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.

Role of angiotensin converting enzyme and angiotensinogen gene polymorphisms in angiotensin converting enzyme inhibitor-mediated antiproteinuric action in type 2 diabetic nephropathy patients

AIM To investigate the role of genetic variants of angiotensin converting enzyme(ACE) and angiotensinogen(AGT) genes in the antiproteinuric efficacy of ACE inhibitor therapy in diabetic nephropathy(DN) patients.METHODS In the present study, 270 type 2 diabetes mellitus patients with nephropathy were enrolled and treated with ACE inhibitor(ramipril) and followed at 6 mo for renal function and albumin excretion by estimating serum creatinine, end stage renal disease, and albumin/creatinine ratio(ACR) in urine. Genotyping of ACE I/D and AGT M235 T polymorphisms were performed by using primer specific polymerase chain reaction(PCR) and PCR-RFLP techniques, respectively. RESULTS Forty-eight percent of DN patients(responders) benefited with respect to proteinuria from ACE inhibitor therapy at 6 mo follow-up. A significant reduction in ACR was observed after 6 mo treatment with ACE inhibitor irrespective of whether DN patients were micro-albuminuric(≥ 30 and < 300 mg/g creatinine) or macro-albuminuric(≥ 300 mg/g creatinine) at the time of enrollment. However, macro-albuminuric patients(55%) showed better response to therapy. A reduction in urinary ACR was found independent of genotypes of ACE I/D and AGT M235 T polymorphisms although macro-albuminuric patients having TT genotype showed statistically insignificant increased response(72%). CONCLUSION ACE inhibitor therapy reduced urinary ACR by ≥ 30% in 50% of DN patients and the response is independent of ACE I/D and AGT M235 T polymorphisms.

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.

Interferon augments the anti-fibrotic activity of an angiotensin-converting enzyme inhibitor in patients with refractory chronic hepatitis C

AIM: To evaluate the effect of combination treatment with the interferon (IFN) and angiotensin-converting enzyme inhibitor (ACE-Ⅰ) on several fibrotic indices in patients with refractory chronic hepatitis C (CHC). METHODS: Perindopril (an ACE-Ⅰ; 4 mg/d) and/or natural IFN (3 MU/L; 3 times a week) were administered for 12 mo to refractory CHC patients, and several indices of serum fibrosis markers were analyzed. RESULTS: ACE-Ⅰdecreased the serum fibrosis markers, whereas single treatment with IFN did not exert these inhibitory effects. However, IFN significantly augmented the effects of ACE-Ⅰ, and the combination treatment exerted the most potent inhibitory effects. The serum levels of alanine transaminase and HCV-RNA were not significantly different between the groups, whereas the plasma level of transforming growth factor-b was significantly attenuated almost in parallel with suppression of the serum fibrosis markers. CONCLUSION: The combination therapy of an ACE- Ⅰand IFN may have a diverse effect on disease progression in patients with CHC refractory to IFN therapy through its anti-fibrotic effect.

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.

A new angiotensin-converting enzyme inhibitor from Peperomia pellucida(L.) Kunth

Objective:To isolate,identify,and evaluate a new angiotensin-converting enzyme inhibitor from Peperomia pellucida(L.)Kunth herbs.Methods:A dried sample of Peperomia pellucida herb was successively macerated with n-hexane and ethyl acetate.The ethyl acetate extract solution was evaporated to obtain the crude extract.Vacuum liquid column chromatography and thin layer chromatography were performed to obtain two pure compounds.Then,both compounds were elucidated and identified using the spectroscopic method.Angiotensin-converting enzyme inhibitory activity studies of both compounds were determined using angiotensin-converting enzyme kit WST-1 with spectrophotometer microplate reader 96-well at 450 nm wavelength.Results:Two bioactive compounds were successfully isolated from Peperomia pellucida herb,including a new compound of 2,3,5-trimethoxy-9-(12,14,15-trimethoxybenzyl)-1 H-indene and pellucidin A.Both compounds demonstrated angiotensin-converting enzyme inhibitory activity,with IC50 values of 72 μM(27.95 μg/mL)and 1 1μM(4.4 μg/mL),respectively.Conclusions:In the present study,two active angiotensin-converting enzyme inhibitors were successfully isolated and purified from Peperomia pellucida which is used as an antihypertensive in traditional medicine,and support its use as an angiotensin-converting enzyme-inhibiting drug.

