardiology Expert Consensus in Collaboration with the CVREP Foundation.

The renin-angiotensin-aldosterone system (RAAS) plays a pivotal role in regulating blood pressure (BP), with dysregulation of RAAS resulting in hypertension and potentially heart failure (HF), myocardial infarction (MI), cardio-renal syndrome, and stroke. RAAS inhibitors, such as angiotensin-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs), have advantages beyond BP control. However, differences between these two drug classes need to be considered when choosing a therapy for preventing cardiovascular events. A panel of 36 Egyptian cardiologists developed consensus statements on RAAS inhibitors for primary and secondary prevention of cardiovascular outcomes and stroke, using a modified three-step Delphi process. The consensus statements highlight the importance of effective BP control and the role of RAAS blockade for prevention and management of various cardiovascular diseases. ACEis and ARBs differ in their mode of action and, thus, clinical effects. On the basis of available evidence, the consensus group recommended the following: ACEis should be considered as first choice (in preference to ARBs) to reduce the risk of MI, for primary prevention of HF, and for secondary prevention of stroke. ACEis and ARBs show equivalent efficacy for the primary prevention of stroke. Evidence also favors the preferential use of ACEis in patients with type 2 diabetes, for BP control, for the primary prevention of diabetic kidney disease, and to reduce the risk of major cardiovascular and renal outcomes. Treatment with an ACEi should be started within 24 h of ST segment elevation MI (and continued long term) in patients with HF, left ventricular systolic dysfunction, and/or diabetes. Angiotensin receptor/neprilysin inhibitors (ARNIs) are the first choice for patients with HF and reduced ejection fraction, with ACEis being the second choice in this group. ARBs are indicated as alternatives in patients who cannot tolerate ACEis. ACEis may be associated with cough development, but the incidence tends to be overestimated, and the risk can be reduced by use of a lipophilic ACEi or combining the ACEi with a calcium channel blocker. RAAS blockade is an essential component of hypertension therapy; however, the protective effects provided by ACEis are superior to those of ARBs. Therefore, an ACEi is indicated in almost all cases, unless not tolerated.

Renin–angiotensin system inhibition and mortality in patients undergoing dialysis with coronary artery disease: insights from a multi-center observational study

ABSTRACT Background While the survival benefits of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) are firmly established in the general population, their efficacy within patient undergoing dialysis with coronary artery disease (CAD) remains controversial. Methods Between January 2015 and June 2021, 1168 patients undergoing dialysis with CAD were assessed from 30 tertiary medical centers. The primary outcome was all-cause death, and the secondary outcome was cardiovascular death. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for between-group differences. Results Overall, ACEI or ARB were prescribed to 518 patients (44.3%) upon discharge. After a median follow-up of 22.2 months, 361 (30.9%) patients died, including 243 cardiovascular deaths. The use of ACEI or ARB was associated with a significantly lower risk of all-cause (25.3% vs 35.4%, hazard ratio [HR] 0.65, 95% confidence interval [CI] 0.52–0.82, p < 0.001) and cardiovascular death (17.0% vs 23.8%; HR 0.64, 95% CI 0.48–0.83, p = 0.001). These findings remained consistent across IPTW and PSM analyses. Sensitivity analyses for ACEI and ARB use separately yielded similar results. Conclusions Our findings suggested that among patients undergoing dialysis with CAD, ACEI or ARB use was associated with a lower risk of all-cause and cardiovascular death.

Advancing Community Care and Access to Follow-Up after Acute Kidney Injury Hospitalization: A Randomized Clinical Trial.

