Comparison of Angiotensin Receptor Blockers and Angiotensin-Converting Enzyme Inhibitors in the Management of Arterial Stiffness and Target Organ Damage in Patients with Hypertension

Abstract Background Arterial stiffness and hypertension are strong predictors of cardiovascular disease and mortality. Angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) are first-line antihypertensive agents in reducing blood pressure and arterial stiffness. Objective The objective of this study was to compare the effects of ACEI and ARB in reducing arterial stiffness and preventing target organ damage in patients with hypertension. Methods This observational study included 654 participants who attend routine consultations at an outpatient hypertension clinic in 2 university hospitals. Patients were interviewed, and they underwent central and peripheral blood pressure measurements. Doppler echocardiography, carotid ultrasound, biochemical tests, and anthropometric parameters were carried out. Shapiro-Wilk, chi-square, and Fisher's exact test were used. A significance level of 5% was adopted. Results A total of 659 participants were evaluated in the study (398 from the ARB group and 256 from the ACEI group). Age, body mass index (BMI), central and peripheral blood pressure measurements, pulse wave velocity (PWV), left ventricular mass index, and carotid intima-media thickness did not show differences between the groups (p > 0.05). After linear regression analysis, the ACEI group had lower values of total vascular resistance (TVR) (p = 0.003) and augmentation pressure (p = 0.008), when compared to the ARB group. Conclusion This study showed that the ACEI group had a greater reduction in augmentation pressure and PWV. There were no differences between the groups regarding the improvement of outcomes related to central arterial pressure, PWV, and cardiac and vascular target organ damage.

Bloqueo del eje renina angiontensina aldosterona (RAAS) en la enfermedad renal diabética. Más allá del control de la hipertensión arterial / Renin angiotensin aldosterone system (RAAS) and its suppression in diabetic kidney disease. Control of arterial hypertension and beyond

La enfermedad renal diabética (ERD) es una comorbilidad con alta prevalencia a nivel mundial, siendo una de las complicaciones más frecuentes de la diabetes mellitus (DM). La ERD se relaciona con complicaciones cardiovasculares y progresión de la enfermedad renal crónica (ERC), por ello la identificación de factores modificables, como el control de la presión arterial, es uno de los pilares más importantes en el manejo integral. En esta revisión hacemos un recorrido sobre el papel de la hipertensión y el bloqueo del eje renina angiotensina aldosterona (RAAS) en el curso de la ERD y las estrategias terapéuticas orientadas a la reducción de la presión arterial (PA), el bloqueo RAAS y el impacto en resultados renales y cardiovasculares. El objetivo de este artículo es hacer una revisión de las intervenciones más importantes que actúan bloqueando el eje renina angiotensina aldosterona (RAAS) y determinar si estas medidas en los pacientes con ERD, solo tienen impacto en el control de la presión arterial o si también son estrategias de nefro y cardio-protección. Conclusión: La ERD es una de las complicaciones más frecuentes de la diabetes mellitus (DM). El control de la PA sigue siendo un pilar fundamental para lograr estos objetivos. Los bloqueadores del RAAS (iECAS y BRAs) son los antihipertensivos de elección con efecto terapéutico por el bloqueo RAAS y esto les permite tener además del control de la PA, efectos nefroprotectores y cardioprotectores importantes en pacientes con ERD, sobre todo cuando hay la presencia de albuminuria. Evaluamos que además de los inhibidores de la enzima convertidora de angiotensina (iECAs) y los bloqueadores del receptor de angiotensina (BRAs), vienen tomando importancia los antagonistas selectivos del receptor mineralocorticoide (ARM) como Finerenona.

Diabetic kidney disease (DKD) is a comorbidity with a high worldwide prevalence, and one of the most frequent complications of diabetes mellitus (DM). CKD is related to cardiovascular complications and the progression of chronic kidney disease (CKD), therefore the identification of modifiable factors, such as blood pressure control, is one of the most important pillars in comprehensive management. In this review, we will analyze the role of hypertension and the renin-angiotensin-aldosterone system (RAAS) and its suppression in the course of CKD, and therapeutic strategies aimed at reducing blood pressure (BP), RAAS blockade, and the impact on renal and cardiovascular outcomes. The objective of this article is to review the most important interventions that act by blocking the renin-angiotensin-aldosterone system (RAAS) and to determine if these measures in patients with CKD only have an impact on blood pressure control or if they are also nephron and cardio-protective strategies. Conclusion: DKD is one of the most frequent complications of diabetes mellitus (DM). BP control continues to be a fundamental pillar to achieve these objectives. RAAS blockers (iECAS and ARBs) are the first-line antihypertensive with a therapeutic effect due to RAAS blockade and this allows them to have, in addition to BP control, important nephroprotective and cardioprotective effects in patients with CKD, especially when there is albuminuria. We evaluated that in addition to angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), selective mineralocorticoid receptor antagonists (MRA) such as Finerenone are gaining importance.