Microwave-assisted Solid-phase Synthesis, Biological Evaluation and Molecular Docking of Angiotensin I-converting Enzyme Inhibitors

Short peptides based on the tripeptides, Leu-Arg-Pro and Leu-Lys-Pro, were synthesized by microwave assisted solid-phase synthesis method, in order to make a search for potential inhibitors for angiotensin I-converting enzyme（ACE） with minimum side effects in the treatment of hypertension. One peptide with the sequence Leu-Arg-Pro-Phe-Phe shows the strongest inhibition towards ACE with an IC50 value of 0.26 μmol/L in vitro. The study of structure-activity relationship shows that the introduction of a bulky group into the N-terminal of this series of inhibitors may enlarge steric hindrance, resulting in the poor inhibitory activity towards ACE. The inhibitory activity decreased in turn when L-Pro, D-Pro or Ac6c was at the C-terminal respectively. The binding interaction between each of these inhibitors and testicular ACE（tACE） was performed by molecular docking. The results suggest that Leu-Arg-Pro-Phe-Phe mainly occupied the S1 subsite of tACE, and made contact with tACE via seven H-bonds. It appeared that the site on the peptide that bound with tACE was influenced by the configuration of the amino acid, L or D-form, at the C-terminal of the peptide.

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.

Angiotensin-Converting Enzyme Inhibitor Induced Angioedema Occurring after 8 Years of Taking Lisinopril: A Case Report

Angiotensin-converting enzyme inhibitor induced angioedema (AIIA) can vary from mild to life-threatening. A vast majority of cases of AIIA occur within a month of starting an angiotensin-converting enzyme-inhibitor (ACE-I). We present a 48-year-old male who presented with respiratory failure secondary to AIIA, after being on lisinopril for over 8 years. He had no previous complications secondary to lisinopril and aside from smoking, carried no risk factors for AIIA. Despite conventional treatment for angioedema, he had a prolonged stay in the Medical Intensive Care Unit (MICU). Following discharge, there hasn’t been a recurrence of AIIA since the discontinuation of lisinopril. The case is intended to caution that AIIA remains possible even late into a chronic regimen of ACE-I. This is a risk that shouldn’t be neglected, even with sparse risk factors or longer duration of ACE-I use. Conventional treatment is not currently in line with proposed etiologies of AIIA. We advocate for more clinical trials involving pharmaceutical agents targeting bradykinin accumulation.

Effects of angiotensin converting enzyme inhibitors on cognitive function, apoptosis and oxidative stress in brain tissue of rats with cerebral infarction

