Impact of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers on the mortality in sepsis: A meta-analysis

BACKGROUND The effect of angiotensin-converting enzyme inhibitors(ACEIs)or angiotensin receptor blockers(ARBs)on the mortality of patients with sepsis is not well characterized.AIM To elucidate the association between prior ACEI or ARB exposure and mortality in sepsis.METHODS The PubMed,EMBASE,Web of Science,and Cochrane Library databases were searched for all studies of premorbid ACEI or ARB use and sepsis mortality until November 302019.Two reviewers independently assessed,selected,and ab-stracted data from studies reporting ACEIs or ARBs,sepsis,and mortality.The primary extracted data consisted of premorbid ACEI or ARB exposure,mortality,and general patient data.Two reviewers independently assessed the risk of bias and quality of evidence.RESULTS A total of six studies comprising 281238 patients with sepsis,including 49799 cases with premorbid ACEI or ARB exposure were eligible for analysis.Pre-morbid ACEIs or ARBs exposure decreased the 30-d mortality in patients with sepsis.Moreover,the use of ACEIs or ARBs was associated with approximately a 6%decreased risk of 30-d mortality.CONCLUSION The results of this systematic review suggest that ACEI or ARB exposure prior to sepsis may be associated with reduced mortality.Further high-quality cohort studies and molecular mechanism experiments are required to confirm our results.

Role of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in cryoballoon ablation outcomes for paroxysmal atrial fibrillation

BACKGROUND Cryoballoon ablation(CBA)is recommended for patients with paroxysmal atrial fibrillation(AF)refractory to antiarrhythmic drugs.However,only 80%of patients benefit from initial CBA.There is growing evidence that pretreatment with angiotensin-converting enzyme inhibitors(ACEIs)and angiotensin receptor blockers(ARBs)decreases the recurrence of AF postablation,particularly in nonparoxysmal AF undergoing radiofrequency ablation.The role of ACEIs and ARBs in patients with paroxysmal AF in CBA remains unknown.We decided to investigate the role of ACEIs and ARBs in preventing the recurrence of atrial arrhythmia(AA)following CBA for paroxysmal AF.AIM To investigate the role of ACEIs and ARBs in preventing recurrence of AA following CBA for paroxysmal AF.METHODS We followed 103 patients(age 60.6±9.1 years,29%women)with paroxysmal AF undergoing CBA 1-year post procedure.Recurrence was assessed by documented AA on electrocardiogram or any form of long-term cardiac rhythm monitoring.A multivariable Cox proportional hazard model was used to assess if ACEI or ARB treatment predicted the risk of AA recurrence.RESULTS After a 1-year follow-up,19(18.4%)participants developed recurrence of AA.Use of ACEI or ARB therapy was noted in the study population.Patients on ACEI/ARB had a greater prevalence of hypertension and coronary artery disease.On a multivariate model adjusted for baseline demographics and risk factors for AF,ACEI or ARB therapy did not prevent recurrence of AA following CBA(P=0.72).Similarly,on Kaplan–Meier analysis pretreatment with ACEI/ARB did not predict the time to first recurrence of AA(P=0.2173).CONCLUSION In our study population,preablation treatment with an ACEI or ARB had no influence on the recurrence of AA following CBA for paroxysmal AF.

Angiotensin receptor blocker neprilysin inhibitors

Heart failure(HF)is a clinical syndrome that results from a structural or functional cardiac disorder that reduces the ability of the ventricle of the heart to fill with,or eject,blood.It is a multifaceted clinical condition that affects up to 2%of the population in the developed world,and is linked to significant morbidity and mortality;it is therefore considered a major concern for public health.Regarding the mechanism of HF,three neurohumoral factors-the reninangiotensin-aldosterone system,the sympathetic nervous system,and natriuretic peptides—are related to the pathology of chronic HF(CHF),and the targets of treatment.Angiotensin receptor blocker and neprilysin inhibitor(angiotensinreceptor neprilysin inhibitor),namely sacubitril/valsartan(SAC/VAL),has been introduced as a treatment for CHF.SAC/VAL is an efficacious,safe,and costeffective therapy that improves quality of life and longevity in patients with HF with reduced ejection fraction(HFrEF),and reduces hospital admissions.An inhospital initiation strategy offers a potential new avenue to improve the clinical uptake of SAC/VAL.In the last five years,SAC/VAL has been established as a cornerstone component of comprehensive disease-modifying medical therapy in the management of chronic HFrEF.On the other hand,further work,with carefully designed and controlled preclinical studies,is necessary for understanding the molecular mechanisms,effects,and confirmation of issues such as long-term safety in both human and animal models.

