Angiotensin Receptor Blockers Research Articles

Angiotensin-converting enzyme 2 and AMPK/mTOR pathway in the treatment of liver fibrosis: Should we consider further implications?

This editorial contains comments on the article by Zhao et al in print in the World Journal of Gastroenterology . The mechanisms responsible for hepatic fibrosis are also involved in cancerogenesis. Here, we recapitulated the complexity of the renin-angiotensin system, discussed the role of hepatic stellate cell (HSC) autophagy in liver fibrogenesis, and analyzed the possible implications in the development of hepatocarcinoma (HCC). Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers definitively contribute to reducing hepatic fibrogenesis, whereas their involvement in HCC is more evident in experimental conditions than in human studies. Angiotensin-converting enzyme 2 (ACE2), and its product Angiotensin (Ang) 1-7, not only regulate HSC autophagy and liver fibrosis, but they also represent potential targets for unexplored applications in the field of HCC. Finally, ACE2 overexpression inhibits HSC autophagy through the AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway. In this case, Ang 1-7 acts binding to the MasR, and its agonists could modulate this pathway. However, since AMPK utilizes different targets to suppress the mTOR downstream complex mTOR complex 1 effectively, we still need to unravel the entire pathway to identify other potential targets for the therapy of fibrosis and liver cancer.

Association between types of antihypertensive medication and the risk of atrial fibrillation: a nationwide population study

BackgroundPatients with hypertension are at a high risk of atrial fibrillation (AF). Recent research has indicated the varying effects of antihypertensive medications on developing AF.ObjectivesWe investigated the relationship between different types of antihypertensive medications and the risk of AF occurrence.MethodsWe analyzed data from 113,582 subjects with national health screening examinations between 2009 and 2014. The study population was categorized according to antihypertensive medication type. The primary outcome was the incidence of AF.ResultsAmong 113,582 subjects (mean age 59.4 ± 12.0 years, 46.7% men), 93,557 received monotherapy [angiotensin receptor blockers (ARB), angiotensin-converting enzyme inhibitors (ACEi), beta-blockers, calcium channel blockers (CCB), or diuretics], while 34,590 received combination therapy (ARB/beta-blockers, ARB/CCB, ARB/diuretics, or ARB/CCB/diuretics). During a mean follow-up duration of 7.6 ± 2.1 years, 3.9% of patients were newly diagnosed with AF. In monotherapy, ACEi and CCB had similar AF risks as ARB, while beta-blockers and diuretics showed higher AF risks than ARB. In combination therapy, ARBs/CCBs and ARBs/diuretics had the lowest AF risk, whereas ARBs/beta-blockers had the highest compared to ARB/CCB. Among the specific ARBs, the AF risk varied insignificantly, except for telmisartan and candesartan.ConclusionsIn hypertensive patients receiving monotherapy, ACEi and CCB showed a similar AF risk as ARBs, while beta-blockers and diuretics were associated with a higher risk. Among those receiving combination therapy, ARBs/CCBs and ARBs/diuretics had the lowest AF risk, whereas ARBs/beta-blockers showed the highest risk. Various types of ARBs have different associations with AF risk.

CLINICAL RELEVANCE OF HIGH SENSITIVITY C-REACTIVE PROTEIN IN ACUTE MYOCARDIAL INFARCTION PATIENTS

Objectives: Poor cardiovascular outcomes have been linked to high-sensitivity C-reaction protein (hs-CRP), a biomarker of residual inflammatory risk. Whether or not a patient has diabetes mellitus, evaluate the relationship among hs-CRP levels estimated at hospital admission and in-hospital consequences and death. Methods: This prospective cohort study included 100 acute myocardial infarction (AMI) patients with both non-ST elevation myocardial infarction (STEMI) and STEMI who were admitted to the cardiac care critical care unit intensive therapy unit. Results: Diabetics had a considerably higher incidence of hypertension (p=0.001) and dyslipidemia (p=0.001) compared to non-diabetics. Diabetics exhibited a significantly higher mean hs-CRP level (6.76±1.12 vs. 3.65±0.98 mg/dL; p=0.01) than non-diabetics. Meanwhile, compared to non-diabetics, diabetics utilized significantly more aspirin (p=0.001), beta-blockers (p=0.001), angiotensin receptor blockers (ARBs) (p=0.01), and statins (p=0.001). Furthermore, compared to those with hs-CRP <3 mg/L, those with hs-CRP ≥3 mg/dL had a significantly higher incidence of dyslipidemia (p=0.001) and hypertension (p=0.001). Conclusion: The results of the current study demonstrated that hs-CRP upon admission is a valid predictor of hospital morbidity and death in patients with AMI who are diabetic or non-diabetic. Individuals with diabetes showed greater CRP levels than non-diabetic AMI patients did.