Objective:To study the effects of angiotensin converting enzyme inhibitor(ACEI)on cognitive function,apoptosis and oxidative stress in brain tissue of rats with cerebral infarction.Methods:Adult male SD rats were randomly divided into control group,cerebral infarction group and ACEI group.The latter two groups were used to establish cerebral infarction model by thread embolism.The ACEI group was given oral administration of fosinopril 10mg/kg,and the other two groups were given oral administration of saline.The differences of Morris water maze cognitive function,apoptotic genes and oxidative stress indexes were compared among the three groups.Results:The escape latency of rats in cerebral infarction group was significantly longer than that in control group,the number of times of platform crossing was significantly less than that in control group,the duration of platform stay was significantly shorter than that in control group,the mRNA expression levels of Bcl-2 associated X protein(Bax),factor associated suicide(Fas),Fas ligand(FasL)and Caspase-3,the protein expression levels of phosphorylated Janus kinase(p-JAK2)and phosphorylated signal transducer and activator of transcription(p-STAT3)as well as the contents of reactive oxygen species(ROS)and malonaldehyde(MDA)in brain tissue were significantly higher than those in control group,and the mRNA expression level of B-cell lymphoma-2(Bcl-2)as well as the contents of catalase(CAT)and superoxide dismutase(SOD)in brain tissue was significantly lower than those in control group.The escape latency of rats in ACEI group was significantly shorter than that in cerebral infarction group,the number of times of platform crossing was significantly more than that in cerebral infarction group,the duration of platform stay was significantly longer than that in cerebral infarction group,the mRNA expression levels of Bax,Fas,FasL and Caspase-3,the protein expression levels of p-JAK2 and p-STAT3 as well as the contents of ROS and MDA in brain tissue were significantly lower than those in cerebral infarction group,and the mRNA expression level of Bcl-2 as well as the contents of CAT and SOD in brain tissue was significantly higher than those in cerebral infarction group.Conclusions:ACEI can improve the cognitive function of rats with cerebral infarction and inhibit the apoptosis and oxidative stress in ischemic brain tissue.

Angiotensin-converting enzyme and bradykinin gene polymorphisms and cough:A meta-analysis

AIM:To evaluate the association between genetic polymorphisms and angiotensin converting enzyme in-hibitor (ACEI)-related cough,and the race-or ethnicity-related difference in the prevalence of cough attributed to ACEI therapy.METHODS:We conducted a search in PubMed,EM-BASE,Cinahl,and the Cochrane Database without language limitation.A database of 11 studies on ACEI-related cough,with detailed information regarding ACE I/D or bradykinin B 2 receptor polymorphisms,was created.Eligible studies were synthesized using meta-analysis methods,including cumulative meta-analysis.A subgroup analysis was also performed using ethnicity.RESULTS:Six studies were included on ACE I/D poly-morphism (398 Caucasians,723 East Asians),and three studies were included on bradykinin B 2 receptor poly-morphism (300 East Asians).The distribution of ACE genotypes showed significant differences in the entire population (P=0.004) and in East Asians (P=0.005)but not in Caucasians (P=0.23).Allelic frequencies of ACE showed significant differences in East Asians [odds ratio (OR)=1.49 (1.11-2.02)].The meta-analysis with a random effects model showed a significant associa-tion between ACE allele I/D and ACEI-related cough [random effects (RE) OR=1.49 (1.11-2.02),P=0.009] in East Asians,but not in Caucasians [RE OR=0.90 (0.60-1.35)].The allelic frequencies of the bradykinin B 2 receptor gene were significantly different [OR=2.25 (1.42-3.57)].The distributions of the T/C genotypes of the bradykinin B 2 receptor gene were significantly dif-ferent (χ 2=8.366,P=0.015).The meta-analyses re-vealed that there was a significant association between the bradykinin B 2 receptor allele and ACEI-related cough in East Asians [RE OR=2.29 (1.42-3.69),P=0.001].CONCLUSION:ACE I/D and Bradykinin B 2 receptor polymorphisms contributed to the risk of ACEI-related cough in East Asians,but a negative association be-tween ACE I/D polymorphism and ACEI-related cough was observed in Caucasians.

