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This study aimed to evaluate the association between sacubitril/valsartan and dementia-related adverse events (AEs) in geographical subpopulations using subgroup disproportionality analysis. Cases from the FDA adverse event reporting system involving patients aged 60 or older with sacubitril/valsartan or angiotensin receptor blockers (ARBs) were analyzed. The adjusted reporting odds ratios (RORs) for dementia-related AEs were calculated for each continent. A total of 61,518 AEs associated with sacubitril/valsartan or ARBs were identified. Among these, 1441 were dementia-related AEs. In Asia, Europe, and Africa, the reporting risk of dementia-related AEs associated with sacubitril/valsartan was lower compared to ARBs (adjusted ROR, 0.57 [95% CI 0.31–1.01]; adjusted ROR, 0.89 [95% CI 0.69–1.14]; adjusted ROR, 0.40 [95% CI 0.27–0.61], respectively). In Latin America and Oceania, the reporting risk of dementia-related AEs associated with sacubitril/valsartan was similar to that associated with ARBs (adjusted ROR, 1.04 [95% CI 0.75–1.44]; adjusted ROR, 1.02 [95% CI 0.31–3.37], respectively). On the contrary, in North America, the reporting risk associated with sacubitril/valsartan was higher compared to ARBs (adjusted ROR, 1.29 [95% CI 1.10–1.53]). Although the ROR value did not meet the criteria for signal detection, the significantly greater than 1 ROR observed in North America suggests that caution may be warranted regarding potential dementia-related adverse events associated with sacubitril/valsartan. [ABSTRACT FROM AUTHOR]

Blockade of Angiotensin type 1 receptor (AT1R) has potential therapeutic utility in the treatment of numerous detrimental consequences of epileptogenesis, including oxidative stress, neuroinflammation, and blood–brain barrier (BBB) dysfunction. We have recently shown that many of these pathological processes play a critical role in seizure onset and propagation in the Scn8a-N1768D mouse model. Here we investigate the efficacy and potential mechanism(s) of action of candesartan (CND), an FDA-approved angiotensin receptor blocker (ARB) indicated for hypertension, in improving outcomes in this model of pediatric epilepsy. We compared length of lifespan, seizure frequency, and BBB permeability in juvenile (D/D) and adult (D/+) mice treated with CND at times after seizure onset. We performed RNAseq on hippocampal tissue to quantify differences in genome-wide patterns of transcript abundance and inferred beneficial and detrimental effects of canonical pathways identified by enrichment methods in untreated and treated mice. Our results demonstrate that treatment with CND gives rise to increased survival, longer periods of seizure freedom, and diminished BBB permeability. CND treatment also partially reversed or ‘normalized’ disease-induced genome-wide gene expression profiles associated with inhibition of NF-κB, TNFα, IL-6, and TGF-β signaling in juvenile and adult mice. Pathway analyses reveal that efficacy of CND is due to its known dual mechanism of action as both an AT1R antagonist and a PPARγ agonist. The robust effectiveness of CND across ages, sexes and mouse strains is a positive indication for its translation to humans and its suitability of use for clinical trials in children with SCN8A epilepsy [ABSTRACT FROM AUTHOR]

This article discusses medication management during sick days for patients with and without impaired renal function. The study found that patients with impaired renal function were often using high-risk drugs and were at risk for acute renal failure during sick days. However, there were no differences in medication management between patients with and without impaired renal function. The study suggests that healthcare professionals should improve information provision and support patients in their drug management during sick days. It also emphasizes the importance of involving informal caregivers in the process. [Extracted from the article]

Summary: Background: Withholding or continuing angiotensin‐converting enzyme inhibitors or angiotensin 2 receptor blockers peri‐operatively in non‐cardiac surgery remains controversial as they may result in intra‐operative hypotension and postoperative organ damage. Methods: We included patients prescribed angiotensin‐converting enzyme inhibitors or angiotensin 2 receptor blockers who underwent surgical procedures > 1 h duration under general or spinal anaesthesia from January 2012 to June 2022 in a single centre. We categorised patients by whether these drugs were withheld for 24 h before surgery. We evaluated the association of withholding these drugs before non‐cardiac surgery with creatinine concentrations that increased ≥ 26.4 μmol.l‐1 in the first 48 postoperative hours (acute kidney injury). We also analysed changes in creatinine concentrations and estimated glomerular filtration rates. Results: Angiotensin‐converting enzyme inhibitors or angiotensin 2 receptor blockers were withheld in 24,285 of 32,933 (74%) patients and continued in 8648 (26%) patients. We used propensity scores for drug discontinuation to match 8631 patient pairs who did or did not continue these drugs: acute kidney injury was recorded for 1791 (21%) patients who continued these drugs vs. 1587 (18%) who did not (OR (95%CI) 1.16 (1.08–1.25), p < 0.001). Intra‐operative hypotension was recorded for 3892 (45%) patients who continued drugs vs. 3373 (39%) patients who did not (OR (95%CI) 1.28 (1.21–1.36), p < 0.001). Continuing drugs was independently associated with a mean increase in creatinine of 2.2 μmol.l‐1 (p < 0.001) and a mean decrease in estimated glomerular filtration rate of 1.4 ml.min.1.73 m‐2 (p < 0.001). Conclusions: Continuing angiotensin‐converting enzyme inhibitors or angiotensin 2 receptor blockers 24 h before non‐cardiac surgery was associated with intra‐operative hypotension and postoperative acute kidney injury. [ABSTRACT FROM AUTHOR]

Gynecological cancers constitute a significant health burden for females worldwide, with cervical, endometrial and ovarian cancer being the most common types. The renin-angiotensin-aldosterone (RAA) system regulates blood pressure and is involved in various diseases, such as hypertension and heart failure. However, several studies have found that the angiotensin-1 receptor (AT1R) pathway is activated in various types of cancers, including breast, pancreatic and colorectal cancers. The AT1R receptor, in particular, has been shown to induce proliferation, neovascularization and fibrosis; therefore, its activation may induce cancer progression. Several epidemiological studies have found an association between angiotensin-converting enzyme inhibitors and angiotensin receptor blockers (ARBs) with reduced cancer incidence; however, others have reported unclear or even deleterious associations between ARB use and cancers. These conflicting results necessitate the further exploration of the influence of the RAA system in the development of gynecological cancers. Several new factors in the RAA system have been identified, including angiotensin-(1-7) and angiotensin-(1-9), which have been shown to play a crucial role in preventing cell proliferation and, possibly, cancer progression. The present review discusses the association between the RAA system and gynecological cancers, specifically endometrial, ovarian and cervical cancers. [ABSTRACT FROM AUTHOR]

Context Patients with nonfunctioning adrenal adenomas (NFA) and mild autonomous cortisol secretion (MACS) demonstrate an increased risk of chronic kidney disease (CKD); however, factors associated with CKD are unknown. Objective We aimed to identify the factors associated with CKD and assess the effect of adrenalectomy on kidney function in patients with NFA or MACS. Methods A single-center cohort study of patients with NFA and MACS, 1999 to 2020, was conducted. MACS was diagnosed based on post dexamethasone suppression test (DST) cortisol greater than or equal to 1.8 mcg/dL. Age, sex, dysglycemia, hypertension, therapy with statin, angiotensin-converting enzyme inhibitor, or angiotensin II receptor blocker were included in the multivariable analysis. Outcomes included estimated glomerular filtration rate (eGFR) at the time of diagnosis with MACS or NFA and postadrenalectomy delta eGFR. Results Of 972 patients, 429 (44%) had MACS and 543 (56%) had NFA. At the time of diagnosis, patients with MACS had lower eGFR (median 79.6 vs 83.8 mL/min/1.73 m2; P <.001) than patients with NFA. In a multivariable analysis, factors associated with lower eGFR were older age, hypertension, and higher DST. In 204 patients (MACS: 155, 76% and NFA: 49, 24%) treated with adrenalectomy, postadrenalectomy eGFR improved in both groups starting at 18 months up to 3.5 years of follow-up. Factors associated with increased eGFR were younger age, lower preadrenalectomy eGFR, and longer follow-up period. Conclusion DST cortisol is an independent risk factor for lower eGFR in patients with adrenal adenomas. Patients with both MACS and NFA demonstrate an increase in eGFR post adrenalectomy, especially younger patients with lower eGFR pre adrenalectomy. [ABSTRACT FROM AUTHOR]

Scandinavian electronic health-care registers provide a unique setting to investigate potential unidentified side effects of drugs. We analysed the association between prescription drugs dispensed in Norway and Sweden and the short-term risk of developing pulmonary embolism. A total of 12,104 pulmonary embolism cases were identified from patient- and cause-of-death registries in Norway (2004–2014) and 36,088 in Sweden (2005–2014). A case-crossover design was used to compare individual drugs dispensed 1–30 days before the date of pulmonary embolism diagnosis with dispensation in a 61–90 day time-window, while controlling for the receipt of other drugs. A BOLASSO approach was used to select drugs that were associated with short-term risk of pulmonary embolism. Thirty-eight drugs were associated with pulmonary embolism in the combined analysis of the Norwegian and Swedish data. Drugs associated with increased risk of pulmonary embolism included certain proton-pump inhibitors, antibiotics, antithrombotics, vasodilators, furosemide, anti-varicose medications, corticosteroids, immunostimulants (pegfilgrastim), opioids, analgesics, anxiolytics, antidepressants, antiprotozoals, and drugs for cough and colds. Mineral supplements, hydrochlorothiazide and potassium-sparing agents, beta-blockers, angiotensin 2 receptor blockers, statins, and methotrexate were associated with lower risk. Most associations persisted, and several additional drugs were associated, with pulmonary embolism when using a longer time window of 90 days instead of 30 days. These results provide exploratory, pharmacopeia-wide evidence of medications that may increase or decrease the risk of pulmonary embolism. Some of these findings were expected based on the drugs' indications, while others are novel and require further study as potentially modifiable precipitants of pulmonary embolism. [ABSTRACT FROM AUTHOR]