Key Points A risk-guided intervention improved adherence to processes of care for AKI survivors.Further supports are necessary to improve uptake of processes of care for AKI survivors in primary care. Background AKI is associated with development and progression of CKD. Gaps in recommended care for CKD are common after AKI. Methods In this randomized controlled trial conducted in Alberta, Canada, we allocated adults hospitalized with Kidney Disease Improving Global Outcomes (KDIGO) stage 2 or greater AKI to a risk-guided, transition of care intervention versus usual practices at the time of hospital discharge. For people in the intervention group, we used a validated risk index to predict risk of severe CKD after AKI. People at low risk (&lt;1%) received patient education alone. People at medium risk received additional clinical guidance, provided to their primary care physician. People at high risk (&gt;10%) were referred to nephrology. The primary outcome was the proportion of patients who received treatment with an angiotensin-converting enzyme inhibitor (ACE-I) or angiotensin II receptor blocker (ARB), statin, and nephrology specialist follow-up within 90 days of discharge. Results One hundred fifty-five patients were recruited; the mean (SD) age was 60 (15) years, 91 (60%) were male, and 96 (62%) had eGFR &lt;60 ml/min per 1.73 m2 or urine albumin-creatinine ratio &gt;30 mg/g at discharge. The proportion of participants who received ACE-I/ARB, statin treatment, and nephrologist follow-up was 28% in the intervention group versus 3% in the usual care group (absolute risk difference [RD], 25%; 95% confidence interval [CI], 15% to 36%). The use of ACE-I or ARB in participants with urine albumin-creatinine ratio &gt;300 mg/g or diabetes was greater in the high-risk group with the intervention versus usual care (RD, 37%; 95% CI, 6% to 67%), as was statin use among those with CKD (RD, 30%; 95% CI, 5% to 56%) and nephrologist follow-up for those with sustained eGFR &lt;30 ml/min per 1.73 m2 at discharge (RD, 78%; 95% CI, 56% to 100%). Hyperkalemia was more frequent in the intervention group (RD, 10%; 95% CI, 9% to 19%). Conclusions A risk-guided intervention for patients hospitalized with AKI increased recommended processes of care for CKD for high-risk patients after hospital discharge. Clinical Trial registry name and registration number: Improving Post Discharge Care after Acute Kidney Injury (AFTER AKI), NCT02915575.

Use of renin-angiotensin system blockers and posttraumatic stress disorder risk in the UK Biobank: a retrospective cohort study

BackgroundPrevious research has shown that the use of renin-angiotensin system (RAS) blockers is linked to a lower prevalence of posttraumatic stress disorder (PTSD), but longitudinal studies are scarce. We aimed to estimate the association between the use of RAS blockers and the risk of PTSD among individuals taking antihypertensive medications.MethodsThis longitudinal study included participants aged 40–69 from the UK Biobank. Exposure data were obtained from the initial assessment (2006–10), while outcome data were obtained from the online mental health questionnaire administered 6–11 years later (2016–17). We included participants who were under antihypertensive treatment and did not have a prior diagnosis of PTSD before the initial assessment. Use of RAS blockers was defined as self-reported regular use, at the initial assessment, of angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB). Among participants who experienced adverse life experiences, cases of probable PTSD were defined with the six-item PTSD Checklist-Civilian version score ≥ 14. Logistic regression with inverse probability of treatment weighting was used to estimate the odds ratios (ORs) and 95% confidence interval (CI) for the association between RAS blocker use and the risk of probable PTSD.ResultsOf the 15,954 participants (mean age = 59.9 years; 42.6% women) under antihypertensive treatment with no prior history of PTSD at the initial assessment, 64.5% were taking RAS blockers. After a mean follow-up of 7.5 years, 1,249 (7.8%) were newly identified with probable PTSD. RAS blocker users had a lower risk of probable PTSD than RAS blocker non-users (OR = 0.84 [95% CI: 0.75–0.94]), whereas the use of other antihypertensive medications showed no such association (users vs. non-users; calcium channel blockers, OR = 0.99 [95% CI: 0.88–1.11]; beta-blockers, 1.20 [1.08–1.34]; and thiazide-related diuretics, 1.15 [1.03–1.29]). The association between probable PTSD risk and the use of ACEi vs. ARB showed no significant difference (p = 0.96).ConclusionsAmong individuals under antihypertensive treatment, the use of RAS blockers was associated with a decreased risk of probable PTSD. This added benefit of RAS blockers should be considered in the selection of antihypertensive medications.