ACEI和ARB对慢性肾脏病患者预后的影响分析

目的 研讨血管紧张素转化酶抑制剂(ACEI)和血管紧张素Ⅱ受体拮抗剂(ARB)对慢性肾脏病(CKD)患者预后的影响。方法 选取88例慢性肾脏病患者,随机分成对照组、观察组,各44例。对照组采用ACEI治疗,观察组采用ARB治疗。比较两组的治疗效果、肾功能相关指标、心功能指标、生活质量评分、不良反应发生情况。结果 两组的治疗总有效率均较高(P>0.05)。观察组治疗后的尿素氮(9.25±1.05)mmol/L、血肌酐(142.56±32.08)μmol/L均低于对照组的(12.56±5.25)mmol/L、(252.26±55.16)μmol/L,血肌酐清除率(96.41±2.08)ml/min高于对照组的(88.56±8.25)ml/min(P<0.05)。观察组治疗后的左室收缩末期内径(LVESD)(46.25±1.06)mm、左室舒张末期内径(LVEDD)(50.26±0.36)mm小于对照组的(49.26±5.26)、(57.15±2.56)mm,左室射血分数(LVEF)(44.89±1.08)%高于对照组的(41.26±5.62)%(P<0.05)。观察组治疗后的活力状况、生理职能、情感职能、社会功能评分分别为(68.44±1.54)、(64.99±2.10)、(68.48±2.15)、(62.48±1.08)分,均高于对照组的(59.48±6.50)、(58.48±8.10)、(59.48±8.41)、(59.71±0.36)分(P<0.05)。两组的不良反应发生率均较低(P>0.05)。结论 ACEI和ARB治疗慢性肾脏病均有一定疗效,但ARB更能显著改善患者的肾功能指标与心功能指标,更有助于提升生活质量。

Optimization of angiotensin I-converting enzyme (ACE) inhibition by rice dregs hydrolysates using response surface methodology

Angiotensin I-converting enzyme (ACE) inhibitory peptides have been shown to have antihypertensive effects and have been utilized for physiologically functional foods and pharmaceuticals. The ACE inhibitory ability of a hydrolysate is de- termined by its peptide composition. However, the peptide composition of a hydrolysate depends on proteolytic enzyme and the hydrolysis conditions. In this study, the effect of process conditions on the ACE inhibitory activity of rice dregs hydrolyzed with a trypsin was investigated systematically using response surface methodology. It was shown that the ACE inhibitory activity of rice dregs hydrolysates could be controlled by regulation of five process conditions. Hydrolysis conditions for optimal ACE inhibition were defined using the response surface model of fractional factorial design (FFD), steepest ascent design, and central composite design (CCD).

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。

A Meta-analysis of angitensin-converting enzyme inhibitors on normotensive early diabetic renal diseases

Objective: To make a systematic assessment on whether the progression of early diabetic renal disease with normotension may be slowed down by angiotensin-converting enzyme (ACE) inhibitors. Methods: Randomized clinical experiments published on MEDLINE from January 1990 to April 1999 and on China Biological Medicine were reviewed for studying the effects of ACE-inhibitors on normotensive patients with early diabetic renal diseases. Based on the inclusion criteria, 10 studies were selected. Their results were combined and analyzed with RevMan3. I software. Results: The pooled effect of urinary microalbumin excretion rate, systolic blood pressure, diastolic blood pressure and mean arterial blood pressure were -77.502 mg/24 h (-100.748 to-54.256), -5.002 mmHg [-9.630 to 0.685],-2.949 mmHg (-4.005 to 1.892). -4.284 mmHg (-5.444 to 3.123) respectively. Using clinical albuminuria as the end-point, the pooled odd ratio was 0.27 [95% CI 0.18 0.40]. The sub-group analysis showed that those results had no difference between type 1 and type 2 diabetes. There was no significant correlation between the pooled effects of urinary micro-albuminuria excretion rate and systolic blood pressure. diastolic blood pressure or mean arterial blood pressure. Conclusion: ACE inhibitors can decline urinary micro-albuminuria excretion rate in normotensive patients with early diabetic renal disease and delay the progression of early diabetic renal disease to clinical albuminuria. These effects may not be dependent on its blood pressure-reduction effect.