Hyperkalemia of Angiotensin-converting Enzyme Inhibitors or Angiotensin Receptor Blockers in Hemodialysis: A Meta-analysis

The safety of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) used in hemodialysis (HD) patients was evaluated.Medline,Embase,the Cochrane Library,some databases of clinical trial registries,grey literatures,other reference lists of eligible articles and review articles for the randomized clinical trials (RCTs) on comparison of ACEIs/ARBs or placebo in HD patients were retrieved.RCTs reporting the risk of hyperkalemia by using ACEIs/ARBs in HD patients were selected.Eight articles met the eligibility criteria and were subjected to meta-analysis by using the Cochrane Collaboration’s RevMan 4.2 software package.The results showed that there was no significant difference in hyperkalemia in HD patients between ACEIs or ARBs group and control group (ACEIs vs.control:RD=0.03,95% CI=-0.13?0.18,Z=0.34,P=0.73;ARBs vs.control:RD=-0.02,95% CI=-0.07?0.03,Z=0.75,P=0.45).However,there was no significant difference in the serum potassium between ACEIs or ARBs group and control group in HD patients (ACEIs vs.control:WMD=0.10,95% CI=0.06?0.15,Z=4.64,P<0.00001;ARBs vs.control:WMD=-0.24,95% CI=-0.37--0.11,Z=3.58,P=0.0003).The use of ACEIs or ARBs could not cause an increased risk of hyperkalemia in HD patients,however the serum potassium could be increased with use of ACEIs in HD patients.Therefore the serum potassium concentration should still be closely monitored when ACEIs are taken during the maintenance HD.

Angiotensin converting enzymes inhibitors or angiotensin receptor blockers should be continued in COVID-19 patients with hypertension

BACKGROUND Recent studies have revealed that sustained ingestion of angiotensin converting enzymes inhibitors or angiotensin receptor blockers(ACEIs/ARBs)had no harmful effects on coronavirus disease 2019(COVID-19)patients complicated with hypertension.AIM To investigate the impact on COVID-19 patients complicated with hypertension who discontinued using ACEIs/ARBs.METHODS All COVID-19 patients complicated with hypertension admitted to our isolated unit were consecutively recruited in this study.Some patients switched from ACEIs/ARBs to calcium channel blocker(CCBs)after admission,while others continued using non-ACEIs/ARBs.We compared characteristics and clinical outcomes between these two groups of patients.RESULTS A total of 53 patients were enrolled,27 patients switched from ACEIs/ARBs to CCBs while 26 patients continued with non-ACEIs/ARBs.After controlling potential confounding factors using the Cox proportional hazards model,hospital stay was longer in patients who discontinued ACEIs/ARBs,with a hazard ratio of 0.424(95%confidence interval:0.187-0.962;P=0.040),upon discharge than patients using other anti-hypertensive drugs.A sub-group analysis showed that the effect of discontinuing use of ACEIs/ARBs was stronger in moderate cases[hazard ratio=0.224(95%confidence interval:0.005-0.998;P=0.0497)].CONCLUSION Patients in the discontinued ACEIs/ARBs group had longer hospital stays.Our findings suggest that COVID-19 patients complicated with hypertension should continue to use ACEIs/ARBs.

Effects of angiotensin receptor blockers and angiotensin-converting enzyme inhibitors on COVID-19

BACKGROUND The World Health Organization reported that 28637952 people worldwide had been infected with severe acute respiratory syndrome coronavirus 2,the causative agent of coronavirus disease 2019(COVID-19),by September 13.AIM The aim was to investigate whether long-term use of renin-angiotensin-aldosterone system(RAAS)inhibitors for the treatment of hypertension aggravates the performance of COVID-19 patients with hypertension.METHODS This was a retrospective analysis of lung computed tomography(CT)data and laboratory values of COVID-19 patients with hypertension who were admitted to Huoshenshan Hospital,Wuhan,Hubei Province,between February 18 and March 31,2020.Patients were divided into two groups.Group A included 19 people who were long-term users of RAAS inhibitors for hypertension;and group B included 28 people who were randomly selected from the database and matched with group A by age,sex,basic diseases,and long-term use of other antihypertensive drugs.All patients underwent a series of CT and laboratory tests.We compared the most severe CT images of the two groups and the laboratory examination results within 2 d of the corresponding CT images.RESULTS The time until the most severe CT images from the onset of COVID-19 was 30.37±14.25 d group A and 26.50±11.97 d in group B.The difference between the two groups was not significant(t=1.01,P=0.32).There were no significant differences in blood laboratory values,C-reactive protein,markers of cardiac injury,liver function,or kidney function between the two groups.There was no significant difference in the appearance of the CT images between the two groups.The semiquantitative scores of each involved lobe were 11.84±5.88 in group A and 10.36±6.04 group B.The difference was not significantly different(t=0.84,P=0.41).CONCLUSION Chest CT is an important imaging tool to monitor the characteristics of COVID-19 and the degree of lung injury.Chronic use of RAAS inhibitors is not related to the severity of COVID-19,and it does not worsen the clinical process.