Genetics in nephrology - any news?

While genetic kidney diseases were long regarded as a rare cause of kidney failure, it has been shown in recent years that they account for a relevant proportion of cases. In cohorts of kidney transplant recipients, a monogenic cause is found in up to 30% of cases. Identifying the genetic cause of kidney disease has become much easier thanks to technological advances in DNA sequencing. The focus has now shifted to understanding the significance of the findings and identifying diagnostic gaps. It is still not possible to clarify all CKD cases of unclear aetiology. Besides very effective generic treatments for monogenic kidney disease (e.g., ACE-inhibitor use in Alport Syndrome), increasing knowledge of the pathophysiology of genetic kidney diseases has led to a growing number of targeted therapies. These include the treatment of ADPKD with Tolvaptan, which has now been in use for 10 years. Recently, exciting, and completely new approaches have been added, such as the first siRNA therapies in nephrology for primary hyperoxaluria type 1, the targeted treatment of hyperphagia in Bardet-Biedl syndrome, the therapy of APOL1-associated kidney disease or the use of the HIF-2 antagonist Belzutifan for renal cell carcinoma associated with Von-Hippel-Lindau syndrome. The new possibilities in the treatment of patients with genetic kidney diseases have also clearly revealed deficits in current patient care. Centers of excellence with extensive experience in this area therefore play an important role in improving care. This also applies to the further training of colleagues in the field. In Germany, the National Action Alliance for People with Rare Diseases (NAMSE) and the nationwide establishment of - to date - 36 centers for rare diseases play an important role in this regard.

Computational assessment of targeting angiotensin-converting enzyme for hypertension management: A structure-based virtual screening approach

Background: Hypertension is a growing public health concern globally. The angiotensin-converting enzyme (ACE) is an enzyme that cleaves the carboxy-terminal His-Leu dipeptide from angiotensin I, yielding the potent vasopressor octapeptide, angiotensin II. ACE inhibitors are a primary treatment option for hypertension, heart failure, and myocardial infarction. However, the use of synthetic ACE inhibitors has been linked to a number of side effects. Therefore, the development of novel and safe ACE inhibitors is a need of time.Methods: This study used a computational screening of a library of known compounds with anti-inflammatory activities against the active site of ACE using the PyRx-Python 0.8 tool to find more potent ACE inhibitors with less or no side effects. The physicochemical properties of the anti-inflammatory compounds were obtained from the Life Chemicals website.Result: The five hits, specifically F3398-2114, F0193-0245, F0163-0089, F0193-0237, and F0302-0060, exhibited notable interactions within the ACE binding pocket and demonstrated greater binding energy compared to the control compound, Lisinopril. All of these compounds displayed favorable physicochemical characteristics and aligned to Lipinski's rule.Conclusion: The compounds F3398-2114, F0193-0245, F0163-0089, F0193-0237, and F0302-0060 have the potential to be used as ACE inhibitors; however, further experimental validation is required to optimize them as ACE inhibitors.Keywords: Hypertension; Angiotensin-converting enzyme; Heart failure; Lipinski's rule

ACEIs in high blood pressure: friend or enemy?

Optimal blood pressure control has been one of the fundamental objectives of primary care physicians and other medical specialties for many years. ACEIs (angiotensin-converting enzyme inhibitors) are one of the families of medications with an antihypertensive effect with the greatest experience in their use over decades. A 70-year-old patient previously diagnosed with high blood pressure and treated with ACEI, began in January 2013 with progressive worsening of kidney function.There are several mechanisms by which ACEIs produce an AKF (Acute Kidney Failure), such as efferent arteriolar vasodilatation because of blocking Angiotensin 2 effect or inmunoallergic mechanisms, or even different pathologies that could trigger it (congestive heart failure, liver cirrhosis with ascites and in presence of bilateral renal stenosis or unilateral stenosis of a single functioning kidney). The use of ACEIs as a first-line treatment for high blood pressure is supported by diverse clinical guidelines and by excellent results in a broad profile of patients. In a small percentage of cases, they have shown adverse effects that can affect the functioning of several systems involved in the correct control of the patient's cardiovascular risk, such as the renal system.