Effect of beta-blockers and angiotensin receptor blockers in reducing the aortic growth rate in children with bicuspid aortic valve-related aortopathy

AimsThe aim of this study is to evaluate the effect of beta-blockers and angiotensin receptor blockers in reducing the aortic growth rate in children with bicuspid aortic valve (BAV)-related aortopathy and ascending phenotype. MethodsConsecutive paediatric patients (≤16 years) with BAV and ascending aorta (AsAo) dilation (z-score > 3) were enrolled in this observational retrospective cohort study. Patients receiving prophylactic treatment with either atenolol (0.5 to 1.0 mg/kg/daily) or losartan (0.7 to 1.4 mg/kg/daily) were compared with those who did not receive medical prophylaxis (control group). The primary outcome of interest was the annual rate of change in maximal AsAo diameter z-score in the treatment and control groups. ResultsFrom a cohort of 1005 patients, 120 (mean age 11.3 ± 4.5 years, 82% males) fulfilled the inclusion criteria and were included in the study. Patients in the treatment and control group had similar age, sex, family history of BAV, BAV morphology, and baseline AsAo diameter. During a median follow-up of 7.1 years (interquartile range 3.8–10.2), no differences were observed in the annual growth rate of aortic diameter z-score between patients on treatment and controls. The prevalence of aortic diameter progression was similar in the treatment and control groups, and treatment with atenolol or losartan was not associated with a lower rate of aortic disease progression. ConclusionsThe findings revealed no significant difference in the annual aortic growth rate between treated and untreated patients. Larger cohort studies or, ideally, randomized clinical controlled trials are needed to validate these findings.

Medullary sponge kidney with IgA nephropathy: a case report and literature review

BackgroundMedullary sponge kidney (MSK)is rare in association with glomerulonephritis. We report a patient with medullary sponge kidney, and the kidney biopsy revealed a diagnosis of IgA nephropathy.Case presentationA 27-year-old female presented with hematuria and proteinuria, and imaging studies indicated the presence of medullary spongy kidney. With appropriate preparation, a kidney biopsy was performed. Considering the patient’s clinical and pathological characteristics, the final diagnosis was determined to be medullary sponge kidney associated by IgA nephropathy. The combination of corticosteroids and angiotensin receptor blockers (ARBs) proved to be significantly effective in reducing proteinuria in the current case. To the best of our knowledge, this is the first reported case that demonstrates the coexistence of MSK and IgA nephropathy.ConclusionsAdministering precise therapy based on renal pathology can potentially enhance outcomes for patients with renal conditions, necessitating the need for clinicians to be vigilant about differential diagnosis in order to reduce the rates of missed diagnoses and misdiagnosis.

Novel Insights in the Hypertension Treatment & Type 2 Diabetics Induced by Angiotensin Receptor Blockers: MD Simulation Studies & Molecular Docking of Some Promising Natural Therapies

Novel Insights in the Hypertension Treatment & Type 2 Diabetics Induced by Angiotensin Receptor Blockers: MD Simulation Studies & Molecular Docking of Some Promising Natural Therapies

Abstract PO3-24-10: Losartan enhances the radiosensitivity of triple-negative breast cancer by reshaping the tumor immune microenvironment

Abstract Triple-negative breast cancer (TNBC) represents the most aggressive subtype of breast cancer, and the therapeutic options available for TNBC are limited. In addition to surgery and chemotherapy, radiotherapy (RT) is a primary treatment modality for TNBC. However, radio-resistance poses significant challenges to TNBC treatment. Prior research has shown that losartan, an angiotensin receptor blocker, can improve vessel perfusion and drug delivery, thereby enhancing the efficacy of chemotherapy or radiotherapy in cancer. However, in our study, we found that losartan could enhance the radiosensitivity of TNBC in immunocompetent mice model, but not in immunodeficient mice model and TNBC cells. It suggested that losartan might enhance the radiosensitivity of TNBC in an immune system dependent way. Previous studies had noted that tumor immune microenvironment (TIME) played an important role in radio-resistance. Therefore, we focused on the TIME in our further study. For immune cells, it had reported that the recruitment and activation of immunosuppressive cells such as M2 phenotype tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs), could lead to the establishment of and immunosuppressive TIME and decreased the radiosensitivity. In this study, we found losartan facilitated the polarization of TAMs towards the M1 phenotype, and impeded the immunosuppressive function of MDSCs after RT in 4T1 TNBC mice model. Additionally, losartan also caused a significant increase of CD8+ T lymphocytes in the TIME, and also markedly enhanced the activity of infiltrated T cell. When the CD8+ T cells were eliminated by anti-CD8α antibody, the radiosensitization effect of losartan was significantly decreased. Therefore, T-cell mediated tumor suppression is essential for the radiosensitization caused by losartan in TNBC. For immune factors, we found that TNBC exhibited an increase in the expression of programmed death-ligand (PD-L1) and indoleamine-2,3-dioxygenase (IDO) upon exposure to irradiation, and the combination of losartan resulted in a significant reduction in their expression in vitro and in vivo. At the same time, the 4T1 TNBC transplantation tumors were significantly inhibited by losartan combined with PD-1 inhibitor after RT, which indicated that losartan might amplify the efficacy of radio-immunotherapy. Collectively, these findings suggest that losartan could reshape the TIME of TNBC through regulating immune cells (TAMs, MDCSs and CD8+ T cells) and immune factors (PD-L1 and IDO), which result in the enhancement of radiosensitivity of TNBC. In our investigation, losartan was innovatively found to increase the radiosensitivity of TNBC by reshaping the TIME rather than on the tumor stroma. As one of the most commonly prescribed drugs for hypertension, the safety and affordability of losartan have been extensively confirmed. In the future, losartan combined with radiotherapy might be a promising strategy for TNBC treatment. Citation Format: Cuiwei Liu, Xu Wang, Zihan Xia, Yuxi Ma, Yanxia Zhao. Losartan enhances the radiosensitivity of triple-negative breast cancer by reshaping the tumor immune microenvironment [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-24-10.