Angiotensin receptor blocker drugs and inhibition of adrenal beta-arrestin-1-dependent aldosterone production: Implications for heart failure therapy

Aldosterone mediates many of the physiological and pathophysiological/cardio-toxic effects of angiotensin II(Ang II). Its synthesis and secretion from the zona glomerulosa cells of the adrenal cortex, elevated in chronic heart failure(HF), is induced by Ang II type 1 receptors(AT1Rs). The AT1R is a G protein-coupled receptor, mainly coupling to Gq/11 proteins. However, it can also signal through β-arrestin-1(βarr1) or-2(βarr2), both of which mediate G protein-independent signaling. Over the past decade, a second, Gq/11 proteinindependent but βarr1-dependent signaling pathway emanating from the adrenocortical AT1R and leading to aldosterone production has become appreciated. Thus, it became apparent that AT1R antagonists that block both pathways equally well are warranted for fully effective aldosterone suppression in HF. This spurred the comparison of all of the currently marketed angiotensin receptor blockers(ARBs, AT1R antagonists or sartans) at blocking activation of the two signaling modes(G protein-, and βarr1-dependent) at the Ang IIactivated AT1R and hence, at suppression of aldosterone in vitro and in vivo. Although all agents are very potent inhibitors of G protein activation at the AT1R, candesartan and valsartan were uncovered to be the most potent ARBs at blocking βarr activation by Ang II and at suppressing aldosterone in vitro and in vivo in post-myocardial infarction HF animals. In contrast, irbesartan and losartan are virtually G protein-"biased" blockers at the human AT1R, with very low efficacy for βarr inhibition and aldosterone suppression. Therefore, candesartan and valsartan(and other, structurally similar compounds) may be the most preferred ARB agents for HF pharmacotherapy, as well as for treatment of other conditions characterized by elevated aldosterone.

Network Meta-analysis of Four Chinese Patent Medicines Combined with Angiotensin Converting Enzyme Inhibitors or Angiotensin Receptor Blockers in Early Diabetic Nephropathy Treatment

The objective of the study is to systematically evaluate the efficacy of four Chinese patent medicines in combination with angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARB) in the treatment of early diabetic nephropathy (DN). Retrospectively, previously published randomized controlled trials (RCTs) of four different Chinese patent medicines combined with ACEI or ARB in the treatment of patients with early DN were searched overall from databases. The data were analyzed by R, Generate Mixed Treatment Comparisons and STATA softwares. A total of 78 RCTs were finally included. Network meta-analysis showed that the total effective rate of the Jinshuibao capsule-ACEI/ARB combination group and Huangkui capsule-ACEI/ARB combination groups were better than the others;Jinshuibao capsule-ACEI/ARB combination group reduced the 24-h urinary protein excretion (24-h UTP), urine microalbumin excretion rate (UAER), serum creatinine (Scr), and glycosylated hemoglobin (HbAlc) values. The Huangkui capsule-ACEI/ARB combination demonstrated a better reduction of (blood urea nitrogen [BUN]). Reduced incidences of adverse effects were only observed on treatment with Bailing capsule-ACEI/ARB combination. In early DN, combination of Jinshuibao capsule-ACEI/ARB provided the highest effective rate;moreover, it could reduce the24-h values of UTP, UAER, Scr, and HbAlc;Huangkuai capsule-ACI/ARB combination group showed a good effect on reducing BUN. Bailing capsule-ACEI/ARB combination group had reduced the incidences of adverse reactions.