Association of RAAS inhibitors on osteoporosis and fracture risk in the hypertensive population–A prospective population-based cohort study in Lanzhou, China

BackgroundRenin-angiotensin-aldosterone system (RAAS) inhibitors appear to benefit bone tissue in antihypertensive treatment. However, the association between RAAS inhibitors and bone metabolism was inconsistent.Methods and study designBased on the study of Risk Evaluation of Cancers in Chinese Diabetic Individuals(REACTION) conducted in 2011, We followed 6,252 Lanzhou residents aged 40–75 years from 2014 to 2016. Finally, 1,625 hypertension cases with complete data were included in the analysis. The study subjects were divided into four groups according to the type of antihypertensive drugs. We employed logistic or multivariate Cox proportional hazards regression to estimate the association between different antihypertensive drug use and osteoporosis, the risk of fracture, and the change in bone mineral density (BMD) level. The association of osteoporosis or the fracture risk by cumulative duration of use of these medications (< 3 years.) and (> 3 years.) was also estimated.ResultsThe cross-sectional study showed that there was no significant association between baseline antihypertensive drugs (angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB)) use and osteoporosis and fracture. During a mean follow-up of 3.4 years in the longitudinal study, there were 478 new osteoporosis cases and 76 fractures. Compared with patients without antihypertensive drug use, the hazard ratios (HRs) [95% confidence interval (CI)] for the risk of osteoporosis were 1.005(0.651,1.552) and 1.077(0.793,1.462) in ACEI or ARB use (p > 0.05). ACEI or ARB use was also not significantly associated with fracture risk (HR 1.102(0.326,3.726), 0.735(0.251,2.148), p > 0.05). Further analysis showed that the use of ACEI (HR 1.078(0.146,7.950)) or ARB (HR 1.169(0.347,3.939)) was not significantly associated with the improvement of osteoporosis (p > 0.05). In addition, the duration of RAAS inhibitors used showed no apparent correlation with the risk of osteoporosis (≤ 3 years: HR 0.872 (0.516, 1.474), > 3 years: HR 1.151 (0.574, 2.308)), nor with the improvement of osteoporosis and the risk of fracture. Meanwhile, the association mentioned above did not change compared to different RAAS inhibitors.ConclusionsThe use of RAAS inhibitors, including ACEIs and ARBs, was not significantly associated with osteoporosis, risk of fracture, or BMD change.

Angiotensin-converting enzyme inhibitors: a therapeutic option for controlling blood pressure associated with delayed cognitive processing speed.

Antihypertensive treatment (AT) is essential for preventing hypertension-related cognitive decline. The goals of this observational study were to compare cognitive performance (CP) between non-hypertensive (NH) volunteers and hypertensive patients and to evaluate the correlation between CP and antihypertensive drugs (AHD). Three groups were constituted: NH (n = 30) [group 1], hypertensive with systolic blood pressure (SBP) < 140 mmHg and diastolic blood pressure (DBP) < 90 mmHg (n = 54) [group 2] and hypertensive with SBP ≥ 140 or DBP ≥ 90 (n = 31) [group 3]. To analyze the cognitive domains, a neuropsychological battery was applied and the raw performance values in these tests were transformed into z-scores. The domain was considered impaired if it presented a z-score below -1.5 SD. Compared to group 1, both groups of hypertensive were older (51 [ ± 12] years) and showed a worse CP in episodic memory (p = 0.014), language (p = 0.003) and processing speed (PS) [p = 0.05]. Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) were the most used AHD (46.3%, p = 0.01 [group 2] and 64.5%, p = 0.005 [group 3]) and showed correlations with PS. Linear regression models revealed a negative association of PS with the use of ACEi (β = -0.230, p = 0.004), but not with the use of ARB (β = 0.208, p = 0.008). The effect of AT on cognition appears to go beyond the search for lower blood pressure targets and also includes the mechanism of action of AHD on the brain, so that additional benefits may possibly be achieved with simple adaptations in the treatment regimen, particularly in patients without clinically manifest cognitive impairment.

