BACKGROUND: Poststroke epilepsy (PSE) is a common complication after ischemic stroke. This study investigates the association between the use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) and the risk of PSE in patients with ischemic stroke.
RESULTS: A population-based retrospective cohort study was conducted using Taiwan\'s National Health Insurance Research Database between 2000 and 2015. Patients with hypertension with a history of ischemic stroke were classified into prevalent, new, and nonusers according to their use of ACEIs/ARBs. Prevalent ACEI/ARB users were further classified into continuing or discontinued users, based on their poststroke medication adherence. We used multivariate Cox regression models, adjusted for demographics and comorbidities, to assess the risk of PSE among different ACEI/ARB user groups. There were 182 983 ACEI/ARB users and 38 365 nonusers included. There were 7387 patients diagnosed with PSE, whereas 213 961 were not. Nonusers exhibited a higher risk of PSE (adjusted hazard ratio [aHR], 1.72 [95% CI, 1.63-1.82]). Both prevalent and nonusers had higher risks compared with new ACEI/ARB users, with respective aHRs of 1.33 (95% CI, 1.25-1.41) and 2.00 (95% CI, 1.87-2.14). Discontinued ACEI/ARB users showed the highest risk of PSE (aHR, 2.34 [95% CI, 2.15-2.54]), suggesting the importance of continuing ACEI/ARB use after stroke. Treatment-by-age interaction was significant among patients with or without ACEI/ARB use before stroke (P value for interaction 0.004 and <0.001, respectively), suggesting a stronger beneficial association in younger patients.
CONCLUSIONS: The use of ACEIs/ARBs after ischemic stroke in patients with hypertension is associated with a reduced risk of PSE, especially among younger patients.

Angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin receptor blockers (ARBs) are not recommended during the second and third trimester because of the significant risk of congenital anomalies associated with their use. However, data are scarce, especially regarding their use in the first trimester and about the impact of stopping just before pregnancy. Our study illustrates the profile of the women who used ACE-Is or ARBs during pregnancy and evaluates the impact on perinatal outcomes. The Registry of Pregnancy and Cardiac Disease is a prospective, global registry of pregnancies in women with structural heart disease. Outcomes were compared between women who used ACE-Is or ARBs and those who did not. Multivariable regression analysis was performed to assess the effect of ACE-I or ARB use on the occurrence of congenital anomalies. ACE-Is (n = 35) and/or ARBs (n = 8) were used in 42 (0.7%) of the 5,739 Registry of Pregnancy and Cardiac Disease pregnancies. Women who used ACE-Is or ARBs more often came from a low-or-middle-income country (57% vs 40%, p = 0.021), had chronic hypertension (31% vs 6%, p <0.001), or a left ventricular ejection fraction <40% (33% vs 4%, p <0.001). In the multivariable analysis, ACE-I use during the first trimester was associated with an increased risk of congenital anomaly (odds ratio 3.2, 95% confidence interval 1.0 to 9.6). Therefore, ACE-Is should be avoided during pregnancy, also in the first trimester, because of a higher risk of congenital anomalies. However, there is no need to stop long before pregnancy. Preconception counseling is crucial to discuss the potential risks of these medications, to evaluate the clinical condition and, if possible, to change or stop the medication.

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.

Endometriosis is a chronic inflammatory disorder described by the presence of functional endometrial-like tissues at extra-uterine locations that are related to chronic pelvic pain and infertility. Multiple molecular mechanisms, including inflammation, reactive oxygen species (ROS) generation, fibrotic reactions, and angiogenesis, are involved in the pathogenesis of endometriosis; however, the exact cause of this disorder still remains a matter of discussion. Recently, it has been shown that the local renin-angiotensin system (RAS) has been expressed in different tissues, like the gynecological tract, and alterations in its expression are associated with multiple pathological conditions like endometriosis. Angiotensin II (Ang II), as a main peptide of the RAS through angiotensin type 1 receptor (AT1R), upregulates signal transduction pathways such as nuclear factor kappa B (NF-κB), mitogen activation protein kinase (MAPK), and transforming growth factor beta (TGF-β) to promote inflammation, oxidative stress, and fibrogenesis. Angiotensin receptor blockers (ARBs) control high blood pressure, which is increased by excessive AT1R activity. Recently, it has been recognized that ARBs have tissue protective effects because of their anti-inflammatory and antifibrotic effects. In this review, we focused on the role of local Ang II/AT1R axis activity in endometriosis pathogenesis and justified the use of ARB agents as a potential therapeutic strategy to improve endometriosis.