Background: Nearly half of patients with heart failure (HF) have preserved ejection fraction (EF) and the mortality and morbidity of patients with HF with preserved EF (HFpEF) are high. Patients with HFpEF are often elderly and their primary chronic symptom is severe exercise intolerance. Due to the frequent coexistence of hypertension in HFpEF patients, the use of anti-hypertensive medications is common in their treatment. While many cohort studies and several randomized controlled trials (RCTs) have examined the effectiveness of various anti-hypertensive drugs such as beta-blockers and renin-angiotensin system inhibitors in HFpEF, the role of calcium channel blockers (CCBs) remains uncertain. Despite several RCTs and cohort studies exploring the effects of CCBs on prognosis and exercise capacity in HFpEF patients, the findings have been inconsistent, likely due to limited statistical power and/or variations in study design. Therefore, our aim is to conduct a systematic review and meta-analysis of studies on the effects of CCBs in these patients. Methods: This meta-analysis will include RCTs and cohort studies on the effect of CCBs in HFpEF patients. Information of studies will be collected from PubMed, Web of Science, and Scopus. The primary outcome of interest will be prognosis. The secondary outcome of interest will be exercise capacity. Discussion: Synthesizing our meta-analytical results with expert consensus could contribute to the formulation of updated clinical guidelines. Our systematic review and meta-analysis will provide directions for future research on the use of CCBs in HFpEF patients. Systematic review registration: INPLASY202430097. [ABSTRACT FROM AUTHOR]

Aims Methods and results Conclusion Heart failure (HF) with preserved ejection fraction (HFpEF) is characterized by growing incidence and poor outcomes. A large majority of HFpEF patients are cared by non‐cardiologists. The availability of sodium–glucose cotransporter 2 inhibitors (SGLT2i) as recommended therapy raises the importance of prompt and accurate identification and treatment of HFpEF across diverse healthcare settings. We evaluated HFpEF management across specialties through a survey targeting cardiologists, HF specialists, and non‐cardiologists.An independent web‐based survey was distributed globally between May and July 2023. We performed a post‐hoc analysis, comparing cardiologists, HF specialists, and non‐cardiologists. A total of 1460 physicians (61% male, median age 41[34–49]) from 95 countries completed the survey; 20% were HF specialists, 65% cardiologists, and 15% non‐cardiologists. Compared with HF specialists, non‐cardiologists and cardiologists were less likely to use natriuretic peptides (p = 0.003) and HFpEF scores (p = 0.004) for diagnosis, and were also less likely to have access to or consider specific echocardiographic parameters (p < 0.001) for identifying HFpEF. Diastolic stress tests were used in less than 30% of the cases, regardless of the specialty (p = 1.12). Multidrug treatment strategies were similar across different specialties. While SGLT2i and diuretics were the preferred drugs, angiotensin receptor blockers and angiotensin receptor–neprilysin inhibitors were the least frequently prescribed in all three groups. However, when constrained to choose one drug, the proportion of physicians favoring SGLT2i varied significantly among specialties (66% HF specialists, 52% cardiologists, 51% non‐cardiologists). Additionally, 10% of non‐cardiologists and 8% of cardiologists considered beta blocker the drug of choice for HFpEF.Significant differences among specialty groups were observed in HFpEF management, particularly in the diagnostic work‐up. Our results highlight a substantial risk of underdiagnosis and undertreatment of HFpEF patients, especially among non‐HF specialists. [ABSTRACT FROM AUTHOR]

Background: Depression ranks as a leading contributor to the global disease burden. The potential causal relationship between the use of antihypertensivemedications and depression has garnered significant interest.Despite extensive investigation, the nature of this relationship remains a subject of ongoing debate. Therefore, this study aims to evaluate the influence of antihypertensivemedications on depression by conducting a Mendelian randomization study focused on drug targets. Method: We focused on the targets of five antihypertensive drug categories: ACE Inhibitors (ACEIs), Angiotensin II Receptor Antagonists (ARBs), Calcium Channel Blockers (CCBs), Beta-Blockers (BBs), and Thiazide Diuretics (TDs). We collected single-nucleotide polymorphisms (SNPs) associated with these drug targets from genome-wide association study (GWAS) statistics, using them as proxies for the drugs. Subsequently, we conducted a Mendelian randomization (MR) analysis targeting these drugs to explore their potential impact on depression. Results: Our findings revealed that genetic proxies for Beta-Blockers (BBs) were associated with an elevated risk of depression (OR [95%CI] = 1.027 [1.013, 1.040], p < 0.001). Similarly, genetic proxies for Calcium Channel Blockers (CCBs) were linked to an increased risk of depression (OR [95%CI] = 1.030 [1.009, 1.051], p = 0.006). No significant associations were identified between the genetic markers of other antihypertensive medications and depression risk. Conclusion: The study suggests that genetic proxies associated with Beta- Blockers (BBs) and Calcium Channel Blockers (CCBs) could potentially elevate the risk of depression among patients. These findings underscore the importance of considering genetic predispositions when prescribing these medications, offering a strategic approach to preventing depression in susceptible individuals. [ABSTRACT FROM AUTHOR]

Angiotensin receptor blockade has been linked to aspects of aversive learning and memory formation and to the prevention of posttraumatic stress disorder symptom development. We investigated the influence of the angiotensin receptor blocker losartan on aversive Pavlovian conditioning using a probabilistic learning paradigm. In a double-blind, randomized, placebo-controlled design, we tested 45 (18 female) healthy volunteers during a baseline session, after application of losartan or placebo (drug session), and during a follow-up session. During each session, participants engaged in a task in which they had to predict the probability of an electrical stimulation on every trial while the true shock contingencies switched repeatedly between phases of high and low shock threat. Computational reinforcement learning models were used to investigate learning dynamics. Acute administration of losartan significantly reduced participants' adjustment during both low-to-high and high-to-low threat changes. This was driven by reduced aversive learning rates in the losartan group during the drug session compared with baseline. The 50-mg drug dose did not induce reduction of blood pressure or change in reaction times, ruling out a general reduction in attention and engagement. Decreased adjustment of aversive expectations was maintained at a follow-up session 24 hours later. This study shows that losartan acutely reduces Pavlovian learning in aversive environments, thereby highlighting a potential role of the renin-angiotensin system in anxiety development. [ABSTRACT FROM AUTHOR]

Background: Hepatitis B virus (HBV) infection is a common cause of liver-related morbidity and mortality. Evidence suggests that angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) decrease liver fibrosis, an intermediate step between liver injury and hepatocellular carcinoma (HCC). Our aim was to investigate the association between the use of ACEIs and ARBs on incident HCC and liver-related mortality among patients with HBV infection. Methods: We conducted a population-based study on a new-user cohort of patients seen at 24 hospitals across China. We included adult patients with HBV infection who started ACEIs or ARBs (ACEIs/ARBs), or calcium channel blockers or thiazide diuretics (CCBs/THZs) from January 2012 to December 2022. The primary outcome was incident HCC; secondary outcomes were liver-related mortality and new-onset cirrhosis. We used propensity score matching and Cox proportional hazards regression to estimate the hazard ratio (HR) and 95% confidence intervals (CIs) of study outcomes. Results: Among 32 692 eligible patients (median age 58 [interquartile range (IQR) 48–68] yr, and 18 804 male [57.5%]), we matched 9946 pairs of patients starting ACEIs/ARBs or CCBs/THZs. During a mean follow-up of 2.3 years, the incidence rate of HCC per 1000 person-years was 4.11 and 5.94 among patients who started ACEIs/ARBs and CCBs/THZs, respectively, in the matched cohort. Use of ACEIs/ARBs was associated with lower risks of incident HCC (HR 0.66, 95% CI 0.50–0.86), liver-related mortality (HR 0.77, 95% CI 0.64–0.93), and new-onset cirrhosis (HR 0.81, 95% CI 0.70–0.94). Interpretation: In this cohort of patients with HBV infection, new users of ACEIs/ARBs had a lower risk of incident HCC, liver-related mortality, and new-onset cirrhosis than new users of CCBs/THZs. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusion Sodium–glucose cotransporter 2 inhibitors (SGLT2is), used as a glucose‐lowering therapy in people with type 2 diabetes (T2D), have significant cardiorenal benefits, reducing hospitalization for heart failure (HF) and cardiovascular mortality in patients with and without T2D. Recent clinical trial evidence suggests their potential utility in preventing incident T2D among the high‐risk HF populations. Therefore, we aimed to assess whether this finding was reproducible in a real‐world setting.We performed a retrospective cohort analysis of 484 643 patients with HF, without baseline diabetes, prescribed either angiotensin‐converting enzyme inhibitors or angiotensin II receptor blockers with/without SGLT2is (treatment, n = 42 018; reference, n = 442 625) across 95 global health care organizations, using a large real‐world ecosystem. Propensity score matching balanced arms 1:1 for confounders (n = 39 168 each arm). Subgroup analysis further evaluated the impact on patients with prediabetes and the efficacy of dapagliflozin/empagliflozin, specifically, on incident T2D and secondary outcomes, including all‐cause mortality, acute pulmonary oedema and hospitalization.Treatment with SGLT2is significantly reduced incident T2D {hazard ratio (HR) 0.71 [95% confidence interval (CI) 0.63, 0.75]} in patients with HF. The analysis of patients with prediabetes found that SGLT2is further reduced incident T2D [HR 0.62 (95% CI 0.45, 0.80)]. The magnitude of reduction in incident T2D was higher in patients prescribed dapagliflozin [HR 0.47 (95% CI 0.39, 0.56)] versus empagliflozin [HR 0.81 (95% CI 0.70, 0.93)].Treatment with SGLT2is in patients with HF was associated with a reduced risk of incident T2D, most strikingly in people with prediabetes. [ABSTRACT FROM AUTHOR]