The use of angiotensin receptor blockers in dementia prevention / O uso de bloqueadores de receptor de angiotensina na prevenção de demência

ABSTRACT: Alzheimer's disease (AD) and dementia are preventable and highly prevalent diseases, as is systemic arterial hypertension. Thus, it is speculated that angiotensin receptor blockers (ARBs) may be neuroprotective against AD. Objective: The aim of this study was to evaluate if the use of ARBs confers a neuroprotective effect on AD, through a systematic review. Methods: Studies published on Embase, LILACS, SciELO, and PubMed were evaluated. The selection of the studies included those that evaluated the use of antihypertensive drugs in individuals with a previous diagnosis of mild cognitive impairment. The data were extracted with the Cochrane Effective Practice and Organization of Care (EPOC) form. The risk of bias was evaluated by the EPOC "Risk of bias tool." Results: A total of 12 articles were identified, and 3 articles were selected. Two of them analyzed the use of ARB/ACEI versus other antihypertensives and the development of dementia. Conclusion: There is a tendency for ARBs to be superior to other antihypertensives in preventing dementia.

RESUMO: A doença de Alzheimer (DA) e a demência são doenças potencialmente preveníveis, assim como a hipertensão arterial sistêmica. Dessa forma, especula-se que os bloqueadores dos receptores de angiotensina (BRA) tenham efeito neuroprotetor contra a DA. Objetivo: Avaliar se o uso de BRA confere efeito neuroprotetor para DA, por meio de uma revisão sistemática. Métodos: Foram avaliados estudos publicados nas plataformas Embase, Literatura Latino-Americana e do Caribe em Ciências da Saúde (Lilacs), Scientific Electronic Library Online (SciELO) e United States National Library of Medicine (PubMed). Os estudos incluídos avaliaram o uso de anti-hipertensivos em indivíduos com diagnóstico prévio de comprometimento cognitivo leve. Os dados foram extraídos com base no formulário da EPOC. Risco de viés foi avaliado por meio da ferramenta da Cochrane Effective Practice and Organisation of Care (EPOC) "Risk of bias tool". Resultados: Foram encontrados 12 artigos e três foram selecionados. Dois analisaram o uso de BRA/IECA vs. o uso de outros anti-hipertensivos e o desenvolvimento de demência. Conclusão: Há uma tendência de que os BRA sejam superiores a outros anti-hipertensivos na prevenção da demência.

Associação entre o Antagonismo do Sistema Renina-Angiotensina-Aldosterona e a Mortalidade Relacionada à COVID-19 em Pacientes com Hipertensão Relacionada ao Sobrepeso/Obesidade: um Estudo Retrospectivo de Coorte / Association between RAAS Antagonism and COVID-19-related Mortality in Patients with Overweight/Obesity-related Hypertension: A Retrospective Cohort Study

Resumo Fundamento Os bloqueadores dos receptores da angiotensina (BRA) e os inibidores da enzima conversora da angiotensina (IECA) aumentam a expressão de ACE2, que é um receptor para entrada de SARS-CoV-2 nas células. Embora as evidências sugiram que os IECA/BRA são seguros entre a população geral com COVID-19, sua segurança em pacientes com hipertensão relacionada ao sobrepeso/obesidade merece uma avaliação mais aprofundada. Objetivo Avaliamos a associação entre o uso de IECA/BRA e a gravidade da COVID-19 em pacientes com hipertensão relacionada ao sobrepeso/obesidade. Métodos O presente estudo incluiu 439 pacientes adultos com sobrepeso/obesidade (índice de massa corporal ≥ 25 kg/m2) e hipertensão, diagnosticados com COVID-19 e internados no University of Iowa Hospitals and Clinic entre 1º de março e 7 de dezembro de 2020. Foram avaliadas a mortalidade e a gravidade da COVID-19 com base no tempo de internação hospitalar, internação em unidade de terapia intensiva, uso de oxigênio suplementar, ventilação mecânica e uso de vasopressores. A regressão logística multivariável foi usada para examinar as associações do uso de IECA/BRA com a mortalidade e outros marcadores de gravidade de COVID-19, com um alfa bilateral definido em 0,05. Resultados A exposição aos BRA (n = 91) e IECA (n = 149) antes da hospitalização foi significativamente associada a menor mortalidade ( odds ratio [OR] = 0,362, intervalo de confiança [IC] de 95% 0,149 a 0,880, p = 0,025) e menor tempo de internação hospitalar (IC 95% −0,217 a −0,025, p = 0,015). Adicionalmente, os pacientes em uso de IECA/BRA apresentaram uma tendência não significativa de menor internação em unidade de terapia intensiva (OR = 0,727, IC 95% 0,485 a 1,090, p = 0,123), uso de oxigênio suplementar (OR = 0,929, IC 95% 0,608 a 1,421,p = 0,734), ventilação mecânica (OR = 0,728, IC 95% 0,457 a 1,161, p = 0,182) e vasopressores (OR = 0,677, IC 95% 0,430 a 1,067, p = 0,093). Conclusão Os resultados sugerem que pacientes internados com COVID-19 e hipertensão relacionada ao sobrepeso/obesidade que receberam IECA/BRA antes da internação apresentam menor mortalidade e COVID-19 menos grave do que aqueles que não estavam tomando IECA/BRA. Os resultados também sugerem que a exposição aos IECA/BRA pode proteger pacientes com hipertensão relacionada ao sobrepeso/obesidade de COVID-19 grave e morte.