The Effect of Renin-Angiotensin-Aldosterone System Blocking Agents on the Long-term Disease Course of Patients With Crohn's Disease.

The renin-angiotensin-aldosterone system (RAAS) has been associated with gastrointestinal inflammation and fibrosis, suggesting that RAAS blockade may be beneficial in patients with inflammatory bowel disease. Using retrospective analysis, we aimed to compare the disease course of patients with Crohn's disease (CD) taking two commonly prescribed classes of RAAS-blocking agents. Patients with CD initiated on an angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) between 2000 and 2016 were enrolled. Data on clinical, radiologic, and procedural surrogate markers of inflammatory bowel disease were collected in the subsequent 3, 5, and 10 years and compared with matched controls using univariate and multivariate analyses. Compared with controls, patients taking ARBs had fewer instances of corticosteroid use (1.06 vs 2.88, P < 0.01) at 10 years. Patients taking ACEIs had an overall worse disease course, with more imaging studies (3.00 vs 1.75, P = 0.03) and endoscopic procedures (2.70 vs 1.78, P = 0.01) at 5 years, and more imaging studies (6.19 vs 3.50, P < 0.01), endoscopic procedures (5.91 vs 3.78, P < 0.01), and gastrointestinal operations (0.59 vs 0.18, P < 0.02) at 10 years. Results remained significant on multivariate analysis, adjusting for CD characteristics and the use of other antihypertensive medications. Our study provides insight into the long-term use of RAAS-blocking agents in patients with CD, suggesting that differences exist among commonly prescribed medication classes. While ACEIs were associated with an overall worse disease course at 5 and 10 years, patients taking ARBs were noted to have fewer instances of corticosteroid use at 10 years. Future large-scale studies are needed to further explore this association.

Angiotensin-Converting Enzyme Inhibitors or Angiotensin Receptor Blockers After Transcatheter Aortic Valve Replacement: A Meta-Analysis

BackgroundPersistent left ventricular hypertrophy after transcatheter aortic valve replacement (TAVR) has been associated with poor outcomes. Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), due to their favorable effects on ventricular remodeling, have been hypothesized to improve outcomes post-TAVR, yet there are no recommendations regarding their use. ObjectivesThis study aimed to compare the outcomes of patients receiving ACEIs/ARBs with those not receiving ACEIs/ARBs after TAVR. MethodsWe performed a literature search on PubMed and Cochrane Library until June 14, 2023, and included all studies comparing clinical outcomes between patients given ACEIs/ARBs and those not given ACEIs/ARBs after TAVR. All-cause mortality was the primary outcome. We used a random effects model with appropriate corrections to calculate relative risk (RR) and CIs, with all analyses carried out using R v4.0.3. ResultsWe included ten studies on the use of ACEIs/ARBs post-TAVR. Patients on ACEIs/ARBs had lower risk of all-cause mortality (RR: 0.74, 95% CI: 0.65-0.86, I2 = 62%, chi-square P < 0.01), cardiovascular mortality (RR: 0.70, 95% CI: 0.56-0.88, I2 = 0%, chi-square P = 0.54), and new-onset atrial fibrillation (RR: 0.71, 95% CI: 0.52-0.96, I2 = 0%, chi-square P = 0.59). Patients on ACEIs/ARBs had a similar risk of myocardial infarction, heart failure, stroke, new permanent pacemaker implantation, acute kidney injury, major bleeding, vascular complications, aortic regurgitation, and mitral regurgitation. ConclusionsWe found that patients receiving ACEIs/ARBs had a lower risk of all-cause mortality, cardiovascular mortality, and new-onset atrial fibrillation. Risk of other outcomes was similar to patients not receiving ACEIs/ARBs. Randomized clinical trials are needed to explore the benefits of ACEIs/ARBs post-TAVR, so that definitive guidelines can be developed.

Angiotensin-converting-enzyme inhibitors and angiotensin receptor blockers for preventing the progression of diabetic kidney disease.