Renoprotection Provided by Dipeptidyl Peptidase-4 Inhibitors in Combination with Angiotensin Receptor Blockers in Patients with Type 2 Diabetic Nephropathy

Background: Treatment with the dipeptidyl peptidase-4 inhibitors (DPP4i) and angiotensin receptor blockers (ARBs) in patients with type 2 diabetic nephropathy (DN) has not been well characterized. This study aimed to assess the renoprotection of this combined treatment in DN patients.Methods: A total of 159 type 2 DN patients from 2013 to 2015 were enrolled retrospectively from a prospective DN cohort at the National Clinical Research Center of Kidney Diseases, Jinling Hospital (China). Fifty-seven patients received DPP4i and ARB treatment, and 102 patients were treated with ARBs alone. All patients were followed up for at least 12 months. Statistical analyses were performed using Stata version 12.0.Results: There were no significant differences at baseline for age, sex, body mass index, duration of diabetes, fasting blood glucose (FBG), hemoglobin A1c (HbA1c), and estimated glomerular filtration rate (eGFR) between the two groups. Antihypertensive and antidiabetic medication use was similar in each group except calcium channel antagonists (P = 0.032). No significant changes in FBG and HbA1c were observed in the two groups after treatment. The eGFR decreased slower in the DPP4i + ARB group than in the ARB group at 12 months (?12 months: -2.48 ± 13.86 vs. -6.81 ± 12.52 ml·min–1·1.73m–2,P = 0.044). In addition, proteinuria was decreased further in the DPP4i + ARB group than in the ARB group after 24 months of treatment (?24 months: -0.18 [-1.00, 0.17] vs. 0.32 [-0.35, 0.88],P = 0.031). There were 36 patients with an eGFR decrease of more than 30% over 24 months. After adjusting for FBG, HbA1c, and other risk factors, DPP4i + ARB treatment was still associated with a reduced incidence of an eGFR decrease of 20% or 30%.Conclusions: The combined treatment of DPP4i and ARBs is superior to ARBs alone, as evidenced by the greater proteinuria reduction and lower eGFR decline. In addition, the renoprotection of DPP4i combined with ARBs was independent of glycemic control.

Use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers increases the risk of postoperative acute kidney injury after elective endovascular abdominal aortic aneurysm repair

Background: Endovascular abdominal aortic aneurysm repair (EVAR) is the major treatment for abdominal aortic aneurysm (AAA);however, EVAR still carries a considerable risk of acute kidney injury (AKI). The present study aimed to investigate the risk factors for AKI after elective EVAR procedures.Methods: This was a retrospective observational study. Eligible patients who underwent EVAR from September 2011 to March 2019 in West China Hospital were included. The primary outcome was the occurrence of AKI within two days after EVAR, which was defined by the Kidney Disease Improving Global Outcomes Clinical Practice Guideline. Demographics, comorbidities, medications, laboratory tests, anatomical parameters of AAA, and relative operative details were collected as variables. Univariable and multivariable logistic regression analyses were applied to identify the risk factors among variables, and covariate interactions were further assessed.Results: A total of 679 eligible patients were included. The incidence of postoperative AKI was 8.2% (56/679) in the whole cohort, and it was associated with a lower 5-year survival rate (63.5%vs. 80.9%;χ^(2) = 4.10;P = 0.043). The multivariable logistic regression showed that chronic kidney disease (OR, 5.06;95% CI: 1.43-17.95;P = 0.012), angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) (OR, 2.60;95% CI: 1.17-5.76;P = 0.019), and short neck (OR, 2.85;95% CI: 1.08-7.52;P = 0.035) were independent risk factors for postoperative AKI. In the covariate interaction analysis, the effect of ACEIs/ARBs use on postoperative AKI was similar across all subgroups (P > 0.05), thereby suggesting a robust effect of ACEIs/ARBs use in all patients undergoing elective endovascular abdominal aortic aneurysm repair.Conclusions: Postoperative AKI was associated with lower survival rate, and the use of ACEIs/ARBs was the only adjustable independent risk factor. Clinicians should consider withdrawing ACEIs/ARBs in high-risk patients undergoing elective endovascular abdominal aortic aneurysm repair to prevent postoperative AKI.