Effectiveness and risk of ARB and ACEi among different ethnic groups in England: A reference trial (ONTARGET) emulation analysis using UK Clinical Practice Research Datalink Aurum-linked data.

Guidelines by the National Institute for Health and Care Excellence recommend an angiotensin receptor blocker (ARB) rather than an angiotensin-converting enzyme inhibitor (ACEi) for the treatment of hypertension for people of African and Caribbean descent, due to an increased risk of angioedema associated with ACEi use observed in US trials. However, the effectiveness and risk of these drugs in Black populations in UK routine care is unknown. We applied a reference trial emulation approach to UK Clinical Practice Research Datalink Aurum data (linked with data from Hospital Episode Statistics and Office for National Statistics) to study the comparative effectiveness of ARB and ACEi in ethnic minority groups in England, after benchmarking results against the ONTARGET trial. Approximately 17,593 Black, 30,805 South Asian, and 524,623 White patients receiving a prescription for ARB/ACEi between 1 January 2001 and 31 July 2019 were included with a median follow-up of 5.2 years. The primary composite outcome was cardiovascular-related death, myocardial infarction, stroke, or hospitalisation for heart failure with individual components studied as secondary outcomes. Angioedema was a safety endpoint. We assessed outcomes using an inverse-probability-weighted Cox proportional hazards model for ARB versus ACEi with heterogeneity by ethnicity assessed on the relative and absolute scale. For the primary outcome, 27,327 (18.0%) events were recorded in the ARB group (event rate: 25% per 5.5 person-years) and 80,624 (19.1%) events (event rate: 26% per 5.5 person-years) in the ACEi group. We benchmarked results against ONTARGET and observed hazard ratio (HR) 0.96 (95% CI: 0.95, 0.98) for the primary outcome, with an absolute incidence rate difference (IRD)% of -1.01 (95% CI: -1.42, -0.60) per 5.5 person-years. We found no evidence of treatment effect heterogeneity by ethnicity for the primary outcome on the multiplicative (Pint = 0.422) or additive scale (Pint = 0.287). Results were consistent for most secondary outcomes. However, for cardiovascular-related death, which occurred in 37,554 (6.6%) people, there was strong evidence of heterogeneity on the multiplicative (Pint = 0.002) and additive scale (Pint < 0.001). Compared to ACEi, ARB were associated with more events in Black individuals (HR 1.20 (95% CI: 1.02, 1.40); IRD% 1.07 (95% CI: 0.10, 2.04); number-needed-to-harm (NNH): 93) and associated with fewer events in White individuals (HR 0.91 (95% CI: 0.88, 0.93); IRD% -0.87 (95% CI: -1.10, -0.63); number-needed-to-treat (NNT): 115), and no differences in South Asian individuals (HR 0.97 (95% CI: 0.86, 1.09); IRD% -0.17 (95% CI: -0.87, 0.53)). For angioedema, HR 0.56 (95% CI: 0.46, 0.67) with no heterogeneity for ARB versus ACEi on the multiplicative scale (Pint = 0.306). However, there was heterogeneity on the additive scale (Pint = 0.023). Absolute risks were higher in Black individuals (IRD% -0.49 (95% CI: -0.79, -0.18); NNT: 204) compared with White individuals (IRD% -0.06 (95% CI: -0.09, -0.03); NNT: 1667) and no difference among South Asian individuals (IRD% -0.05 (95% CI: -0.15, 0.05) for ARB versus ACEi. These results demonstrate variation in drug effects of ACEi and ARB for some outcomes by ethnicity and suggest the potential for adverse consequences from current UK guideline recommendations for ARB in preference to ACEi for Black individuals.