ACEI/ARB对新型冠状病毒肺炎合并高血压病人预后的影响

目的:分析血管紧张素Ⅱ受体拮抗剂(ARB)/血管紧张素转换酶抑制剂(ACEI)类药物对新型冠状病毒肺炎(COVID-19)合并高血压病人各项临床指标及预后的影响,并探讨其临床应用价值。方法:选取2020年1月14日—2020年2月18日山西省各地区医院确诊COVID-19病人76例,根据是否合并高血压分为高血压组(21例)和非高血压组(55例);根据高血压病人是否长期服用ACEI/ARB类药物分为使用ACEI/ARB组(11例)和使用其他药物组(10例)。记录并比较病人相关病史及入院后一般生命体征、血常规、降钙素原(PCT)、C反应蛋白(CRP)、肝功能、肾功能、心肌损伤标志物等。比较病人出院后1个月、6个月、12个月的随访指标。结果:与非高血压组比较,高血压组病人年龄较大,体质指数(BMI)值较高,收缩压(SBP)、舒张压(DBP)增高,白细胞及中性粒细胞增多(P<0.05);使用其他药物组与使用ACEI/ARB组病人一般资料比较,差异均无统计学意义(P>0.05);使用ACEI/ARB组和使用其他药物组各指标随访结果比较,差异均无统计学意义(P>0.05)。结论:ACEI/ARB类药物并未对COVID-19合并高血压病人各项临床指标产生明显影响,且不影响该类病人的预后,可以考虑继续服用ACEI/ARB进行临床治疗。

黄葵胶囊联合ACEI/ARB类药物治疗早期糖尿病肾病随机对照研究的Meta分析和试验序贯分析

目的:基于Meta分析和试验序贯分析(TSA),评价黄葵胶囊联合血管紧张素转换酶抑制剂(ACEI)/血管紧张素Ⅱ受体拮抗剂(ARB)类药物治疗早期糖尿病肾病的临床疗效及安全性。方法:检索主要的中英文数据库,收集建库至2021年4月18日有关黄葵胶囊治疗早期糖尿病肾病的随机对照试验(RCT)。由2名研究员进行文献筛选和信息提取,并评价所纳入研究的质量及偏倚风险,采用RevMan 5.3软件进行结局指标的分析,采用TSA 0.9.5.10 Beta软件进行TSA。结果:最终纳入25项RCT,共1 895例患者(研究组949例,对照组946例)。Meta分析结果显示,黄葵胶囊联合ACEI/ARB类药物的治疗方案优于单用ACEI/ARB类药物的治疗方案,其中临床总有效率(RR=1.26,95%CI=1.17~1.34,P<0.000 01)、尿白蛋白排泄率(MD=-17.95,95%CI=-22.45~-13.44,P<0.000 01)、血肌酐水平(MD=-7.24,95%CI=-12.26~-2.23,P=0.005)、血尿素氮水平(MD=-0.33,95%CI=-0.51~-0.14,P=0.000 4)、三酰甘油水平(MD=-0.30,95%CI=-0.38~-0.21,P<0.000 01)和总胆固醇水平(MD=-0.52,95%CI=-0.78~-0.27,P<0.000 1)的差异均有统计学意义;经亚组分析,病程、年龄和疗程可能与尿白蛋白排泄率有关;所有纳入的研究均未报告出现严重不良反应,两组患者不良反应发生率的差异无统计学意义(P>0.05);对尿白蛋白排泄率进行TSA,显示样本量充足,研究组患者的疗效优于对照组,证据确切。结论:黄葵胶囊联合ACEI/ARB类药物治疗早期糖尿病肾病可提高临床总有效率,降低蛋白尿,改善肾功能,调整血脂水平,安全性好,具有一定的临床应用前景。由于纳入的文献质量一般及研究方法学质量不高,仍需更多高质量、多中心、大样本的RCT进行确证。

Prevention of atrial fibrillation with renin-angiotensin system inhibitors on essential hypertensive patients:a meta-analysis of randomized controlled trials