AbstractIntroductionMethodsResultsDiscussionConclusionsThe Extracorporeal Treatments in Poisoning (EXTRIP) workgroup suggests hemodialysis in severe lithium poisoning if specific criteria are met. One criterion is if the expected time to obtain a lithium concentration <1.0 mEq/L with optimal management is >36 h. There are a lack of data regarding which patient characteristics are associated with the rate at which patients achieve a lithium concentration <1.0 mEq/L.We conducted a retrospective chart review analyzing hospital electronic medical records. Inclusion criteria consisted of a lithium concentration >1.2 mEq/L during hospitalization. We excluded patients who received extracorporeal treatment before 36 h elapsed from time of initial lithium concentration >1.2 mEq/L. The primary analysis consisted of a Cox regression and a secondary analysis evaluated the nomogram method described by Buckley and colleagues for predicting prolonged supratherapeutic lithium concentration.One hundred and one patients were included in the study. The median time to reach a lithium concentration <1.0 mEq/L was 42.5 h (IQR: 33.8–51.1). Older patients, patients taking a thiazide, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, patients with a higher initial lithium concentration, and patients with higher sodium concentrations achieved a lithium concentration <1 mEq/L at a slower rate. For the nomogram analysis, sensitivity (61.5%) and specificity (54.5%) were moderate, the positive predictive value (16.7%) was poor, and the negative predictive value (90.6%) was excellent.The results from our primary analysis suggest that identifying higher serum sodium concentration and use of certain antihypertensives that decrease glomerular filtration rate as predictors of an increased time to reach a therapeutic lithium concentration may help identify patients who meet the Extracorporeal Treatments in Poisoning criteria for hemodialysis. The nomogram method performed similarly to prior validation studies.In this retrospective chart review of patients with supratherapeutic lithium concentrations, we identified several risk factors for prolonged supratherapeutic lithium concentrations. [ABSTRACT FROM AUTHOR]

Background: The management of non-communicable diseases (NCDs) has benefited from telehealth services. As these services which include teleconsultation services and e-prescriptions are relatively new in Malaysia, the data generated provide an unprecedented opportunity to study medication use patterns for the management of NCDs in the country. We analyze e-prescriptions from a local telehealth service to identify medication use patterns and potential areas to optimize medication use in relation to clinical practice guidelines. Methods: A cross sectional observational study was conducted by retrieving e-prescription records retrospectively from a telehealth service. 739,482 records from January 2019 to December 2021 were extracted using a designated data collection form. Data cleaning, standardization and data analysis were performed using Python version 3.11. The diagnoses were classified according to the International Classification of Disease 10 (ICD-10), while medications were classified using the Anatomical Therapeutic Chemical (ATC) system. Diagnoses, frequency of use for medication classes and individual medications were analyzed and compared to clinical practice guidelines. Results: The top five NCD diagnoses utilized by the service were hypertension (37.7%), diabetes mellitus (25.1%), ischemic heart disease (24.3%), asthma (14.4%), and dyslipidemia (11.7%). Medications were prescribed mostly in accordance with guideline recommendations. However, angiotensin receptor blockers (ARBs) were significantly more frequently prescribed compared to angiotensin converting enzyme inhibitors (ACEIs). Several medication classes appeared underutilized, including ACEIs in hypertensive patients with diabetes or ischemic heart disease, sodium glucose cotransporter 2 inhibitors in diabetic patients with ischemic heart disease, and metformin in patients with diabetes. Conclusions: Telehealth services are currently being utilized for the management of NCDs. Medication use for the management of NCDs through these services are mostly in accordance with guideline recommendations, but there exist areas that would warrant further investigation to ensure optimal clinical and economic outcomes are achieved. [ABSTRACT FROM AUTHOR]

Background: The fundamental role of the renin–angiotensin–aldosterone system in the pathophysiology of chronic kidney disease, congestive heart failure, hypertension and proteinuria is well established in pre‐clinical and clinical studies. Mineralocorticoid receptor antagonists are among the primary options for renin–angiotensin–aldosterone system blockage, along with angiotensin‐converting enzyme inhibitors and angiotensin receptor blockers. Methods: In this narrative review, we aim to evaluate the efficiency and safety of mineralocorticoid receptor antagonists in kidney transplant recipients, including the potential underlying pathophysiology. Results: The efficiency and safety of mineralocorticoid receptor antagonists in managing chronic kidney disease and proteinuria, either non‐nephrotic or nephrotic range, have been demonstrated among nontransplanted patients, though studies investigating the role of mineralocorticoid receptor antagonists among kidney transplant recipients are scarce. Nevertheless, promising results have been reported in pre‐clinical and clinical studies among kidney transplant recipients regarding the role of mineralocorticoid receptor antagonists in terms of ischaemia–reperfusion injury, proteinuria, or calcineurin inhibitor‐mediated nephrotoxicity without considerable adverse events such as hypotension, hyperkalaemia or worsening renal functions. Conclusion: Even though initial results regarding the role of mineralocorticoid receptor antagonist therapy for kidney transplant recipients are promising, there is clear need for large‐scale randomized clinical trials with long‐term follow‐up data. [ABSTRACT FROM AUTHOR]

This article discusses the potential differences in optimal doses of heart failure medications between women and men. It highlights the biological factors that may contribute to these differences, such as variations in body composition, drug absorption, metabolism, and elimination. The article presents findings from observational studies that suggest women may require lower doses than men to achieve significant clinical benefits, particularly for certain medications. However, it emphasizes the need for further research and the inclusion of sex-specific data on adverse effects to establish truly personalized and effective treatment guidelines for both women and men with heart failure. The article also addresses the existing disparities in the treatment of women with heart failure and calls for more representative inclusion of women in clinical trials. [Extracted from the article]

Aims: Although recent randomized clinical trials have demonstrated the advantages of heart failure (HF) therapy in both frail and not frail patients, there is insufficient information on the use of HF therapy based on frailty status in a real‐world setting. The aim was to examine how frailty status in HF patients associates with use of HF therapy and with clinical outcomes. Methods and results: Patients with new‐onset HF between 2014 and 2021 were identified using the nationwide Danish registers. Patients across the entire range of ejection fraction were included. The associations between frailty status (using the Hospital Frailty Risk Score) and use of HF therapy and clinical outcomes (all‐cause mortality, HF hospitalization, and non‐HF hospitalization) were evaluated using multivariable‐adjusted Cox models adjusting for age, sex, diagnostic setting, calendar year, comorbidities, pharmacotherapy, and socioeconomic status. Of 35 999 participants (mean age 69.1 years), 68% were not frail, 26% were moderately frail, and 6% were severely frail. The use of HF therapy was significantly lower in frailer patients. The hazard ratio (HR) for angiotensin‐converting enzyme inhibitor/angiotensin receptor blocker initiation was 0.74 (95% confidence interval 0.70–0.77) and 0.48 (0.43–0.53) for moderate frailty and severe frailty, respectively. For beta‐blockers, the corresponding HRs were 0.74 (0.71–0.78) and 0.51 (0.46–0.56), respectively, and for mineralocorticoid receptor antagonists, 0.83 (0.80–0.87) and 0.58 (0.53–0.64), respectively. The prevalence of death and non‐HF hospitalization increased with frailty status. The HR for death was 1.55 (1.47–1.63) and 2.32 (2.16–2.49) for moderate and severe frailty, respectively, and the HR for non‐HF hospitalization was 1.37 (1.32–1.41) and 1.82 (1.72–1.92), respectively. The association between frailty status and HF hospitalization was not significant (HR 1.08 [1.02–1.14] and 1.08 [0.97–1.20], respectively). Conclusion: In real‐world HF patients, frailty was associated with lower HF therapy use and with a higher incidence of clinical outcomes including mortality and non‐HF hospitalization. [ABSTRACT FROM AUTHOR]

Dysbiosis of the gut microbiota has been implicated in hypertension, and drug–host–microbiome interactions have drawn considerable attention. However, the influence of angiotensin receptor blocker (ARB)‐shaped gut microbiota on the host is not fully understood. In this work, we assessed the alterations of blood pressure (BP), vasculatures, and intestines following ARB‐modified gut microbiome treatment and evaluated the changes in the intestinal transcriptome and serum metabolome in hypertensive rats. Hypertensive patients with well‐controlled BP under ARB therapy were recruited as human donors, spontaneously hypertensive rats (SHRs) receiving normal saline or valsartan were considered animal donors, and SHRs were regarded as recipients. Histological and immunofluorescence staining was used to assess the aorta and small intestine, and 16S rRNA amplicon sequencing was performed to examine gut bacteria. Transcriptome and metabonomic analyses were conducted to determine the intestinal transcriptome and serum metabolome, respectively. Notably, ARB‐modified fecal microbiota transplantation (FMT), results in marked decreases in systolic BP levels, collagen deposition and reactive oxygen species accumulation in the vasculature, and alleviated intestinal structure impairments in SHRs. These changes were linked with the reconstruction of the gut microbiota in SHR recipients post‐FMT, especially with a decreased abundance of Lactobacillus, Aggregatibacter, and Desulfovibrio. Moreover, ARB‐treated microbes contributed to increased intestinal Ciart, Per1, Per2, Per3, and Cipc gene levels and decreased Nfil3 and Arntl expression were detected in response to ARB‐treated microbes. More importantly, circulating metabolites were dramatically reduced in ARB‐FMT rats, including 6beta‐Hydroxytestosterone and Thromboxane B2. In conclusion, ARB‐modified gut microbiota exerts protective roles in vascular remodeling and injury, metabolic abnormality and intestinal dysfunctions, suggesting a pivotal role in mitigating hypertension and providing insights into the cross‐talk between antihypertensive medicines and the gut microbiome. Highlights: Angiotensin receptor blocker (ARB)‐modified gut microbiota leads to reduced systolic blood pressure levels and exerts protective roles in spontaneously hypertensive rats (SHRs).ARB‐modified fecal microbiota transplantation (FMT) contributes to the reconstruction of the gut microbiota, serum metabolome, and intestinal transcriptome SHRs.Treatment with ARB‐modified FMT results in marked decreases in collagen deposition and reactive oxygen species accumulation in the vasculature as well as alleviated vascular and intestinal structural impairments in hypertensive rats. [ABSTRACT FROM AUTHOR]