Guidelines suggest that adults with diabetes and kidney disease receive treatment with angiotensin-converting-enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB). This is an update of a Cochrane review published in 2006. We compared the efficacy and safety of ACEi and ARB therapy (either as monotherapy or in combination) on cardiovascular and kidney outcomes in adults with diabetes and kidney disease. We searched the Cochrane Kidney and Transplants Register of Studies to 17 March 2024 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal, and ClinicalTrials.gov. We included studies evaluating ACEi or ARB alone or in combination, compared to each other, placebo or no treatment in people with diabetes and kidney disease. Two authors independently assessed the risk of bias and extracted data. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes and mean difference (MD) or standardised mean difference (SMD) and 95% CI for continuous outcomes. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. One hundred and nine studies (28,341 randomised participants) were eligible for inclusion. Overall, the risk of bias was high. Compared to placebo or no treatment, ACEi may make little or no difference to all-cause death (24 studies, 7413 participants: RR 0.91, 95% CI 0.73 to 1.15; I2 = 23%; low certainty) and with similar withdrawals from treatment (7 studies, 5306 participants: RR 1.03, 95% CI 0.90 to 1.19; I2 = 0%; low certainty). ACEi may prevent kidney failure (8 studies, 6643 participants: RR 0.61, 95% CI 0.39 to 0.94; I2 = 0%; low certainty). Compared to placebo or no treatment, ARB may make little or no difference to all-cause death (11 studies, 4260 participants: RR 0.99, 95% CI 0.85 to 1.16; I2 = 0%; low certainty). ARB have uncertain effects on withdrawal from treatment (3 studies, 721 participants: RR 0.85, 95% CI 0.58 to 1.26; I2 = 2%; low certainty) and cardiovascular death (6 studies, 878 participants: RR 3.36, 95% CI 0.93 to 12.07; low certainty). ARB may prevent kidney failure (3 studies, 3227 participants: RR 0.82, 95% CI 0.72 to 0.94; I2 = 0%; low certainty), doubling of serum creatinine (SCr) (4 studies, 3280 participants: RR 0.84, 95% CI 0.72 to 0.97; I2 = 32%; low certainty), and the progression from microalbuminuria to microalbuminuria (5 studies, 815 participants: RR 0.44, 95% CI 0.23 to 0.85; I2 = 74%; low certainty). Compared to ACEi, ARB had uncertain effects on all-cause death (15 studies, 1739 participants: RR 1.13, 95% CI 0.68 to 1.88; I2 = 0%; low certainty), withdrawal from treatment (6 studies, 612 participants: RR 0.91, 95% CI 0.65 to 1.28; I2 = 0%; low certainty), cardiovascular death (13 studies, 1606 participants: RR 1.15, 95% CI 0.45 to 2.98; I2 = 0%; low certainty), kidney failure (3 studies, 837 participants: RR 0.56, 95% CI 0.29 to 1.07; I2 = 0%; low certainty), and doubling of SCr (2 studies, 767 participants: RR 0.88, 95% CI 0.52 to 1.48; I2 = 0%; low certainty). Compared to ACEi plus ARB, ACEi alone has uncertain effects on all-cause death (6 studies, 1166 participants: RR 1.08, 95% CI 0.49 to 2.40; I2 = 20%; low certainty), withdrawal from treatment (2 studies, 172 participants: RR 0.78, 95% CI 0.33 to 1.86; I2 = 0%; low certainty), cardiovascular death (4 studies, 994 participants: RR 3.02, 95% CI 0.61 to 14.85; low certainty), kidney failure (3 studies, 880 participants: RR 1.36, 95% CI 0.79 to 2.32; I2 = 0%; low certainty), and doubling of SCr (2 studies, 813 participants: RR 1.14, 95% CI 0.70 to 1.85; I2 = 0%; low certainty). Compared to ACEi plus ARB, ARB alone has uncertain effects on all-cause death (7 studies, 2607 participants: RR 1.02, 95% CI 0.76 to 1.37; I2 = 0%; low certainty), withdrawn from treatment (3 studies, 1615 participants: RR 0.81, 95% CI 0.53 to 1.24; I2 = 0%; low certainty), cardiovascular death (4 studies, 992 participants: RR 3.03, 95% CI 0.62 to 14.93; low certainty), kidney failure (4 studies, 2321 participants: RR 1.15, 95% CI 0.67 to 1.95; I2 = 29%; low certainty), and doubling of SCr (3 studies, 2252 participants: RR 1.18, 95% CI 0.85 to 1.64; I2 = 0%; low certainty). Comparative effects of different ACEi or ARB and low-dose versus high-dose ARB were rarely evaluated. No study compared different doses of ACEi. Adverse events of ACEi and ARB were rarely reported. ACEi or ARB may make little or no difference to all-cause and cardiovascular death compared to placebo or no treatment in people with diabetes and kidney disease but may prevent kidney failure. ARB may prevent the doubling of SCr and the progression from microalbuminuria to macroalbuminuria compared with a placebo or no treatment. Despite the international guidelines suggesting not combining ACEi and ARB treatment, the effects of ACEi or ARB monotherapy compared to dual therapy have not been adequately assessed. The limited data availability and the low quality of the included studies prevented the assessment of the benefits and harms of ACEi or ARB in people with diabetes and kidney disease. Low and very low certainty evidence indicates that it is possible that further studies might provide different results.