BACKGROUND: The standard treatment for Kawasaki disease is immunoglobulin therapy, but the high frequency of coronary sequelae in immunoglobulin-refractory cases indicates a need for further improvement in treatment.
METHODS: Kawasaki disease-like vasculitis was induced in 5-week-old DBA/2 mice by intraperitoneal administration of 0.5 mg Candida albicans water-soluble fraction (CAWS) daily for 5 days followed by daily administration of candesartan, an angiotensin receptor blocker. The vasculitis suppression effect was confirmed histologically and serologically in mice sacrificed at 28 days after the start of candesartan.
RESULTS: The area of inflammatory cell infiltration at the aortic root was 2.4±1.4% in the Control group, 18.1±1.9% in the CAWS group, and 7.1±2.3%, 5.8±1.4%, 7.6±2.4%, and 7.9±5.0% in the CAWS+candesartan 0.125-mg/kg, 0.25-mg/kg, 0.5-mg/kg, and 1.0-mg/kg groups, respectively (p=0.0200, p=0.0122, p=0.0122, and p=0.0200 vs. CAWS, respectively). The low-dose candesartan group also showed significantly reduced inflammatory cell infiltration. A similar trend was confirmed by immunostaining of macrophages and TGFβ receptors. Measurement of the inflammatory cytokines IL-1β, IL-6, and TNF-α confirmed the anti-vasculitis effect of candesartan.
CONCLUSIONS: Candesartan inhibited vasculitis even at clinical doses used in children, making it a strong future candidate as an additional treatment for immunoglobulin-refractory Kawasaki disease.

[This corrects the article DOI: 10.3389/fphar.2023.1291900.].

Cancer therapy-related cardiac dysfunction (CTRCD) is a complication of selected cancer therapy agents associated with decline in left ventricular ejection fraction (LVEF). Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) have established benefits in heart failure with reduced ejection fraction, but their efficacy for preventing CTRCD remains controversial. This narrative systematic review assessed the efficacy and safety of ACEI/ARB in the prevention of cancer therapy LVEF decline. We systematically searched PubMed, Embase and Cochrane from January 1980 to June 2022. Studies of interest were randomised controlled trials of patients with normal LVEF and active malignancy receiving cancer therapy, randomised to receive either an ACEI or ARB compared with a control group. The outcome was the change in LVEF from baseline to the end of the follow-up period. Death, clinical heart failure and adverse drug reactions were recorded. A total of 3731 search records were screened and 12 studies were included, comprising a total of 1645 participants. Nine studies assessed the prevention of anthracycline-induced LVEF decline, of which five showed a beneficial effect (1%-14% higher LVEF in treated groups), whereas four studies showed no effect. Three studies assessed the prevention of trastuzumab-induced LVEF decline, of which one showed a beneficial effect (4% higher LVEF) in a subset of participants. There are mixed data regarding the efficacy of ACEI/ARB in preventing the LVEF decline in patients undergoing anthracycline or trastuzumab therapy, with evidence suggesting no clinically meaningful benefit observed in recent studies.

暂无摘要。

Heart failure with preserved ejection fraction (HFpEF) results from a complex interplay of age, genetic, cardiac remodeling, and concomitant comorbidities including hypertension, obesity, diabetes, and chronic kidney disease (CKD). Renal failure is an important comorbidity of HFpEF, as well as a major pathophysiological mechanism for those patients at risk of developing HFpEF. Heart failure (HF) and CKD are intertwined conditions sharing common disease pathways; the so-called \"kidney tamponade\", explained by an increase in intracapsular pressure caused by fluid retention, is only the latest model to explain renal injury in HF. Recognizing the different phenotypes of HFpEF remains a real challenge; the pathophysiological mechanisms of renal dysfunction may differ across the HF spectrum, as well as the prognostic role. A better understanding of the role of cardiorenal interactions in patients with HF in terms of symptom status, disease progression, and prognosis remains essential in HF management. Historically, patients with HF and CKD have been scarcely represented in clinical trial populations. Current concerns affect the practical approach to HF treatment, and, in this context, physicians are frequently hesitant to prescribe and titrate both new and old treatments. Therefore, the extensive application of HF drugs in diverse HF subtypes with numerous comorbidities and different renal dysfunction etiologies remains a controversial matter of discussion. Numerous recently introduced drugs, such as sodium-glucose-linked transporter 2 inhibitors (SGLT2i), constitute a new therapeutic option for patients with HF and CKD. Because of their protective vascular and hormonal actions, the use of these agents may be safely extended to patients with renal dysfunction in the long term. The present review delves into the phenotype of patients with HFpEF and CKD from a pathophysiological perspective, proposing a treatment approach that suggests a practical stepwise algorithm for the proper application of life-saving therapies in clinical practice.

Many patients undergoing surgical procedures have a history of hypertension, diabetes mellitus, heart failure, or a combination. Often, these conditions involve the chronic use of a renin-angiotensin system inhibitor, including angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs). Observational studies have suggested that continuing ACEIs/ARBs before major noncardiac surgery can increase the risk of intraoperative hypotension, which might drive postoperative complications such as acute kidney injury, myocardial injury, or stroke. Strong recommendations on how to manage ACEIs/ARBs before surgery are, however, lacking owing to insufficient evidence, mostly limited to data from observational studies. Recently, the SPACE trial investigated the impact of preoperative management of ACEIs/ARBs on postoperative myocardial injury. Myocardial injury occurred in 48.3% patients randomised to discontinue and 41.3% patients randomised to continue ACEI/ARB (odds ratio for continuing: 0.77, 95% confidence interval 0.45-1.31). Patients randomised to the \'Stop\' group experienced more postoperative hypertension. In a post hoc analysis, patients randomised to the \'Continue\' group with low preoperative NT-proBNP concentrations (<100 pg ml-1) experienced less myocardial injury after surgery than the \'Stop\' group, whereas no significant difference was observed in patients with elevated preoperative NT-proBNP concentrations. The SPACE trial provides important and new reassuring data on the safety of continuing ACEIs/ARBs before major surgery, challenging previous beliefs.