Effect of angiotensin receptor blockers in the prevention of type 2 diabetes and cardiovascular events： a meta-analysis of randomized trials

Background As the incidence of type 2 diabetes is rapidly increasing, prevention of the disease should be considered as a crucial objective in the near future. Several studies have shown angiotensin receptor blockers （ARBs） may contribute to the prevention of new-onset type 2 diabetes. This study was conducted to determine if ARBs as monotherapy or combination therapy may experience a decreased incidence of new-onset type 2 diabetes and prevent cardiovascular events. Methods Relevant experimental and clinical studies were identified by searching MEDLINE （1969 to May 30, 2011） to extract a consensus of trial data involving the effect of ARBs on prevention of new-onset type 2 diabetes and cardiovascular events. Studies were included if they were randomized controlled trials versus placebo/routine therapy. A random-effects model was utilized. Subgroup and sensitivity analyses were conducted. Results Eleven trials were identified, including 82738 patients. ARBs prevented new-onset type 2 diabetes （odds ratio 0.8 （95% CI 0.76, 0.85））. Regardless of indication for use, essential hypertension （seven trials）, impaired glucose tolerance （one trial）, cardiocerebrovascular disease （two trials） or heart failure （one trial）, reductions in new-onset type 2 diabetes were maintained （0.75 （0.69, 0.82）, 0.85 （0.78, 0.92）, 0.80 （0.76, 0.85） and 0.80 （0.64, 0.99）, respectively）. No statistical heterogeneity was observed for any evaluation. However, ARBs did not significantly reduce the odds of all-cause mortality, myocardial infarction and heart failure versus control therapy among all of these studies. But ARBs did reduce the odds of cardiac death and heart failure among the heart failure study versus control therapy. Conclusion ARBs have significant ability to reduce risk of developing new-onset type 2 diabetes but does not improve cardiovascular outcomes over the study follow-up periods among all of included studies.

Retrospective analysis of the prognostic effect of angiotensin receptor blocker on non-Marfan aortic dissection

Background Aortic dissection(AD)is a life-threatening vascular disease caused by various etiologies including Marfan’s syndrome.Angiotensin receptor blocker(ARB)drugs have been confirmed beneficial for patients with Marfanoid AD but remain unclear for non-Marfanoid case.Methods Patients with DeBakey typeⅢ,Standford A aortic dissection were consecutively recruited to Guangdong Provincial People’s Hospital and Jieyang People’s Hospital between January 2010 and January 2015,with 25 individuals in the ARB group and 32 individuals in the non-ARB group(control group),respectively.The follow-up was performed by database or telephone.The follow-up data consisted of patient’s symptoms and chief complaints,blood pressure,heart rate,and aortic computed tomography angiography(CTA)data.Endpoints and in-hospital events were recorded.Results Baseline data,including age,gender,heart rate,smoking status,and the incidence of diabetes,demonstrated no significant difference between two groups.There was neither death nor urgent surgical case in either group during the follow-up period.The aortic CTA follow-up demonstrated the absorption of the proximal inversely avulsed hematoma for both groups,whereas the reduction was more evident in the ARB group as compared with the non-ARB group[-(9.33±1.99)mm vs.-(4.08±2.35)mm,respectively,P<0.05],suggesting that hematoma absorption was more remarkable in the ARB group.The maximum vascular diameter at the dissection in both groups declined during the follow-up,whereas the reduction in the ARB group was significantly more striking relative to that in the non-ARB group[-(5.50±1.15)mm vs.-(0.31±0.69)mm,respectively,P<0.001],indicating a potential role of ARB drugs in curbing aortic enlargement and remodeling.Conclusions Independent of blood pressure(BP)reduction,ARB utilization in patients with non-Marfan’s aortic dissection may facilitate the absorption of reverse-torn hematoma at the proximal end of dissection,as well as delaying the aortic dilation and remodeling.

Effect of angiotensin Ⅱ type 1 receptor blocker and angiotensin converting enzyme inhibitor on the intraocular growth factors and their receptors in streptozotocin-induced diabetic rats

AIM： To investigate the effect of angiotensin II type 1 receptor blocker （ARB） and angiotensin converting enzyme inhibitor （ACEI） on intraocular growth factors and their receptors in streptozotocin-induced diabetic rats. METHODS： Forty Sprague-Dawley rats were divided into 4 groups： control, diabetes mellitus （DM）, candesartan- treated DM, and enalapril-treated DM （each group, n---10）. After the induction of DM by streptozotocin, candesartan [ARB, 5 mg/（kg · d）] and enalapril [ACEI, 10 mg/（kg · d）] were administered to rats orally for 4Wko Vascular endothelial growth factor （VEGF） and angiotensin II （Ang II） concentrations in the vitreous were measured using enzyme-linked immunosorbent assays, and VEGF receptor 2 and angiotensin II type 1 receptor （ATIR） levels were assessed at week 4 by Western blotting. RESULTS： Vitreous Ang II levels were significantly higher in the DM group and candesartan-treated DM group than in the control （P=0.04 and 0.005, respectively）. Vitreous ATIR increased significantly in DM compared to the other three groups （P〈0.007）. Candesartan-treated DM rats showed higher vitreal ATIR concentration than the enalapril-treated DM group and control （P〈0.001 and P=0.005, respectively）. No difference in vitreous Ang II and ATIR concentration was found between the enalapril- treated DM group and control. VEGF and its receptor were below the minimum detection limit in all 4 groups. CONCLUSION： Increased Ang II and ATIR in the hyperglycemic state indicate activated the intraocular renin-angiotensin system, which is inhibited more effectively by systemic ACEI than systemic ARB.