• European guidelines recommend initial dual combination for most hypertensive patients. • Dual combination of an ACEi or ARB, with a CCB or a thiazide is recommended. • If BP not controlled, next step is the combination of these three drug classes. • Single pill combination of drugs is preferred to improve adherence and persistence. • Monotherapy should be restricted to a small group of hypertensive patients. Elevated blood pressure (BP) is the largest contributor to the incident cardiovascular disease worldwide. Despite explicit guideline recommendations for the diagnosis and management of hypertension, a large proportion of patients remain undiagnosed, untreated, or treated but uncontrolled. Inadequate BP control is associated with many complex factors including patient preference, physician's inertia, health systems disparities, and poor adherence to prescribed antihypertensive drug treatment. The primary driver for reduced cardiovascular morbidity and mortality is lowering of BP "per se" and not class effects of specific pharmacotherapies. The recent ESH guidelines recommend the use of four major classes of drugs including renin‐angiotensin‐aldosterone system (RAS) blockers (angiotensin receptor blockers (ARB) or angiotensin‐converting enzyme inhibitors (ACEi)), calcium channel blockers (CCB), thiazide and thiazide‐like diuretics, and betablockers. Initiation of treatment for hypertension with a two-drug regimen, preferably in a single pill combination (SPC), is recommended for most patients. Preferred combinations should comprise a RAS blocker (either an ACEi or an ARB) with a CCB or thiazide/thiazide-like diuretic. These strategies are supported by robust evidence that combination therapy produces greater BP reductions than monotherapy, reduces side effects of the individual components, improves therapeutic adherence and long-term persistence on treatment, and permits achievement of earlier BP control. [ABSTRACT FROM AUTHOR]

This article provides a list of references to scientific articles on various topics related to personalized and precision medicine. The references cover subjects such as cardiovascular risk assessment, biomarkers for cancer, machine learning in healthcare, circadian rhythms, and personalized medicine. These articles can serve as a valuable resource for library patrons conducting research on these specific topics. [Extracted from the article]

Introduction: The aim of this study was to investigate the role of sacubitril/valsartan in managing hypertension and cardiac remodeling in patients undergoing hemodialysis. Methods: Hemodialysis patients with stable blood pressure control were enrolled in the study. Sacubitril/valsartan was prescribed to replace previously used angiotensin-converting enzyme inhibitor/angiotensin receptor blocker or other antihypertensive drugs. During a 6-month follow-up period, pre-dialysis blood pressure, routine biochemical markers, and N-terminal pro-brain natriuretic peptide levels were measured. Volume status was assessed using bioelectrical impedance analysis. Endothelial damage was evaluated by measuring asymmetric dimethylarginine expression, while echocardiography and life quality assessed by Short Form-12 Health Survey were conducted at baseline and after treatment. Results: The median daily dose of sacubitril/valsartan in 32 participants was 200 mg, and no obvious adverse reactions were reported. The defined daily dose of other antihypertensive drugs (baseline 2.00 ± 1.18, end point 1.46 ± 1.30, t = 3.216, p = 0.003) reduced significantly. After treatment with sacubitril/valsartan, left ventricular ejection fraction significantly increased from 64.81 ± 8.16% to 67.55 ± 5.85% (t = −4.022, p ≤ 0.001) and the thickness of posterior wall of the left ventricle reduced from 1.05 ± 0.14 cm to 1.00 ± 0.11 cm (t = 2.063, p = 0.048). The interventricular septal thickness (baseline 1.08 ± 0.16 cm, endpoint 1.02 ± 0.12 cm, t = 2.260, p = 0.031) remarkably reduced by the end of follow-up. The tricuspid regurgitation pressure gradient decreased from 28.47 ± 8.26 mm Hg at baseline to 23.79 ± 6.61 mm Hg (t = 2.531, p = 0.020) after treatment. Conclusion: Sacubitril/valsartan effectively manages hypertension in hemodialysis patients and may also independently improve left ventricular hypertrophy and systolic function, regardless of changes in the blood pressure or the volume load. [ABSTRACT FROM AUTHOR]

We explored the sex difference in lung ischemia–reperfusion injury (LIRI) and the role and mechanism of estrogen (E2) and angiotensin II (Ang II) in LIRI. We established a model of LIRI in mice. E2, Ang II, E2 inhibitor (fulvestrant), and angiotensin II receptor blocker (losartan) were grouped for treatment. The lung wet/dry weight ratio, natural killer (NK) cells (by flow cytometry), neutrophils (by flow cytometry), expression of key proteins (by Western blot, immunohistochemistry, ELISA, and immunofluorescence), and expression of related protein mRNA (by qPCR) were detected. The ultrastructure of the alveolar epithelial cells was observed by transmission electron microscopy. We found that E2 and Ang II played an important role in the progression of LIRI. The two signaling pathways showed obvious antagonism, and E2 regulates LIRI in the different sexes by downregulating Ang II, leading to a better prognosis. E2 and losartan reduced the inflammatory cell infiltration in lung tissue and key inflammatory factors in serum while fulvestrant and Ang II had the opposite effect. The protective effect of E2 was related with AKT, p38, COX2, and HIF-1α. [ABSTRACT FROM AUTHOR]

The article discusses a study on the association between renin levels and angiotensin II infusion dose in patients with vasopressor-dependent hypotension. The study found that baseline renin levels were predictive biomarkers for response to angiotensin II infusion and that patients with high renin levels required a higher dose of angiotensin II. The study also highlighted the potential cardiac safety of angiotensin II infusion in cardiac surgery patients. However, the study has limitations and further research is needed to confirm the findings. The text emphasizes the importance of personalized physiologic management strategies in traumatic brain injury treatment. [Extracted from the article]

Objective: To examine the associations of renin–angiotensin system (RAS) inhibitor use with postmortem brain insulin signaling and neuropathology. Methods: Among Religious Orders Study participants, 150 deceased and autopsied older individuals (75 with diabetes matched to 75 without by age at death, sex, and education) had measurements of insulin receptor substrate‐1 (IRS‐1) and RAC‐alpha serine/threonine protein kinase (AKT1) collected in the prefrontal cortex using ELISA and immunohistochemistry. Alzheimer's disease (AD), brain infarcts, and cerebral vessel pathology data were assessed by systematic neuropathologic evaluations. RAS inhibitor use was determined based on visual inspection of medication containers during study visits. The associations of RAS inhibitor use with brain insulin signaling measures and neuropathology were examined using adjusted regression analyses. Results: Of the 90 RAS inhibitor users (54 with diabetes), 65 had used only angiotensin‐converting enzyme inhibitors, 11 only angiotensin II receptor blockers, and 14 used both. RAS inhibitor use was associated with lower pT308AKT1/total AKT1, but not with pS307IRS‐1/total IRS‐1 or the density of cells stained positive for pS616 IRS‐1. RAS inhibitor use was not associated with the level of global AD pathology or amyloid beta burden, but it was associated with a lower tau‐neurofibrillary tangle density. Additionally, we found a significant interaction between diabetes and RAS inhibitors on tangle density. Furthermore, AKT1 phosphorylation partially mediated the association of RAS inhibitor use with tau tangle density. Lastly, RAS inhibitor use was associated with more atherosclerosis, but not with other cerebral blood vessel pathologies or cerebral infarcts. Interpretation: Late‐life RAS inhibitor use may be associated with lower brain AKT1 phosphorylation and fewer neurofibrillary tangles. [ABSTRACT FROM AUTHOR]

Essential hypertension can be treated with telmisartan, a strong, long-acting nonpeptide antagonist of angiotensin II type-1 (AT1) receptor. Without influencing other receptor systems involved in the regulation of the cardiovascular system, it specifically blocks the activation of the AT1 receptor by angiotensin II. When combined with high volume of distribution and telmisartan's distinctively high lipophilicity, the molecule provides the clinically significant benefit of strong tissue penetration. Additionally, it causes an increase in the protein level of adiponectin in adipocytes and activates peroxisome proliferatoractivated receptor c (PPAR-c). They might increase insulin sensitivity in this way. According to the BCS classification, it is class II medication because of its high permeability and low solubility. To increase the telmisartan solid dispersion's aqueous solubility and dissolution rate, various techniques were prepared and studied. One of the main issues with this medication is its low solubility in biological fluids, which leads to poor bioavailability after oral administration. Telmisartan's solubility was shown to be enhanced when the medication was dispersed solidly utilizing carrier such poly vinyl pyrrolidonek30, poly ethylene glycol 6000, βeta-cyclodextrin, Gelucire 43/01, Poloxamer 407, PVP K30 and HPMC E4, PEG 6000, and NaHCO3. [ABSTRACT FROM AUTHOR]

Aims: Cardiac resynchronization therapy (CRT) is an established treatment for drug‐refractory heart failure (HF) in patients with left bundle branch block (LBBB). Acute haemodynamic improvement after CRT implantation may enable the intensification of HF medication soon thereafter. Immediate pharmacotherapy intensification (IPI) after CRT implantation achieves a synergetic effect, possibly leading to a better prognosis. This study aimed to explore the incidence, characteristics, and impact of IPI on real‐world outcomes among CRT recipients with a history of hospitalization for acute HF. Methods and results: This multicentre retrospective study enrolled CRT recipients with LBBB morphology, a QRS width ≥120 ms, a left ventricular ejection fraction ≤35%, and New York Heart Association II–IV HF symptoms. All patients had previous HF hospitalizations within the previous year and received guideline‐directed medical therapy before CRT implantation. Patient baseline characteristics, including HF medication, were collected. IPI was defined as the intensification of beta‐blockers, angiotensin‐converting enzyme inhibitors, angiotensin receptor blockers, and mineralocorticoid receptor antagonists within 30 days of CRT implantation. The primary endpoint was all‐cause death or first hospitalization for HF; the secondary endpoint was all‐cause death. We enrolled 194 patients (75% male; mean age, 65 ± 13 years; 78% with non‐ischaemic cardiomyopathy). One hundred five (54%) patients received IPI. Patients who received IPI exhibited a significantly shorter QRS duration (159 ± 26 vs. 171 ± 32 ms; P = 0.004), higher estimated glomerular filtration rate (55.2 ± 20.0 vs. 47.8 ± 24.7 mL/min/1.73 m2; P = 0.022), and more dilated cardiomyopathy. During a median follow‐up period of 29 months, 70 (36%) patients reached the primary endpoint and 42 (22%) patients died. Patients with IPI showed significantly better outcomes for the primary and secondary endpoints than patients without IPI. The volumetric responder ratio at 6 months after implantation was not significantly different between patients with and without IPI; however, patients who received IPI had reduced mortality even at 6 months after implantation. In the multivariate analysis, IPI was an independent predictor of the primary endpoint (hazard ratio, 0.51; 95% confidence interval, 0.27–0.97; P = 0.043). Conclusions: Immediate intensification of HF medication was achieved in 54% of CRT recipients and was significantly higher in patients without excessive QRS prolongation, preserved renal function, and dilated cardiomyopathy than others. In patients with LBBB morphology and QRS ≥ 120 ms, IPI was associated with a significantly better prognosis and fewer HF hospitalizations after CRT implantation than others. [ABSTRACT FROM AUTHOR]