Impact of ACEI/ARB use on the survival of hypertensive patients with cancer: A meta‑analysis.

Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are commonly used antihypertensive drugs. However, the impact that the use of ACEI and ARB drugs will have on the survival of patients with hypertension and cancer is still unclear. Therefore, the present study aimed to investigate the effects of ACEI and ARB use on the survival of patients with cancer. The Embase, PubMed and Web of Science databases were used to systematically analyze the survival of hypertensive patients with cancer treated with ACEIs or ARBs. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to evaluate the association between ACEI and ARB use and patient survival. The relationship between the survival of patients with certain types of cancer and ACEI and ARB use was evaluated using the calculated HRs. Patients with ovarian, pancreatic, prostate, hepatocellular, lung, esophageal, gastric, colon, nasopharyngeal, head and neck tumors, gallbladder and rectal cancers that used ACEI and ARB analogs had significantly increased survival times, except for patients with breast cancer (HR, 1.04; 95% CI, 0.90-1.19; P<0.01) and uroepithelial carcinoma (HR, 1.15; 95% CI, 0.69-1.94; P<0.01), who had significantly decreased survival times, when compared with patients who did not use these drugs. Analysis of the relationship between the use of ACEIs or ARBs alone or in combination on the overall survival of hypertensive patients with cancer demonstrated that the use of ACEIs alone (HR, 1.00; 95% CI, 0.93-1.08; P<0.01) did not have a significant effect on the survival of these patients. By contrast, the survival time was increased in hypertensive patients with cancer who used either ARBs alone (HR, 0.89; 95% CI, 0.84-0.94; P<0.01) or a combination of ACEIs and ARBs (HR, 0.84; 95% CI, 0.78-0.91; P<0.01). The present meta-analysis demonstrated the potential effects of ACEI and ARB use on the overall survival of patients with cancer. Therefore, investigation of the underlying mechanisms of action of ACEIs and ARBs, as well as the identification of specific groups of patients who may benefit from these interventions, could potentially lead to novel therapeutic options and improve the prognosis of patients with cancer in the future.

Association of SLCO1B1 gene variants with angiotensin-converting enzyme inhibitor-induced cough in a Pakistani hypertensive cohort.

Angiotensin-converting enzyme inhibitors (ACEIs) are prescribed for individuals with high cardiovascular (CV) risk; however, persistent cough limits the use of ACEIs in a large number of patients. The current study aimed to identify the genetic variants in the SLCO1B1 gene that might be associated with ACEI-related cough in a Pakistani hypertensive population. A prospective cohort study was conducted at a tertiary care hospital in Pakistan. A total of 74 patients who had been treated with ACEIs were recruited through a convenient sampling method. The study was approved by the Institutional Review Board & Ethics Committee of the Shifa International Hospital, Islamabad. Patients provided 2ml of blood for sequencing after signing informed consent. Partial gene sequencing of SLCO1B1 was carried out to find single nucleotide polymorphisms (SNPs) and haplotypes. It was found, through a structured questionnaire, that thirty-eight (38) patients experienced cough within 2weeks of ACEI administration and were considered as a case group (cough), and thirty-six (36) patients were considered as a control group (no cough). The incidence of cough was 51%. We found six different SNPs and 9 haplotypes in the partial gene sequences of SLCO1B1. Haplotype H4 was associated significantly with cough after adjusting for sex and smoking status. Other SNPs and haplotypes were not significantly associated with ACE-Is-induced cough. These findings emphasize the significance of SLCO1B1 genetic variants, specifically H4, as a potential predictor of ACEI-induced cough. It could be included in clinical practice as a possible risk factor for ACEI-induced cough once confirmed in larger clinical trials with bigger sample sizes. The replication of these findings in larger and more diverse populations is likely to contribute to the therapeutic use of ACEIs by predicting ACEI-induced cough.