Effects of angiotensin-converting enzyme inhibitor and angiotensin Ⅱ receptor blocker on one-year outcomes of patients with atrial fibrillation: insights from a multicenter registry study in China

Objective To evaluate the effect of angiotensin-converting enzyme inhibitor(ACEI)/angiotensin Ⅱ receptor blocker(ARB)therapy on the prognosis of patients with atrial fibrillation(AF).Methods A total of 1,991 AF patients from the AF registry were divided into two groups according to whether they were treated with ACEI/ARB at recruitment.Baseline characteristics were carefully collected and analyzed.Logistic regression was utilized to identify the predictors of ACEI/ARB therapy.The primary endpoint was all-cause mortality,while the secondary endpoints included cardiovascular mortality,stroke and major adverse events(MAEs)during the one-year follow-up period.Univariable and multivariable Cox regression were performed to identify the association between ACEI/ARB therapy and the one-year outcomes.Results In total,759 AF patients(38.1%)were treated with ACEI/ARB.Compared with AF patients without ACEI/ARB therapy,patients treated with ACEI/ARB tended to be older and had a higher rate of permanent AF,hypertension,diabetes mellitus,heart failure(HF),left ventricular ejection fraction(LVEF)<40%,coronary artery disease(CAD),prior myocardial infarction(MI),left ventricular hypertrophy,tobacco use and concomitant medications(all P<0.05).Hypertension,HF,LVEF<40%,CAD,prior MI and tobacco use were determined to be predictors of ACEI/ARB treatment.Multivariable analysis showed that ACEI/ARB therapy was associated with a significantly lower risk of one-year all-cause mortality[hazard ratio(HR)(95%CI):0.682(0.527-0.882),P=0.003],cardiovascular mortality[HR(95%CI):0.713(0.514-0.988),P=0.042]and MAEs[HR(95%CI):0.698(0.568-0.859),P=0.001].The association between ACEI/ARB therapy and reduced mortality was consistent in the subgroup analysis.Conclusions In patients with AF,ACEI/ARB was related to significantly reduced one-year all-cause mortality,cardiovascular mortality and MAEs despite the high burden of cardiovascular comorbidities.

The Significance of Angiotensin Converting Enzyme Inhibitor or Angiotensin II Receptor Blocker Use in Sudden Cardiac Death

Objectives: To investigate the relationship between the use of angiotensin converting enzyme (ACE) inhibitor or angiotensin II receptor blocker (ARB) and hyperkalemia in patients diagnosed with sudden cardiac death. Methods: We examined oral ACE inhibitor or ARB use among cardiopulmonary arrest patients brought by ambulance to our emergency room during a 5-year period from January 2012 to December 2016. The cause of death was determined to be sudden cardiac death, despite temporary return of spontaneous circulation after starting cardiopulmonary resuscitation. Subjects were dichotomized into 2 groups, those taking and those not taking an ACE inhibitor or ARB. Variables determined retrospectively included serum potassium, estimated glomerular filtration rate as an index of kidney function and time from cardiopulmonary arrest to return of spontaneous circulation. The Mann-Whitney U-test was used to compare continuous data, and the chi-square test to compare categorical data between groups. The results are expressed as the median plus range. Statistical significance was assumed at p Results: Thirty-five patients met the inclusion criteria. The mean age was 77.1 years (range, 35 - 93 years), and there were 26 males and 9 females. Eleven subjects were ACE inhibitor or ARB users, and 24 were non-users. The serum potassium level was significantly higher in users than non-users (median, 6.2 mEq/L (range, 4.5 - 10.0) vs. 5.2 mEq/L (range, 3.6 - 8.3);p = 0.001). The estimated glomerular filtration rate was significantly lower in users than non-users (median, 25.1 mL/min/1.73 m2 (range, 4.6 - 60.3) vs. 46.9 mL/min/1.73 m2 (range, 19.8 - 97.1);p = 0.009). There was no significant difference in time from cardiopulmonary arrest to return of spontaneous circulation between the 2 groups (median, 24 minutes (range, 3 - 111) vs. 29 minutes (range, 10 - 54);p = 0.355). Conclusion: It is possible that hyperkalemia induced by ACE inhibitor or ARB use is a cause of sudden cardiac death, especially in patients with chronic kidney disease.