Aims: Angiotensin receptor blockers have been shown to reduce heart failure hospitalization and cardiovascular mortality in men and women with heart failure with reduced ejection fraction (HFrEF). It is unknown whether there are differences between men and women in achieved dose and treatment discontinuation due to adverse events of candesartan. Methods and results: We conducted a post hoc analysis of the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) programme. A total of 3172 men and 1106 women with HFrEF [left ventricular ejection fraction (LVEF) ≤ 40%] in New York Heart Association class II–IV were randomized to candesartan or placebo. Every 2 weeks, patients were up‐titrated from 4 or 8, to16, to 32 mg once daily, unless a higher dose was contraindicated or not tolerated. Women were older (66 vs. 64 years), had a higher LVEF (29.9% vs. 28.6%), and had more hypertension (54% vs. 47%) than men. The mean achieved dose of candesartan was 21.5 ± 12.6 mg in men and 20.7 ± 12.9 mg in women (P = 0.19). In both the candesartan and placebo groups, cardiovascular death and heart failure hospitalizations were higher in men and women who achieved lower dose levels. Event rates for achieved dose levels of 0, 4 or 8, 16, and 32 mg candesartan were 20.8, 17.2, 14.0, and 10.1 per 100 person‐years in men, respectively, and 23.6, 13.7, 14.0, and 9.1 per 100 person‐years in women, respectively. In each of the achieved dose levels, there was no sex difference in the proportion of patients with an event, neither in the candesartan group nor in the placebo group (P‐value for all > 0.05). There was no significant interaction between sex and treatment‐related discontinuation for hypotension (P = 0.520), an increase in creatinine (P = 0.102), and hyperkalaemia (P = 0.905). Conclusions: In a randomized clinical trial in patients with HFrEF, men and women achieved similar doses of candesartan. Primary event rates and treatment‐related discontinuation due to adverse events were also similar between men and women. [ABSTRACT FROM AUTHOR]

Aims: Reducing sodium intake is necessary for patients with chronic heart failure (CHF). Salt substitutes (saltSubs) have become increasingly popular as recommendations by healthcare professionals (HCPs) as well as options for patients and their caregivers. However, their consumption is generally potassium based and remains poorly evaluated in CHF management. Their impact on guideline‐directed medical therapies (GDMTs) also remains unknown. The primary objective of this study was to provide a description and estimate of HCP recommendations and reported use of saltSubs in France. Secondary objectives were to identify if there was an association between these recommendations by HCPs and the use of GDMTs. Methods and results: A nationwide, questionnaire‐based, cross‐sectional, epidemiological study was conducted from September 2020 to July 2021. Data collection included baseline characteristics, the use and recommendations of saltSubs, and the use of GDMTs, which included (i) angiotensin‐converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs) or angiotensin receptor–neprilysin inhibitors (ARNis), (ii) mineralocorticoid receptor antagonists (MRAs), and/or (iii) beta‐blockers (BBs). In total, 13% of HCPs advised saltSubs and 17% of patients and 22% of caregivers reported their consumption. CHF patients advised to take saltSubs did not differ in terms of left ventricular ejection fraction (EF) <40%, ischaemic origin, and New York Heart Association III–IV class, but were more recently hospitalized for acute HF (P = 0.004). HCPs who recommended saltSubs to patients were more likely to advise an anti‐diabetic diet (P < 0.001), cholesterol‐lowering diet (P < 0.001), and exercise (P = 0.018). In the overall population, ACEi/ARB/ARNi use was less frequent in case of saltSub recommendations (74% vs. 82%, P = 0.012). The concomitant prescription of none, one, two, or three GDMTs was less favourable in case of saltSub recommendations (P = 0.046). There was no significant difference for the presence of MRA (56% vs. 58%) and/or BB (78% vs. 82%). The under‐prescription of ACEi/ARB/ARNi was found when patients had EF < 40% (P = 0.029) and/or EF ≥ 40% (P = 0.043). In the subgroup with left ventricular EF ≥ 40%, we found a higher thiazide use (P = 0.014) and a less frequent use of low EF GDMTs (P = 0.044) in case of being recommended saltSubs. Conclusions: Beyond the well‐established risk for hyperkalaemia, our preliminary results suggest a potentially negative impact of saltSubs on GDMT use, especially for ACEis/ARBs/ARNis in CHF management. saltSub recommendations and their availability from open sale outlets should be considered to avoid possible misuse or deference from GDMTs in the future. Informed advice to consumers should also be considered from HCPs or pharmacists. [ABSTRACT FROM AUTHOR]

Renin-angiotensin system (RAS) modulators, including Angiotensin receptor blockers (ARB) and angiotensin-converting enzyme inhibitors (ACEI), are effective medications for controlling blood pressure. Cognitive deficits, including lack of concentration, memory loss, and confusion, were reported after COVID-19 infection. ARBs or ACEI increase the expression of angiotensin-converting enzyme-2 (ACE-2), a functional receptor that allows binding of SARS-CoV-2 spike protein for cellular invasion. To date, the association between the use of RAS modulators and the severity of COVID-19 cognitive dysfunction is still controversial. Purpose: This study addressed the following questions: 1) Does prior treatment with RAS modulator worsen COVID-19-induced cerebrovascular and cognitive dysfunction? 2) Can post-treatment with RAS modulator improve cognitive performance and cerebrovascular function following COVID-19? We hypothesize that pre-treatment exacerbates COVID-19-induced detrimental effects while post-treatment displays protective effects. Methods: Clinical study: Patients diagnosed with COVID-19 between May 2020 and December 2022 were identified through the electronic medical record system. Inclusion criteria comprised a documented medical history of hypertension treated with at least one antihypertensive medication. Subsequently, patients were categorized into two groups: those who had been prescribed ACEIs or ARBs before admission and those who had not received such treatment before admission. Each patient was evaluated on admission for signs of neurologic dysfunction. Pre-clinical study: Humanized ACE-2 transgenic knock-in mice received the SARS-CoV-2 spike protein via jugular vein injection for 2 weeks. One group had received Losartan (10 mg/kg), an ARB, in their drinking water for two weeks before the injection, while the other group began Losartan treatment after the spike protein injection. Cognitive functions, cerebral blood flow, and cerebrovascular density were determined in all experimental groups. Moreover, vascular inflammation and cell death were assessed. Results: Signs of neurological dysfunction were observed in 97 out of 177 patients (51%) taking ACEIs/ARBs prior to admission, compared to 32 out of 118 patients (27%) not receiving ACEI or ARBs. In animal studies, spike protein injection increased vascular inflammation, increased endothelial cell apoptosis, and reduced cerebrovascular density. In parallel, spike protein decreased cerebral blood flow and cognitive function. Our results showed that pretreatment with Losartan exacerbated these effects. However, post-treatment with Losartan prevented spike protein-induced vascular and neurological dysfunctions. Conclusion: Our clinical data showed that the use of RAS modulators before encountering COVID-19 can initially exacerbate vascular and neurological dysfunctions. Similar findings were demonstrated in the in-vivo experiments; however, the protective effects of targeting the RAS become apparent in the animal model when the treatment is initiated after spike protein injection. [ABSTRACT FROM AUTHOR]

Recently, a mild elevation of the blood ketone levels was found to exert multifaceted cardioprotective effects. To investigate the effect of angiotensin receptor neprilysin inhibitors (ARNIs) on the blood ketone body levels, 46 stable pre-heart failure (HF)/HF patients were studied, including 23 who switched from angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) to ARNIs (ARNI group) and 23 who continued treatment with ACE inhibitors or ARBs (control group). At baseline, there were no significant differences in the total ketone body (TKB) levels between the two groups. Three months later, the TKB levels in the ARNI group were higher than the baseline values (baseline to 3 months: 71 [51, 122] to 92 [61, 270] μmol/L, P < 0.01). In the control group, no significant change was observed between the baseline and 3 months later. A multiple regression analysis demonstrated that the initiation of ARNI and an increase in the blood non-esterified fatty acid (NEFA) levels at 3 months increased the percentage changes in the TKB levels from baseline to 3 months (%ΔTKB level) (initiation of ARNI: P = 0.017, NEFA level at 3 months: P < 0.001). These results indicate that ARNI administration induces a mild elevation of the blood TKB levels in pre-HF/HF patients. [ABSTRACT FROM AUTHOR]

There is conflicting evidence in select mouse models and humans that suggest angiotensin‐converting enzyme 2 expression is increased due to treatment with angiotensin converting enzyme inhibitors and angiotensin receptor blockers (ACEI/ARBs). Given the wide range of conditions that these medications treat, further evaluation is necessary to determine safety in the context of COVID‐19. We sought to determine the association between use of ACEI/ARBs and COVID‐19 severity in patients with essential hypertension. We included 714 patients with essential hypertension diagnosed with COVID‐19 and admitted to University of Iowa Healthcare from March 1, 2020 to June 29, 2021. Severity of COVID‐19 infection was assessed based on mortality, length of stay in hospital, intensive care unit admission, and use of supplemental oxygen, invasive ventilation, and vasopressors. Multivariable logistic and linear regression analyses were used for binary and continuous outcomes, respectively. Prior exposure to ACEI/ARBs before admission was significantly associated with lower mortality (OR: 0.454, p = .015), shorter length of stay in hospital (p < .001), and decreased adjusted odds of intensive care admission (OR: 0.719; p < .042). The present results suggest that patients with essential hypertension hospitalized with COVID‐19 who had a prescription for ACEI/ARBs prior to admission exhibited less severe COVID‐19 and lower in‐hospital mortality. [ABSTRACT FROM AUTHOR]