Comparative Efficacy of Monotherapy of Angiotensin-converting Enzyme Inhibitors Versus Angiotensin Receptor Blockers in Treating Essential Hypertension – A Meta-analysis

Background: Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) are widely used medications for treating essential hypertension, but there is limited research comparing their effectiveness. To address this gap, a recent meta-analysis was conducted to evaluate and compare the efficacy of these two drug classes in decreasing blood pressure (BP) among patients with essential hypertension. Objective: Evaluating of comparative efficacy of ACEIs versus ARBs in reducing BP in essential hypertension. Methods: An extensive literature search for randomized controlled trials (RCTs) following PRISMA guidelines (2020), with inclusion criteria of age ≥18 years, with either gender and diagnosed of essential hypertension and receiving ACEIs or ARBs for at least 4 weeks. Patients with secondary hypertension, malignancy, symptomatic cardiovascular system (CVS) disease, hepatic involvement, and studies with Fimasartan and Allisartan were excluded. For this study, all RCTs that reported changes in mean systolic BP (SBP) and diastolic BP (DBP) before and after administration of the drugs were gathered. Standardized mean difference (SMD) was calculated using RevMan 5.4.1 software. The significance level was set at a P &lt; 0.05. Results: A total of 28 RCTs ( n = 9778) were included in our study. Both groups reduce SBP and DBP from the baseline values. Pooled analyses of studies showed that ARBs were superior to ACEIs with SMD = 0.179 in the random-effect model, 95% confidence interval (CI) (0.0975–0.260), P &lt; 0.001, and in the fixed-effect model, SMD = 0.207, 95% CI (0.167–0.248), P &lt; 0.001 in the mean reduction of SBP. Furthermore, for a mean reduction in DBP, ARBs were superior to ACEIs with SMD = 0.329 in the random-effect model, 95% CI (0.161–0.496), P &lt; 0.001, and in the fixed-effect model, SMD = 0.317, 95% CI (0.276–0.357), P &lt; 0.001. Our study included 28 RCTs with a combined sample size of 9778 participants. Both ACEIs and ARBs were found to effectively reduce SBP and DBP from their baseline values. However, our pooled analysis of the studies revealed that ARBs were more effective than ACEIs in reducing mean SBP, with an SMD of 0.179 in the random-effect model and 0.207 in the fixed-effect model. The 95% CIs for these estimates were (0.0975–0.260) and (0.167–0.248), respectively, with P &lt; 0.001. Similarly, for a mean reduction in DBP, ARBs were found to be superior to ACEIs with a SMD of 0.329 in the random-effect model and 0.317 in the fixed-effect model, with 95% CIs of (0.161–0.496) and (0.276–0.357), respectively, and a P &lt; 0.001. Conclusion: ARBs are more efficacious as compared to ACEIs in essential hypertension.

Effect of pre-transplantation use of angiotensin-converting enzyme inhibitor or angiotensin receptor blocker in kidney transplant recipients-propensity score-matched analysis.

Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers (ACEi/ARBs) can cause acute kidney injury under dehydratation or inhemodynamically unstable conditions. Regarding kidney transplantation (KT), the risk of using ACEi/ARBs before surgery is not well established. Therefore, we evaluated the clinical outcomes to determine the effect of preoperative use of ACEi/ARBs on KT. We retrospectively collected 1187 patients who received living-donor KT between January 2017 and December 2021. We conducted a propensity score-matched analysis between the ACEi/ARB(+) and ACEi/ARB(-) groups and evaluated the effects of ACEi/ARBs on delayed graft function, post-KT renal function, hyperkalemia events, rejection, and graft survival. The ACEi/ARB(+) group showed a similar incidence of delayed graft function as the ACEi/ARB(-) group (1.8% vs. 1.0%, P = 0.362). The risk of delayed graft function was not upregulated in the ACEi/ARB(+) group after propensity score-matching (odds ratio: 0.50, 95% confidence interval (CI) 0.13-2.00). Postoperative creatinine levels and the slope of creatinine levels after KT also were not significantly different between the two groups (creatinine slope from POD#0 to POD#7: -0.73 ± 0.35 vs. -0.75 ± 0.32mg/dL/day, P = 0.464). Hyperkalemia did not occur more often in the ACEi/ARB(+) group than in the ACEi/ARB(-) group during perioperative days. Rejection-free survival (P = 0.920) and graft survival (P = 0.621) were not significantly different between the two groups. In KT, the preoperative use of ACEi/ARBs did not significantly affect clinical outcomes including delayed graft function, postoperative renal function, hyperkalemia events, incidence of rejection, and graft survival rates compared to the patients who did not receive ACEi/ARBs.

Impact of sociodemographic patient factors on prescriber adherence to antihypertensive prescription guidelines: a cross-sectional study using data from The Irish Longitudinal Study on Ageing