厄贝沙坦通过调节NLRP3表达在糖尿病肾病大鼠中的保护作用

目的 观察糖尿病肾病大鼠中NLRP3(NOD-like receptor protein 3)的表达,并在沉默NLRP3和以血管紧张素受体抑制剂(ARB)厄贝沙坦干预后观察NLRP3及炎症和纤维化因子的表达变化,探讨厄贝沙坦对糖尿病肾病大鼠的保护作用。方法 雄性SD大鼠随机分成5组:对照(Control)组、模型(Model)组、空载(Model+Blank)组、NLRP3沉默(Model+NLRP3 Sh)组、ARB(Model+ARB)组,分别在糖尿病肾病模型建立后8周、12周处死大鼠并收集肾脏组织。实时荧光定量PCR检测NLRP3、半胱氨酸天冬氨酸蛋白酶-1(Caspase-1)、核因子κB(NF-κB)P65和波形蛋白(Vimentin)的mRNA表达水平;Western blot检测NLRP3、P65、热休克蛋白47(heat shock protein 47,HSP47)和Vimentin的蛋白表达水平;免疫荧光法观察NLRP3、Caspase-1和Vimentin的表达;PAS、PASM和Masson染色观察肾脏病理改变。结果 与对照组比较,模型组及空载组NLRP3、Caspase-1、P65和Vimentin mRNA的表达升高(均P<0.05),NLRP3、Caspase-1、P65、HSP47和Vimentin的蛋白表达升高(均P<0.05)。与模型组及空载组相比,NLRP3沉默组及ARB组的上述指标表达均下调(均P<0.05),模型组与空载组以上指标之间差异无统计学意义。病理染色结果显示NLRP3沉默和厄贝沙坦干预可减轻糖尿病肾病大鼠肾脏损害,减轻肾小球肥大、肾小球硬化、系膜扩张、间质纤维化。结论 糖尿病肾病大鼠肾脏NLRP3信号通路被激活,且炎性和纤维化因子表达上调。厄贝沙坦可阻断NLRP3信号通路,减轻肾脏损害。天然免疫受体NLRP3可能成为治疗糖尿病肾病的新靶点。

Immunoglobulin A glomerulonephropathy:A review

In this editorial,we comment on the article by Meng et al published in the World Journal of Clinical Cases.We comprehensively review immunoglobulin A nephro-pathy(IgAN),including epidemiology,clinical presentation,diagnosis,and management.IgAN,also known as Berger's disease,is the most frequent type of primary glomerulonephritis(GN)globally.It is mostly found among the Asian population.The presentation can be variable,from microscopic hematuria to a rapidly progressive GN.Around 50%of patients present with single or recurring episodes of gross hematuria.An upper respiratory infection and tonsillitis often precede these episodes.Around 30%of patients present microscopic hematuria with or without proteinuria,usually detected on routine examination.The diagnosis relies on having a renal biopsy for pathology and immunofluorescence microscopy.We focus on risk stratification and management of IgAN.We provide a review of all the landmark studies to date.According to the 2021 KDIGO(kidney disease:Improving Global Outcomes)guidelines,patients with non-variant form IgAN are first treated conservatively for three to six months.This approach consists of adequate blood pressure control,reduction of proteinuria with renin-angiotensin system blockade,treatment of dyslipidemia,and lifestyle modifications(weight loss,exercise,smoking cessation,and dietary sodium restrictions).Following three to six months of conservative therapy,patients are further classified as high or low risk for disease progression.High-risk patients have proteinuria≥1 g/d or<1 g/d with significant microscopic hematuria and active inflammation on kidney biopsy.Some experts consider proteinuria≥2 g/d to be very high risk.Patients with high and very high-risk profiles are treated with immunosuppressive therapy.A proteinuria level of<1 g/d and stable/im-proved renal function indicates a good treatment response for patients on immu-nosuppressive therapy.