Heart failure remains a leading cause of morbidity and mortality worldwide. Current treatment for patients with heart failure include drugs targeting G protein‐coupled receptors such as β‐adrenoceptor antagonists (β‐blockers) and angiotensin II type 1 receptor antagonists (or angiotensin II receptor blockers). However, many patients progress to advanced heart failure with persistent symptoms, despite treatment with available therapeutics that have been shown to reduce mortality and mortality. GPCR targets currently being explored for the development of novel heart failure therapeutics include adenosine receptor, formyl peptide receptor, relaxin/insulin‐like family peptide receptor, vasopressin receptor, endothelin receptor and the glucagon‐like peptide 1 receptor. Many GPCR drug candidates are limited by insufficient efficacy and/or dose‐limiting unwanted effects. Understanding the current challenges hindering successful clinical translation and the potential to overcome existing limitations will facilitate the future development of novel heart failure therapeutics. LINKED ARTICLES: This article is part of a themed issue Therapeutic Targeting of G Protein‐Coupled Receptors: hot topics from the Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists 2021 Virtual Annual Scientific Meeting. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v181.14/issuetoc [ABSTRACT FROM AUTHOR]

Background: Telmisartan, a potent angiotensin II type-1 receptor blocker as well as partial PPAR–gamma agonist, has emerged as a versatile therapeutic agent with diverse pharmacological actions beyond its primary indication for essential hypertension. This review explores the complex mechanisms of action of telmisartan and clarifies its effectiveness in an inflammation, cancer, metabolic, and CNS disorders. Main body: Telmisartan inhibits many biochemical processes involved in the control of the cardiovascular system, such as vascular smooth muscle contraction, aldosterone production, and sympathetic tone modulation, by specifically targeting the angiotensin II type-1 receptor. Its distinct partial agonist action toward peroxisome proliferator-activated receptor gamma also imparts anti-inflammatory, antiproliferative, and antioxidant activities, making it a viable treatment for various diabetic patients who have atherosclerosis and myocardial infarction. Conclusion: Telmisartan's diverse pharmacological actions, encompassing anti-inflammatory, neuroprotective, nephroprotective, anticancer, and anti-anxiety properties, position it as a promising treatment option for a broad spectrum of medical conditions. [ABSTRACT FROM AUTHOR]

Background: Hypertension among persons with childbearing potential is on the rise. Maintaining proper blood pressure during pregnancy is vital to prevent maternal and neonatal complications. Yet, limited evidence on the risk-benefit of various antihypertensives presents challenges for informed decision-making during this critical period. This study aimed to examine the utilization patterns of different classes of antihypertensives among persons with pre-existing hypertension before, during, and after pregnancy. Methods: We used MarketScan® Commercial Database 2011−2020 to analyze antihypertensive utilization among pregnant persons aged 12 to 55 identified via a validated algorithm. Pre-existing hypertension was defined as ≥1 inpatient or ≥2 outpatient encounters for hypertension within the 180 days preceding the LMP. Antihypertensive utilization was described during target periods: 0–3 months (0-3M) before pregnancy, 1st/2nd/3rd trimester (T1/2/3), 0-3M, and 4-6M after pregnancy. Results: We identified 1,950,292 pregnancies, of which 20,576 (12,978 live and 7,598 non-live) had pre-existing hypertension. Both groups had similar antihypertensive use (80.1% and 81.0%, respectively) during the 6 months before pregnancy (baseline). For live-birth pregnancies, 13.9% of baseline users discontinued treatment during pregnancy, while 28.9% of non-users initiated antihypertensives during pregnancy, and 17.2% started postpartum. Before pregnancy, the predominant antihypertensives included thiazide diuretics (21.9%), combined α- and β-blockers (18.4%), and dihydropyridines (16.2%). During pregnancy, thiazide diuretics, cardioselective β-blockers, and ACE inhibitors declined (T3: 3.0%, 4.2%, and 0.8%). Dihydropyridine use was steady during pregnancy, but preference shifted from amlodipine to nifedipine in T3 (2.2.% vs.10.8%). Central α2‐agonists increased during pregnancy (up to 15.2% in T3) compared to both pre- (9.8%) and post-pregnancy (5.7%). ARBs mirrored ACE inhibitors, with less than 1% utilization in later trimesters. Combination agents dropped from 10.8% pre-pregnancy to 0.8% in T3, then rebounded to 7.3% post-pregnancy. Conclusion: Research is warranted to evaluate the choice of antihypertensives and optimal timing to switch to safer alternatives, considering maternal and fetal outcomes. [ABSTRACT FROM AUTHOR]

Background/Objectives: Coronary artery disease, a leading global cause of death, highlights the essential need for early detection and management of modifiable cardiovascular risk factors to prevent further coronary events. Methods: This study, conducted at a major tertiary academic PCI-capable hospital in Romania from 1 January 2011 to 31 December 2013, prospectively analyzed 387 myocardial infarction with ST-segment elevation (STEMI) patients to assess the long-term management of modifiable risk factors. This study particularly focused on patients with new-onset left bundle branch block (LBBB) and compared them with a matched control group without LBBB. Results: During median follow-up periods of 9.6 years for LBBB patients and 9.2 years for those without LBBB, it was found that smoking, obesity, and dyslipidemia were prevalent in 73.80%, 71.42%, and 71.42% of the LBBB group, respectively, at baseline. Significant reductions in smoking were observed in both groups, with the LBBB group's smoking rates decreasing significantly to 61.90% (p = 0.034). Patients with LBBB more frequently achieved low-density lipoprotein cholesterol (LDLc) target levels during the follow-up period (from 71.42% to 59.52%; p = 0.026) compared to the control group (from 66.67% to 71.42%; p = 0.046). Prescription rates for dual antiplatelet therapy (DAPT), angiotensin-converting enzyme inhibitors (ACEi) or angiotensin II receptor blockers (ARBs), beta-blockers, and statins were initially high but then decreased by the follow-up. Statin use was reduced from 97.62% to 69.04% (p = 0.036) in the LBBB group and from 100% to 61.90% (p = 0.028) in the non-LBBB group. This study also highlighted moderate correlations between obesity (r = 0.627, p = 0.040) and subsequent coronary reperfusion in the LBBB group, while dyslipidemia and smoking showed very strong positive correlations across both groups (dyslipidemia: r = 0.903, p = 0.019 for LBBB; r = 0.503, p = 0.048 for non-LBBB; smoking: r = 0.888, p = 0.035 for LBBB; r = 0.517, p = 0.010 for non-LBBB). Conclusions: These findings underscore the crucial need for targeted management of modifiable risk factors, particularly focusing on dyslipidemia and smoking cessation, to improve subsequent coronary reperfusion outcomes post-STEMI, especially in patients with complicating factors like LBBB. [ABSTRACT FROM AUTHOR]

Introduction: Angiotensin receptor blockers are widely used antihypertensive drugs in South Korea. In 2021, the Korea Ministry of Food and Drug Safety acknowledged the need for national compensation for a drug-induced liver injury (DILI) after azilsartan use. However, little is known regarding the association between angiotensin receptor blockers and DILI. Objective: We conducted a retrospective cohort study in incident users of angiotensin receptor blockers from a common data model database (1 January, 2017–31 December, 2021) to compare the risk of DILI among specific angiotensin receptor blockers against valsartan. Methods: Patients were assigned to treatment groups at cohort entry based on prescribed angiotensin receptor blockers. Drug-induced liver injury was operationally defined using the International DILI Expert Working Group criteria. Cox regression analyses were conducted to derive hazard ratios and the inverse probability of treatment weighting method was applied. All analyses were performed using R. Results: In total, 229,881 angiotensin receptor blocker users from 20 university hospitals were included. Crude DILI incidence ranged from 15.6 to 82.8 per 1000 person-years in treatment groups, most were cholestatic and of mild severity. Overall, the risk of DILI was significantly lower in olmesartan users than in valsartan users (hazard ratio: 0.73 [95% confidence interval 0.55–0.96]). In monotherapy patients, the risk was significantly higher in azilsartan users than in valsartan users (hazard ratio: 6.55 [95% confidence interval 5.28–8.12]). Conclusions: We found a significantly higher risk of suspected DILI in patients receiving azilsartan monotherapy compared with valsartan monotherapy. Our findings emphasize the utility of real-world evidence in advancing our understanding of adverse drug reactions in clinical practice. [ABSTRACT FROM AUTHOR]

Evidence supports the use of angiotensin-converting enzyme inhibitors (ACEis) and angiotensin-receptor blockers (ARBs) in patients with hypertension and stage 3 or milder chronic kidney disease (CKD). This systematic review and individual-level meta-analysis summarizes the evidence supporting the use of the medications in patients with hypertension and more advanced CKD. Background: In patients with advanced chronic kidney disease (CKD), the effects of initiating treatment with an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin-receptor blocker (ARB) on the risk for kidney failure with replacement therapy (KFRT) and death remain unclear. Purpose: To examine the association of ACEi or ARB treatment initiation, relative to a non–ACEi or ARB comparator, with rates of KFRT and death. Data Sources: Ovid Medline and the Chronic Kidney Disease Epidemiology Collaboration Clinical Trials Consortium from 1946 through 31 December 2023. Study Selection: Completed randomized controlled trials testing either an ACEi or an ARB versus a comparator (placebo or antihypertensive drugs other than ACEi or ARB) that included patients with a baseline estimated glomerular filtration rate (eGFR) below 30 mL/min/1.73 m 2. Data Extraction: The primary outcome was KFRT, and the secondary outcome was death before KFRT. Analyses were done using Cox proportional hazards models according to the intention-to-treat principle. Prespecified subgroup analyses were done according to baseline age (<65 vs. ≥65 years), eGFR (<20 vs. ≥20 mL/min/1.73 m 2), albuminuria (urine albumin–creatinine ratio <300 vs. ≥300 mg/g), and history of diabetes. Data Synthesis: A total of 1739 participants from 18 trials were included, with a mean age of 54.9 years and mean eGFR of 22.2 mL/min/1.73 m 2 , of whom 624 (35.9%) developed KFRT and 133 (7.6%) died during a median follow-up of 34 months (IQR, 19 to 40 months). Overall, ACEi or ARB treatment initiation led to lower risk for KFRT (adjusted hazard ratio, 0.66 [95% CI, 0.55 to 0.79]) but not death (hazard ratio, 0.86 [CI, 0.58 to 1.28]). There was no statistically significant interaction between ACEi or ARB treatment and age, eGFR, albuminuria, or diabetes (P for interaction > 0.05 for all). Limitation: Individual participant–level data for hyperkalemia or acute kidney injury were not available. Conclusion: Initiation of ACEi or ARB therapy protects against KFRT, but not death, in people with advanced CKD. Primary Funding Source: National Institutes of Health. (PROSPERO: CRD42022307589) [ABSTRACT FROM AUTHOR]