Abstract Introduction Uncontrolled hypertension causes significant morbidity and mortality worldwide. Several international prescribing guidelines have been created to address this. However, prescriber adherence to these guidelines may be influenced by sociodemographic patient factors such as socio-economic status, gender and age. Aim To examine the effects of gender and other patient factors, including age, geographical location, educational attainment, duration of disease, socio-economic status, smoking status, and previous history of cardiovascular diseases on prescriber adherence to hypertension prescription guidelines. Achievement of blood pressure goals (&amp;lt;140/90 mmHg) with adherence to prescription guidelines was also assessed. Methods This study is a secondary analysis of cross-sectional data from the first wave (2009-2011) of The Irish Longitudinal Study on Ageing (TILDA), which included 8,175 Irish adults ≥50 years of age. Participants were included in the present study if they reported a previous doctor diagnosis of hypertension. Antihypertensive medication regimens were compared and categorised according to the 2011 National Institute for Health and Clinical Excellence (NICE)[1] prescription guidelines, which included the use of angiotensin converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, calcium channel blockers, and thiazide diuretics in the treatment of hypertension. In this study, the antihypertensive medication regimens of participants were categorised based on age categories (&amp;lt;55, ≥55, and all age groups), and compared to the 2011 NICE Guidelines which differentiate treatment in those ≥55, and &amp;lt;55 years of age. The effects of patient sociodemographic factors on prescriber adherence to the guidelines, and the effects of guideline adherence on blood pressure control, (defined as blood pressure&amp;lt;140/90 mmHg), were determined using multinomial logistic regression models. The mlogit, RRR code in STATA 17 SE was used to report relative risks (RRs). Results A total of 2,992 participants were included, of whom 54.9% were women. The mean age of participants was 65.69 years (±9.23). Male gender, older age and lower socioeconomic status among participants were associated with increased prescriber guideline adherence. Prescribers were less likely to adhere to guidelines in female patients ≥55 years (RR 0.75 [0.62 to 0.91]), and female patients across all age groups (RR 0.80 [0.67 to 0.95]). Better blood pressure control was seen with medication regimens adherent to prescription guidelines with a mean of 140.38 (±18.98)/83.09 (±11.02) mmHg compared to a mean of 141.66 (±19.86)/84.77 (±11.71) mmHg in those non-adherent to guidelines. Conclusion This study highlights the effects of patient gender on prescriber adherence to antihypertensive prescription guidelines. A study strength is the use of a large, nationally representative cohort that used a standardised protocol of data collection within the Irish population. A potential limitation is the inclusion of self-reported data, including doctor diagnosis of hypertension. The results of this study may emphasise a larger issue of the systemic undertreatment of women within healthcare; however, these results should be interpreted in the context of 2011 guidelines, which have since been superseded by 2019 NICE guidelines. Further research may seek to determine possible reasons for such differences in hypertensive care. Reference 1. Linden B. NICE guidance on primary hypertension National Institute for Health and Clinical Excellence (2011) Hypertension: Clinical Management of Primary Hypertension in Adults. NICE Clinical Guideline 127. British journal of cardiac nursing. 2011;6:582-584.

Clinical implications of septic cardiomyopathy: A narrative review.

Sepsis is caused by the body's dysregulated response to infection, which can lead to multiorgan injury and death. Patients with sepsis may develop acute cardiac dysfunction, termed septic cardiomyopathy, which is a global but reversible dysfunction of both sides of the heart. This narrative review discusses the mechanistic changes in the heart during septic cardiomyopathy, its diagnosis, existing treatment options regarding severity and course, and emerging treatment approaches. Although no standardized definition for septic cardiomyopathy exists, it is described as a reversible myocardial dysfunction that typically resolves within 7 to 10 days. Septic cardiomyopathy is often diagnosed based on electrocardiography, cardiac magnetic resonance imaging, biomarkers, and direct invasive and noninvasive measures of cardiac output. Presently, the treatment of septic cardiomyopathy is similar to that of sepsis, primarily focusing on acute interventions. Treatments for cardiomyopathy often include angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and diuretics. However, because of profound hypotension in sepsis, many cardiomyopathy treatments are contraindicated in patients with septic cardiomyopathy. Substantial efforts have been made to study the pathophysiological mechanisms and diagnostic options; however, the lack of a uniform definition for septic cardiomyopathy is challenging for physicians when considering treatments. Another challenge for physicians is that the treatment for septic cardiomyopathy has only focused on acute intervention, whereas the treatment for other cardiomyopathies has been provided on a long-term basis. A better understanding of the underlying mechanisms of septic cardiomyopathy may contribute to the development of a unified definition of the condition and novel treatment options.

Relationship between 2nd-generation angiotensin receptor blockers and the risk of hypotension in COVID-19 patients admitted to hospital.

It has not yet been established whether angiotensin II receptor blockers (ARB), statins, and multiple drugs affect the severity of COVID-19. Therefore, we herein performed an observational study on the effects of 1st- and 2nd-generation ARB, statins, and multiple drugs, on COVID-19 in patients admitted to 15 Japanese medical facilities. The results obtained showed that ARB, statins, and multiple drugs were not associated with the primary outcome (odds ratio: 1.040, 95% confidence interval: 0.688-0.571; 0.696, 0.439-1.103; 1.056, 0.941-1.185, respectively), each component of the primary outcome (in-hospital death, ventilator support, extracorporeal membrane oxygenation support, and admission to the intensive care unit), or the secondary outcomes (oxygen administration, disturbed consciousness, and hypotension, defined as systolic blood pressure ≤90 mmHg). ARB were divided into 1st- and 2nd-generations based on their approval for use (before 2000 and after 2001), with the former consisting of losartan, candesartan, and valsartan, and the latter of telmisartan, olmesartan, irbesartan, and azilsartan. The difference of ARB generation was not associated with the primary outcome (odds ratio with 2nd-generation ARB relative to 1st-generation ARB: 1.257, 95% confidence interval: 0.613-2.574). The odd ratio for a hypotension as one of the secondary outcomes with 2nd-generation ARB was 1.754 (95% confidence interval: 1.745-1.763) relative to 1st-generation ARB. These results suggest that patients taking 2nd-generation ARB may be at a higher risk of hypotension than those taking 1st-generation ARB and also that careful observations are needed. Further studies are continuously needed to support decisions to adjust medications for co-morbidities.