沙库巴曲缬沙坦治疗消融术后心房颤动的疗效及安全性的Meta分析

目的系统评价沙库巴曲缬沙坦(sacubitril/valsartan,SV)治疗心房颤动(atrial fibrillation,AF)的疗效及安全性。方法计算机检索中国知网、万方、维普、PubMed、Embase、Web of Science、The Cochrane Library数据库,检索时限为建库起至2024年4月27日。由两名研究人员独立进行文献筛选、资料提取与质量评价,采用RevMan 5.4软件进行Meta分析。结果共纳入10项研究,包括8项随机对照试验,2项队列研究,共计1355例患者。试验组予以常规治疗+SV,对照组予以常规治疗或常规治疗+血管紧张素转化酶抑制剂(ACEI)/血管紧张素受体拮抗剂(ARB)。Meta分析结果显示,在接受导管射频消融术后转为窦性心律的AF患者中,与常规治疗或常规治疗+ACEI/ARB相比,常规治疗+SV能显著减少AF复发率[OR=0.35,95%CI(0.26,0.46),P<0.001],降低左心房内径[MD=-3.26,95%CI(-4.81,-1.70),P<0.001]与左心房容积指数[MD=-6.50,95%CI(-8.76,-4.25),P<0.001],提高左心室射血分数[MD=3.79,95%CI(2.17,5.41),P<0.001],降低N末端脑钠肽前体水平[MD=-106.49,95%CI(-134.71,-78.27),P<0.001],减少药物不良反应发生率[OR=0.48,95%CI(0.26,0.86),P=0.01],然而在降低血压方面两组疗效相似。结论AF患者导管消融术后应用常规治疗+SV在减少AF复发率、改善左心功能方面相较于常规治疗或常规治疗+ACEI/ARB效果更优,但在降低血压幅度方面两组无明显差异,但此结论还有待更多的高质量研究加以论证。

ACEI和ARB治疗COVID-19合并高血压患者的效果分析

目的血管紧张素转换酶抑制剂(ACEI)和血管紧张素Ⅱ受体阻滞剂(ARB)治疗是否有利于合并高血压的新型冠状病毒感染(COVID-19)患者仍存在争议。该研究旨在探讨ACEI和ARB在COVID-19合并高血压患者中的治疗效果。方法采用回顾性分析方法,选择收治的COVID-19合并高血压患者,根据患者是否使用抗高血压药物ACEI或ARB治疗分为ACEI/ARB组(n=18)和非ACEI/ARB组(n=29),并根据患者的疾病严重程度分为普通型和重型患者,比较分析患者的临床特征、实验室检测结果、影像学数据、临床结局参数等资料。结果所有患者的年龄中位数为65.0岁(57.0~69.0岁),57.4%为男性,76.6%患者有明确的接触史,发病至入院的中位数时间为3.0 d(1.0~7.0 d),比较常见的临床表现为发热(74.5%)、咳嗽(48.9%)、乏力(27.7%)和咳痰(25.5%)。ACEI/ARB组和非ACEI/ARB组的临床分型比较差异无统计学意义(P>0.05),两组患者基线期的临床特征和实验室检查结果的比较均差异无统计学意义(P均>0.05)。在ACEI/ARB组和非ACEI/ARB组中,重型患者的淋巴细胞计数(LYMPH)相对低于普通型患者,乳酸脱氢酶(LDH)、C反应蛋白(CRP)、白细胞介素-6(IL-6)、降钙素原(PCT)和D-二聚体(D-dimer)都普遍高于普通型患者。在病程第15天,非ACEI/ARB组重型患者的LDH、CRP、IL-6、PCT和D-dimer水平均高于ACEI/ARB组的重型患者,但两组间的比较差异无统计学意义(P均>0.05)。非ACEI/ARB组有1例死亡患者,其余患者经过治疗均痊愈出院。所有患者中,ACEI/ARB组的发热持续时间、胸部X线计算机断层扫描(CT)改善时间均短于非ACEI/ARB组,住院时间和病毒核酸转阴时间长于非ACEI/ARB组,但比较均差异无统计学意义(P均>0.05)。普通型患者中,ACEI/ARB组的住院时间、病毒核酸转阴时间和胸部CT改善时间长于非ACEI/ARB组,但仅有病毒核酸转阴时间的比较具差异有统计学意义(P<0.05)。相反地,在重症患者中,非ACEI/ARB组的发热持续时间、住院时间、病毒核酸转阴时间和胸部CT改善时间长于ACEI/ARB组,但差异无统计学意义(P均>0.05)。结论ACEI或ARB治疗可缩短患者发热持续时间,对合并高血压的重症COVID-19患者可能有积极保护作用。