Both hypertension and aging are known to increase the vulnerability of the brain to neurovascular damage, resulting in cognitive impairment. The present study investigated the efficacy of the antihypertensive drug losartan on age- and hypertension-associated cognitive decline and the possible mechanism underlying its effect in spontaneously hypertensive rats (SHRs). Losartan was administered (10 mg/kg, i.p. for 19 days) to 3- and 14-month-old SHRs. Age-matched Wistar rats were used as controls. Working memory, short-term object recognition, and spatial memory were assessed using the Y-maze, object recognition test (ORT) and radial arm maze (RAM) test. The expression of markers associated with aging, oxidative stress, and memory-related signaling was assessed in the frontal cortex (FC) and hippocampus. Motor activity measured over 24 h was not different between groups. Middle-aged vehicle-treated SHRs showed poorer performance in spontaneous alternation behavior (SAB) and activity in the first Y-maze test than their younger counterparts, suggesting age-related reduced "decision making" and reactivity in a novel environment. Losartan improved the age- and hypertension-induced decline in short-term recognition and spatial memory measured in the ORT and the second Y-maze test, particularly in the middle-aged rats, but was ineffective in the young adult rats. Changes in memory and age-related markers such as cAMP response element-binding protein (CREB) and amyloid-β1–42 (Aβ1–42) and increased oxidative stress were observed in the hippocampus but not in the FC between young adult and middle-aged vehicle-treated SHRs. Losartan increased CREB expression while reducing Aβ1–42 levels and concomitant oxidative stress in middle-aged SHRs compared with vehicle-treated SHRs. In conclusion, our study highlights the complex interplay between hypertension, aging, and cognitive impairment. It suggests that there is a critical time window for therapeutic intervention with angiotensin II type 1 receptor blockers. [ABSTRACT FROM AUTHOR]

The aim of this cross-sectional study was to evaluate the differences in the levels of advanced glycation end products (AGE) between patients with chronic kidney disease (CKD) and kidney transplant recipients (KTRs) and to investigate the risk factors for the AGE levels in each group of these patients. There were 217 participants total, of which 99 (45.6%) were KTRs and 118 (54.4%) had CKD. Data on the levels of AGE, body mass composition, anthropometric parameters, central and peripheral blood pressure, and clinical and laboratory parameters were gathered for each study participant. The AGE values of the CKD and KTRs groups did not differ from one another. In both groups, a lower estimated glomerular filtration rate, male sex, and older age were positive predictors for increased AGE values. Furthermore, higher levels of AGE were linked to lower central systolic blood pressure (cSBP) in the CKD group, whilst, in the KTRs group, higher levels of AGE were linked to a shorter time since kidney transplantation (KTx), more years of dialysis prior to KTx, lower levels of trunk visceral fat, the presence of arterial hypertension, and the absence of prescriptions for the antihypertensive medications urapidil and angiotensin II receptor blockers. Further studies are needed to better understand the above associations. Consequently, a personalised multidisciplinary approach to assess the cardiovascular as well as dietary and lifestyle risk factors to reduce the AGE levels in both KTRs and CKD patients may be implemented. [ABSTRACT FROM AUTHOR]

Background: There have been several recent advances in the care of patients with chronic kidney disease (CKD), including the use of sodium glucose cotransporter 2 (SGLT2) inhibitors and selective mineralocorticoid receptor antagonists (MRAs). There are very few data reporting the outcomes of these treatments in real-world experience. The aim of this retrospective study is to report the effects of SGLT2 inhibitors, finerenone, and their combination in CKD patients in our community-based setting. Methods: Ninety-eight patients with CKD with an estimated glomerular filtration rate (eGFR) between 25 and 90 mL/min per 1.73 m2 and a urine albumin-to-creatinine ratio (UACR) ≥ 30 mg/g were included. Patients were divided into three groups: two monotherapy groups of SGLT2 inhibitors or finerenone and a third combination group of therapy with SGLT2 inhibitors for the first 4 months and SGLT2 inhibitors and finerenone subsequently. The primary outcomes were the timing and percentage of patients achieving a >50% reduction in UACR from baseline. Results: Group 1 comprised 52 patients on SGLT2i, group 2 had 22 patients on finerenone, and group 3 had 24 patients on combination therapy. The baseline median UACR and mean eGFR were 513 mg/g and 47.9 mL/min per 1.73 m2 in group 1, 548.0 mg/g and 50.5 mL/min per 1.73 m2 in group 2, and 800 mg/g and 60 mL/min per 1.73 m2 in group 3. At baseline, 71 (72.4%) patients were on the angiotensin-converting enzyme inhibitor (ACEi) or the angiotensin receptor blocker (ARB), and 78 (79.5%) patients had type 2 diabetes. After 8 months of follow-up, a >50% decrease in albuminuria was achieved in 96% of patients in group 3, compared to 50% in group 1 and 59% in group 2 (p-values were <0.01 and <0.01, respectively). There was a statistically but not clinically significant change in mean potassium levels in group 2 (+0.4 mmol/L) compared to either group 1 (0.0 mmol/L with p-value: <0.01) or group 3 (−0.01 mmol/L with p-value: <0.01). However, there was no difference in potassium levels when comparing groups 1 and 3. At the end of the follow-up, the average difference in eGFR was −3.4 (8.8), −5.3(10.1), and −7.8 (11.2) mL/min per 1.73 m2 in groups 1, 2, and 3, respectively, without a statistically significant difference between groups. Conclusions: In this real-world experience in our community setting, the combination of SGLT2 inhibitors and finerenone in our adult patients with CKD was associated with a very significant and clinically relevant reduction in UACR, without an increased risk of hyperkalemia. Combination therapy of SGLT2 inhibitor and finerenone regarding background use of ACEi/ARB is feasible and should be encouraged for further albuminuria reductions in CKD patients. [ABSTRACT FROM AUTHOR]

Background The association between angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) and severe acute respiratory syndrome coronavirus 2 susceptibility, particularly via ACE-2 receptor upregulation in the kidneys, raises concerns about potential kidney disease risks in long coronavirus disease (COVID) patients. This study explores the association of ACEI/ARB therapy on acute kidney injury (AKI), chronic kidney disease (CKD) and all-cause mortality in patients with and without long COVID. Methods A retrospective cohort study using TriNetX datasets was conducted, with diagnoses of long COVID via International Classification of Diseases, Tenth Revision (ICD-10) codes and prescription for ACEI/ARB as the classification of four cohorts: long COVID ACEI/ARB users (LCAUs), long COVID ACEI/ARB non-users (LCANs), non-long COVID ACEI/ARB users (NLCAUs) and non-long COVID ACEI/ARB non-users (NLCANs). Multivariable stratified Cox proportional hazards regression models assessed the adjusted hazard ratios (aHRs) across groups. Additional analyses were conducted, including time-dependent exposure analysis and comparison with an active comparator, calcium channel blockers. Results Our study included 18 168 long COVID and 181 680 propensity score-matched non-long COVID patients from October 2021 to October 2023. ACEI/ARB use did not significantly affect the risk of AKI or CKD when comparing LCAUs with LCANs and NLCAUs with NLCANs. However, a protective effect against all-cause mortality was observed {aHR 0.79 [95% confidence interval (CI) 0.65–0.93]} in the NLCAU group compared with the NLCAN group. Conversely, long COVID was associated with increased risks of CKD [aHR 1.49 (95% CI 1.03–2.14)] and all-cause mortality [aHR 1.49 (95% CI 1.00–2.23)] when comparing LCANs with NLCANs. The additional analyses support the primary findings. Conclusions ACEI/ARB treatment does not increase the incidence of CKD or AKI, regardless of long COVID status. However, long COVID itself is associated with increasing risks of kidney diseases and all-cause mortality. [ABSTRACT FROM AUTHOR]

Blood pressure and fluid balance are regulated hormonally by renin-angiotensin system (RAS). Influence on this system could be achieved by different compounds that act as angiotensin-converting enzyme inhibitors (ACE inhibitors), angiotensin receptor blockers and renin inhibitors. The purpose of the present study is to predict the structures of the potent ACE inhibitors on the base of His-Leu peptide structural element of angiotensine I using computational methods. Different modifications were made in the structure of this dipeptide and the energy of binding with the enzyme were calculated. The docking results were analyzed and it was found that along with the important amino acid residue of the receptor molecule Arg167, the Tyr residues (35, 87, 88 and 92) as well as Cys180 are extremely important for the strong binding to the receptor and, accordingly, the manifestation of antagonistic action by the analogues. To block the receptor, the ligand molecule must have an intact terminal carboxyl group and an imidazole nucleus to participate in appropriate interactions. The inclusion of functional groups in the side chains of the amino acid residues of the dipeptide create an additional site for binding to the receptor. With the help of docking, the ligand molecule can be optimized, and this process is fast, saving the synthesis of many compounds and their biological testing. And finally, the most potent analogues will be synthesized and biologically tested. [ABSTRACT FROM AUTHOR]

This article provides information on the management of diabetic kidney disease (DKD) in patients with type 2 diabetes. The primary treatment for DKD is the use of ACE inhibitors and angiotensin receptor blockers (ARBs), which can reduce proteinuria and slow the progression of chronic kidney disease (CKD). Sodium-glucose cotransporter-2 (SGLT-2) inhibitors and finerenone, a nonsteroidal mineralocorticoid receptor antagonist, are also recommended to reduce CKD progression and cardiovascular events. It is important to monitor patients for potential side effects and adjust treatment accordingly. Additionally, GLP-1 receptor agonists can be used to improve glycemic control and have shown benefits for CKD and cardiovascular health. All patients with diabetes should be screened for DKD and considered for appropriate therapy. [Extracted from the article]