Association of Changes in Vector Length with Changes in Left Ventricular Mass Among Patients on Maintenance Hemodialysis: A Secondary Analysis of the Frequent Hemodialysis Network Daily Trial.

Hypervolemia is thought to be a major contributor to higher left ventricular mass (LVM), a potent predictor for cardiovascular mortality among patients on maintenance hemodialysis. We hypothesized that a decrease in vector length (a bioimpedance proxy of hypervolemia) would be associated with an increase in LVM. Using data from the Frequent Hemodialysis Network Daily Trial (n=160) we used linear regression to assess the association of changes in vector length from baseline to month 12 with changes in magnetic resonance imaging (MRI) measures of LVM and other cardiac parameters. We adjusted models for the randomized group, baseline vector length, age, sex, race, body mass index, vascular access, dialysis vintage, history of hypertension, heart failure, and diabetes, residual kidney function, pre-dialysis systolic blood pressure (BP), ultrafiltration rate, serum-dialysate sodium gradient, hemoglobin, phosphate, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use, erythropoietin dose, and equilibrated Kt/V. The mean age was 50 ±13 years; 35% were female. In the fully adjusted models, a decline in vector length (per 50 Ω/m; i.e., increase in volume) was associated with a 6.8 g (95%CI -0.1, 13.7) and 2.6 g/m2 (95%CI -1.2, 6.3) increase in LVM and LVM index, respectively; and an increase of 15.0 mL (95%CI 7.5, 22.4), 7.3 mL (95%CI 3.0, 12.7), 7.8 mL (95%CI 3.0, 12.7), and -0.9 % (95%CI -3.1, 1.3) in left ventricular (LV) end-diastolic volume (LVEDV), end-systolic volume (LVESV), stroke volume (LVSV), and ejection fraction (LVEF), respectively. The lowest tertile of change in vector length (i.e., greater increase in volume) was associated with greater increases in LVEDV and LVSV, versus the highest tertile. There was no evidence of heterogeneity by randomized group. Change in vector length, a bioimpedance-derived proxy of volume status, was inversely associated with indices of left ventricular mass and volume measured by cardiac MRI in patients randomized to conventional or frequent hemodialysis over 12 months.

Angiotensin Receptor-Neprilysin Inhibitor Suppresses Renin-Angiotensin-Aldosterone System Activation After Cardiac Surgery Using Cardiopulmonary Bypass.

Sacubitril/valsartan, being both a neprilysin inhibitor and angiotensin receptor blocker, exhibits a renin-angiotensin-aldosterone system (RAAS) inhibitory effect. However, no study has investigated the administration of sacubitril/valsartan in patients early after surgery using cardiopulmonary bypass.Methods and Results: This was a prospective observational study of 63 patients who underwent open heart surgery and were treated with sacubitril/valsartan. No serious adverse events occurred. Among the 63 patients, sacubitril/valsartan was discontinued in 13 due to hypotension (n=10), renal dysfunction (n=2), and dizziness (n=1). Atrial natriuretic peptide concentrations increased significantly from Day 3 of treatment (P=0.0142 vs. Postoperative Day 1) and remained high thereafter. In contrast, plasma renin activity was significantly suppressed from Day 3 onwards (P=0.00206 vs. Postoperative Day 1). A decrease in creatinine concentrations and an increase in the estimated glomerular filtration rate were observed on Day 3; this improvement in renal function was not observed in the historical control group, in which patients did not receive sacubitril/valsartan. New postoperative atrial fibrillation was less frequent in the study group compared with the historical control (12.7% vs. 38.0%; P=0.0034). Sacubitril/valsartan administration was safe immediately after open heart surgery in patients without postoperative hypotension. It enhanced serum atrial natriuretic peptide concentrations and suppressed RAAS activation.

[Analysis of long-term prognosis and risk factors in patients with dilated cardiomyopathy].