We aimed to investigate the effectiveness and safety of angiotensin-converting enzyme inhibitors （ACEIs） or angiotensin Ⅱ receptor blockers （ARBs） on preventing atrial fibrillation in essential hypertensive patients. Systematic literature retrieval was carried out to obtain randomized controlled trials on the effects of ACEI/ ARBs on essential hypertensive patients before December, 2013. Data extraction and quality evaluation were performed. Meta-analysis was performed by Review Manager 5.2.3. Ten high quality studies （11 articles） with a total of 42,892 patients （20,491 patients in the ACEI/ARBs group and 22,401 patients in the β-blocker or the calcium antagonist group） met the inclusion criteria and were included in the meta-analysis. The results showed that ACEI/ARBs reduced the incidence of atrial fibrillation （AF） recurrence compared to calcium antagonists （RR=0.48; 95%CI, 0.40-0.58; P〈0.00001） or β-blockers （RR=0.39; 95%CI, 0.20-0.74; P=0.005） in long-term follow-up, respectively. Furthermore, ACEI/ARBs reduced the incidence of conges- tive heart failure （RR=0.86; 95%CI, 0.77-0.96; P=0.007）. However, no significant effects were observed on the incidence of new AF, cardiac death, myocardial infarction, and stroke. Our results suggest that ACEI/ ARBs may reduce the incidence of AF recurrence and congestive heart failure, with fewer serious adverse effects.

Time to re-evaluate effects of renin-angiotensin system inhibitors on renal and cardiovascular outcomes in diabetic nephropathy

The use of renin-angiotensin system(RAS) inhibitors, such angiotensin converting enzyme inhibitors/angiotensin-Ⅱreceptor blockers, to slow progression of chronic kidney disease(CKD) in a large group dominated by elderly people in the real world is not supported by available evidence. Large-scale clinical trials had many faults,among them a lack of focus on the elderly. However,it would be difficult to conduct clinical trials of a similar scale in elderly CKD patients. Besides, progression ofkidney disease is often slow in elderly persons, and the vast majority of older adults with CKD will die before reaching end stage renal disease. Moreover, since it is not clear that progression of kidney disease, and even of proteinuric diabetic nephropathy, is not inhibited through the use of RAS inhibitors, the most patientcentric goal of therapy for many elderly individuals should be individualized.

ACEI联合恩格列净治疗早中期糖尿病肾病的疗效观察

目的探讨血管紧张素转换酶抑制剂(ACEI)联合恩格列净治疗早中期糖尿病肾病的疗效。方法86例早中期糖尿病肾病患者,以奇偶法分为实验组与常规组,各43例。常规组采用常规疗法,实验组采用ACEI联合恩格列净治疗。比较两组疗效、治疗前后尿肾病相关指标[尿微量白蛋白(mALB)、尿白蛋白与肌酐比(UACR)、尿N-乙酰-β-D-葡萄糖苷酶(NAG)]、血糖指标(空腹血糖、餐后2 h血糖、糖化血红蛋白)。结果实验组治疗总有效率95.3%高于常规组的79.1%,差异有统计学意义(P<0.05)。治疗后,两组NAG、UACR、mALB均较治疗前下降,且实验组NAG(14.04±4.51)U/L、UACR(30.34±5.21)mg/g、mALB(29.90±6.86)mg/L低于常规组的(16.69±5.47)U/L、(54.35±10.28)mg/g、(35.33±8.28)mg/L,差异有统计学意义(P<0.05)。治疗后,两组空腹血糖、餐后2 h血糖、糖化血红蛋白均较治疗前降低,且实验组空腹血糖(5.42±0.28)mmol/L、餐后2 h血糖(6.42±0.21)mmol/L、糖化血红蛋白(6.31±1.31)%低于常规组的(6.02±0.41)mmol/L、(9.13±1.52)mmol/L、(7.82±1.03)%,差异有统计学意义(P<0.05)。结论ACEI联合恩格列净治疗早中期糖尿病肾病,可有效改善患者临床症状与尿肾病指标,还能控制患者血糖值处于稳定状态,适合临床深入研究与推广应用。