Background: Surgical patients with aortic dissection often require multiple antihypertensive drugs to control blood pressure. However, the prescription pattern and effectiveness of antihypertensive drugs for these patients are unclear. We aimed to investigate the prescription pattern and effectiveness of different classes of antihypertensive drugs in surgical patients with aortic dissection. Methods: Newly diagnosed aortic dissection patients who underwent surgery, aged >20 years, from 1 January 2012 to 31 December 2017 were identified. Patients with missing data, in-hospital mortality, aortic aneurysms, or congenital connective tissue disorders, such as Marfan syndrome, were excluded. Prescription patterns of antihypertensive drugs were identified from medical records of outpatient visits within 90 days after discharge. Antihypertensive drugs were classified into four classes: 1) β-blockers, 2) calcium channel blockers (CCBs), 3) renin-angiotensin system, and 4) other antihypertensive drugs. Patients were classified according to the number of classes of antihypertensive drugs as follows: 1) class 0, no exposure to antihypertensive drugs; 2) class 1, antihypertensive drugs of the same class; 3) class 2, antihypertensive drugs of two classes; 4) class 3, antihypertensive drugs of three classes; or 5) class 4, antihypertensive drugs of four classes. The primary composite outcomes included rehospitalization associated with aortic dissection, death due to aortic dissection, and all-cause mortality. Results: Most patients were prescribed two (28.87%) or three classes (28.01%) of antihypertensive drugs. In class 1, β-blockers were most commonly used (8.79%), followed by CCBs (5.95%). In class 2, β-blockers+CCB (10.66%) and CCB+RAS (5.18%) were the most common drug combinations. In class 3, β-blockers + CCB+RAS (14.84%) was the most prescribed combination. Class 0 had a significantly higher hazard of the composite outcome (HR, 2.1; CI, 1.46-3.02; p < 0.001) and all-cause mortality (HR, 2.34; CI, 1.56-3.51; p < 0.001) than class 1. There were no significant differences in hazards for rehospitalization associated with aortic dissection among classes. Conclusion: Among operated patients with type A aortic dissection, no specific type of antihypertensive drug was associated with a better outcome, whereas among those with type B aortic dissection, the use of β-blockers and CCBs was related to a significantly lower risk of the composite outcome. [ABSTRACT FROM AUTHOR]

Purpose: Tanshinone IIA (Tan-IIA) is widely used in patients with diabetic nephropathy (DN), but its protective effect on podocytes in DN has not been well studied. In this study, the effects of Tan-IIA on autophagy and inflammation of glomerular podocytes in DN were observed in vivo and in vitro, and the underlying mechanisms were investigated. Irbesartan, an angiotensin II receptor blocker, is a representative medication for the clinical treatment of DN. So irbesartan was chosen as a positive control drug. Methods: Eight-week-old male db/db mice were randomly divided into a DN group, an irbesartan group, and three groups receiving different doses of Tan-IIA. The control group consisted of the db/m littermate mice. Blood, urine, and kidney samples were taken from the mice after 12 weeks of continuous administration. Renal protection of Tan-IIA was evaluated using enzyme-linked immunosorbent assay kits, haematoxylin and eosin staining, transmission electron microscopy, Western blotting, and immunohistochemistry. In vitro, the protective effect of Tan-IIA on podocytes was explored using MPC5 cells cultured with high glucose. Results: Tan-IIA significantly improved renal pathological injury and relieved the renal dysfunction in DN. Compared with the DN group, Tan-IIA could up-regulate the expression of Synaptopodin, Podocin, LC3II/I and Beclin-1 (p < 0.05), and down-regulate the expression of p62, F4/80, NF-κB p65, IL-1β, TNF-α and IL-6 (p < 0.05) both in vivo and in vitro, suggesting that Tan-IIA treatment alleviated podocyte injury by promoting autophagy and inhibiting inflammation during DN. The levels of p-PI3K/PI3K, p-Akt/Akt and p-mTOR/mTOR in Tan-IIA group were lower than those in DN group (p < 0.05), indicating that Tan-IIA inhibited the PI3K/Akt/mTOR signalling pathway in podocytes, which was a key pathway in regulating both autophagy and inflammation. Conclusion: Tan-IIA prevented podocyte injury in DN by fostering autophagy and inhibiting inflammation, at least in part via inhibition of the PI3K/Akt/mTOR signalling pathway. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the patient survival rates based on the use of angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB) in a large cohort of patients undergoing maintenance hemodialysis (HD). Data from a national HD quality assessment program were used in this retrospective study. The patients were classified into four groups based on the use of renin-angiotensin system blockers (RASBs) as follows: No group, patients without a prescription of any anti-hypertensive drugs including RASBs; Other group, patients with a prescription of anti-hypertensive drugs excluding RASBs; ACEI group, patients with a prescription of an ACEI; and ARB group, patients with a prescription of an ARB. The 5-year survival rates in the no, other, ACEI, and ARB groups were 68.6%, 67.8%, 70.6%, and 69.2%, respectively. The ACEI group had the best patient survival trend among the four groups. In multivariable Cox regression analyses, no differences were observed between the ACEI and ARB groups. Among young patients and patients without diabetes or heart disease, the ACEI group had the best patient survival among the four groups. However, among patients with DM or heart disease, the ARB group had the best patient survival. Our study found that patients receiving ACEI and ARB had comparable survival. However, patients receiving ARB had better survival in the subgroups of patients with DM or heart disease, and patients receiving ACEI had better survival in the subgroup of young patients or patients without diabetes or heart disease. [ABSTRACT FROM AUTHOR]

Background: Nocturnal blood pressure (BP) is correlated with an increased risk of cardiovascular events and is an important predictor of cardiovascular death in hypertensive patients. Objective: Nocturnal BP control is of great importance for cardiovascular risk reduction. This systematic review and meta-analysis aimed to explore the efficacy of angiotensin receptor blockers (ARBs) for nocturnal BP reduction in patients with mild to moderate hypertension. Methods: PICOS design structure was used to formulate the data extraction. All statistical calculations and analyses were performed with R. Results: Seventy-seven studies with 13,314 participants were included. The overall analysis indicated that nocturnal BP drop varied considerably among different ARBs. Allisartan (13.04 [95% CI (-18.41, -7.68)] mmHg), olmesartan (11.67 [95% CI (-14.12, -9.21)] mmHg), telmisartan (11.11 [95% CI (-12.12, -10.11)] mmHg) were associated with greater reduction in nocturnal systolic BP. In the aspect of the nocturnal-diurnal BP drop ratio, only allisartan was greater than 1. While, the variation tendency of last 4-6h ambulatory BP was basically consistent with nocturnal BP. Additionally, allisartan showed improvement effect in the proportion of patients with dipping BP pattern. Conclusions: This study demonstrates that for patients with mild to moderate hypertension, allisartan, olmesartan and telmisartan have more advantages in nocturnal BP reduction among the ARBs, while allisartan can reduce nighttime BP more than daytime BP and improve the dipping pattern. [ABSTRACT FROM AUTHOR]

Key Points: Question: Does the benefit of renin-angiotensin system (RAS) blockers in patients with heart failure and reduced ejection fraction differ between Black and non-Black patients? Findings: In this meta-analysis involving more than 16 000 patients from 5 randomized trials, the mortality benefit from RAS blockade was similar in Black and non-Black patients. Although the relative risk reduction in hospitalizations for heart failure was smaller in Black patients, the absolute benefit was comparable in the 2 groups given the greater incidence of hospitalization in Black patients. Meaning: RAS blockers are effective at improving cardiovascular outcomes in Black and non-Black patients with heart failure. Importance: Concerns have arisen that renin-angiotensin system (RAS) blockers are less effective in Black patients than non-Black patients with heart failure and reduced ejection fraction (HFrEF). Objective: To determine whether the effects of RAS blockers on cardiovascular outcomes differ between Black patients and non-Black patients with HFrEF. Data Sources: MEDLINE and Embase databases through December 31, 2023. Study Selection: Randomized trials investigating the effect of RAS blockers on cardiovascular outcomes in adults with HFrEF that enrolled Black and non-Black patients. Data Extraction and Synthesis: Individual-participant data were extracted following Preferred Reporting Items for Systematic Reviews and Meta-analyses Independent Personal Data (PRISMA-IPD) reporting guidelines. Effects were estimated using a mixed-effects model using a 1-stage approach. Main Outcome and Measure: The primary outcome was first hospitalization for HF or cardiovascular death. Results: The primary analysis, based on the 3 placebo-controlled RAS inhibitor monotherapy trials, included 8825 patients (9.9% Black). Rates of death and hospitalization for HF were substantially higher in Black than non-Black patients. The hazard ratio (HR) for RAS blockade vs placebo for the primary composite was 0.84 (95% CI, 0.69-1.03) in Black patients and 0.73 (95% CI, 0.67-0.79) in non-Black patients (P for interaction =.14). The HR for first HF hospitalization was 0.89 (95% CI, 0.70-1.13) in Black patients and 0.62 (95% CI, 0.56-0.69) in non-Black patients (P for interaction =.006). Conversely, the corresponding HRs for cardiovascular death were 0.83 (95% CI, 0.65-1.07) and 0.84 (95% CI, 0.77-0.93), respectively (P for interaction =.99). For total hospitalizations for HF and cardiovascular deaths, the corresponding rate ratios were 0.82 (95% CI, 0.66-1.02) and 0.72 (95% CI, 0.66-0.80), respectively (P for interaction =.27). The supportive analyses including the 2 trials adding an angiotensin receptor blocker to background angiotensin-converting enzyme inhibitor treatment (n = 16 383) gave consistent findings. Conclusions and Relevance: The mortality benefit from RAS blockade was similar in Black and non-Black patients. Despite the smaller relative risk reduction in hospitalization for HF with RAS blockade in Black patients, the absolute benefit in Black patients was comparable with non-Black patients because of the greater incidence of this outcome in Black patients. This meta-analysis assesses whether Black patients with heart failure and reduced ejection fraction respond differently than patients of other races to renin-angiotensin system (RAS) blockade by examining individual patient data from randomized clinical trials. [ABSTRACT FROM AUTHOR]