Objective: To investigate the risk factors and long-term prognosis of major adverse cardiovascular events(MACEs) in patients with dilated cardiomyopathy (DCM). Methods: This study was a single-center retrospective cohort study. Clinical information from 300 patients with DCM hospitalized in Peking Union Medical College Hospital from April 2013 to April 2023 was collected. Based on echocardiography results, the patients were divided into two groups: isolated DCM and DCM with left ventricular non-compaction cardiomyopathy (LVNC). The MACEs, including major heart failure events, severe ventricular arrhythmias, and cardiovascular death, were recorded by outpatient or telephone follow-up. Univariate and multivariate Cox proportional hazard regression models were used to analyze the risk factors affecting the prognosis of patients with DCM. Kaplan-Meier curve and log-rank were used for survival analysis to compare the difference in the incidence of cardiovascular events between the two groups. Results: The included 300 DCM patients were (47.8±16.8) years old, with 197 males (65.7%), of which 237 (79.0%) were isolated DCM and 63 (21.0%) were DCM with LVNC. The follow-up time was 4.0 (1.9, 6.2) years. A total of 142 (47.3%) MACEs occurred, including 117 (39.0%) major heart failure events, 20 (6.7%) severe ventricular arrhythmia events, and 53 (17.7%) cardiovascular death events. Multivariate Cox proportional hazard regression analysis showed that increased left ventricular end-diastolic diameter (HR=1.21, 95%CI: 1.01-1.44, P=0.042), moderate or severe mitral regurgitation (HR=1.71, 95%CI: 1.19-2.47, P=0.004), increased ln (N-terminal pro-B-type natriuretic peptide) (HR=1.30, 95%CI: 1.10-1.54, P=0.002) were independent risk factors for dverse cardiovascular events in DCM patients, and angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB)/angiotensin receptor neprilysin inhibitor (ARNI) treatment (HR=0.45, 95%CI: 0.26-0.78, P=0.004) was independent protective factor. Kaplan-Meier survival analysis found no significant difference in the risk of MACEs between isolated DCM and DCM with LVNC (P=0.22). Similarly, there were no significant differences in the incidence of major heart failure, severe ventricular arrhythmia, and cardiovascular death between the two groups (all P>0.05). Conclusion: An increase in left ventricular end-diastolic diameter, moderate or severe mitral regurgitation, elevated N-terminal pro-B-type natriuretic peptide, and non use of ACEI/ARB/ARNI are independent predictors of cardiovascular events in DCM patients. There was no significant risk of MACEs in patients with isolated DCM and DCM with LVNC, and suggested that LVNC may be a unique phenotype and should be accurately managed in combination with genetic background.

Correlation between Urinary Angiotensinogen (AGT) and Albuminuria in Chronic Kidney Disease (CKD)

Chronic kidney disease (CKD) is a global health concern associated with significant morbidity and mortality. Albuminuria, a hallmark of kidney damage, is a strong predictor of CKD progression and adverse outcomes. Recent research has focused on understanding the correlation between urinary angiotensinogen (AGT) levels, a component of the renin-angiotensin system (RAS), and albuminuria in CKD patients. This review article synthesizes evidence from various studies exploring this correlation and elucidates its mechanistic insights and clinical implications. Clinical studies consistently demonstrate a positive correlation between urinary AGT levels and albuminuria in CKD patients. Elevated urinary AGT levels are associated with increased albuminuria, independent of traditional risk factors, suggesting a potential role for AGT in the pathogenesis of kidney damage and proteinuria in CKD. Mechanistic insights suggest that increased intrarenal RAS activity may lead to enhanced AGT production and secretion, contributing to glomerular hypertension, inflammation, and fibrosis, ultimately promoting albuminuria and CKD progression. The clinical implications of this correlation are profound. Elevated urinary AGT levels may serve as a non-invasive biomarker for assessing intrarenal RAS activity and predicting CKD progression and adverse outcomes. Furthermore, interventions targeting the RAS pathway, such as angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs), may help reduce urinary AGT levels and mitigate albuminuria, offering promising therapeutic opportunities for improving patient outcomes in CKD. In conclusion, the correlation between urinary AGT and albuminuria in CKD represents a complex interplay between renal physiology, RAS activation, and kidney damage. By elucidating this correlation, we gain valuable insights into the pathogenesis of CKD and identify urinary AGT as a potential biomarker and therapeutic target for personalized CKD management. Further research is warranted to validate these findings, explore the clinical utility of urinary AGT measurement, and develop targeted interventions aimed at mitigating albuminuria and slowing CKD progression. Through continued investigation, we can strive to improve outcomes and quality of life for patients living with CKD.

A case report and literature review of IgA nephropathy presenting as nephrotic syndrome in polycythemia vera.

A 66-year-old non-smoker presented with a 2-week history of new-onset pedal oedema and gross haematuria. On evaluation, he was found to be hypertensive and oedematous with a haemoglobin of 19.1g/dl, platelet count of 546,000/mm3, and creatinine of 2.6mg/dl. Urine examination revealed abundant RBCs with 3+ albumin on three separate occasions. His 24-h urine protein level was 3830mg/day, with a serum cholesterol level of 303mg/dl. Secondary erythrocytosis and thrombocytosis tests were negative. Bone marrow examination revealed hypercellularity, erythroid hyperplasia, tight clusters of large megakaryocytes, and megakaryocytic hyperplasia suggestive of polycythemia vera. PCR analysis revealed a JAK2V617 F (exon 14) mutation. In view of nephrotic syndrome, azotemia, and microscopic haematuria, a renal biopsy was performed, which revealed features of IgA nephropathy with advanced interstitial fibrosis and tubular atrophy. He was started on angiotensin receptor blockers with hydroxy urea as a part of treatment. This case report highlights the association of glomerular disease with polycythaemia vera and the need of prompt renal biopsy for diagnosis and management.