Abstract Background Angiotensin receptor blockers (ARB) and angiotensin-converting enzyme inhibitors (ACEI) increase the expression of ACE2, which is a receptor for entry of SARS-CoV-2 into cells. Though evidence suggests that ARB/ACEI are safe among the general population with COVID-19, their safety in patients with overweight/obesity-related hypertension deserves further evaluation. Objective We assessed the association between ARB/ACEI use and COVID-19 severity in patients with overweight/obesity-related hypertension. Methods This study included 439 adult patients with overweight/obesity (body mass index ≥ 25 kg/m2) and hypertension, diagnosed with COVID-19 and admitted to University of Iowa Hospitals and Clinic from March 1 to December 7, 2020. Mortality and severity of COVID-19 were evaluated based on length of stay in hospital, intensive care unit admission, use of supplemental oxygen, mechanical ventilation, and vasopressors. Multivariable logistic regression was used to examine the associations of ARB/ACEI use with mortality and other markers of COVID-19 severity, with a two-sided alpha set at 0.05. Results Exposure to ARB (n = 91) and ACEI (n = 149) before hospitalization was significantly associated with lower mortality (odds ratio [OR] = 0.362, 95% confidence interval [CI] 0.149 to 0.880, p = 0.025) and a shorter length of stay (95% CI −0.217 to −0.025, p = 0.015). Additionally, patients using ARB/ACEI showed a non-significant trend toward lower intensive care unit admission (OR = 0.727, 95% CI 0.485 to 1.090, p = 0.123), use of supplemental oxygen (OR = 0.929, 95% CI 0.608 to 1.421, p = 0.734), mechanical ventilation (OR = 0.728, 95% CI 0.457 to 1.161, p = 0.182), and vasopressors (OR = 0.677, 95% CI 0.430 to 1.067, p = 0.093). Conclusion Results suggest that hospitalized patients with COVID-19 and overweight/obesity-related hypertension who were prescribed ARB/ACEI before admission to the hospital exhibit lower mortality and less severe COVID-19 than those who were not taking ARB/ACEI. The results also suggest that exposure to ARB/ACEI may protect patients with overweight/obesity-related hypertension from severe COVID-19 and death.

Angiotensin receptor-neprilysin inhibitors and cardiac remodeling

The aim of this study was to determine how sacubitril/valsartan compared with valsartan in an outpatient setting affects left ventricular remodeling in heart failure with reduced ejection fraction and functional (or secondary) mitral regurgitation (SMR) due to the effect of dual inhibition of the renin-angiotensin system and neprilysin. The outpatient study included 90 patients with chronic SMR who were followed up for 12 months. They received sacubitril/valsartan or valsartan instead of the more commonly used angiotensin-converting enzyme inhibitor enalapril for heart failure, in addition to standard medical therapy for heart failure. The difference in NT-proBNP change between groups was the primary endpoint. Changes in effective regurgitation orifice area, left ventricular ejection fraction, left ventricular end-systolic and end-diastolic volume indices, left atrial volume index, E/e' index, and exercise tolerance on the 6-minute walk test were secondary endpoints. In the treatment efficacy analysis, NT-proBNP levels decreased significantly by 37% in the sacubitril/valsartan group and by 11% in the valsartan group (P<0.001). Ejection fraction and exercise tolerance (increase in walking distance in the 6-min test) increased in the sacubitril/valsartan group (P<0.05). Also, in this group, the effective area of the regurgitation orifice, the left atrial volume index, the E/e' index, and the indices of the end-systolic and end-diastolic volume of the left ventricle (P<0.05) decreased more pronouncedly. Compared with valsartan, treatment with sacubitril/valsartan led to a significant improvement in cardiac remodeling in patients with SMR and heart failure with reduced ejection fraction.

Use of Diuretics is Associated with Higher Risk of Sarcopenia in Older Adults with Hypertension

Abstract Background: Sarcopenia is a disease that involves skeletal muscle mass loss and is highly prevalent in the older adult population. Moreover, the incidence of sarcopenia is increased in patients with hypertension. Objectives: The study aimed to evaluate the association between the classes of the drugs used for arterial hypertension treatment and the presence or absence of sarcopenia. Methods: 129 older adults with hypertension were evaluated by the researchers who registered the participants medication for arterial hypertension treatment. Sarcopenia level was measured by anthropometric parameters, muscular strength, and functional capacity. The data were analyzed by one-way ANOVA followed by post-hoc test and Fisher's exact test; statistical significance was set at 0.05. Results: Age was not different between women with different levels of sarcopenia, but significant differences were observed between men with absent sarcopenia (66.8±4.2 years) and men with probable sarcopenia (77.0±10.2 years). Individuals with absent sarcopenia showed higher handgrip strength (men: 33.8±7.4, women: 23.2±4.6 Kgf) in comparison with those with sarcopenia (men with probable sarcopenia: 9.5±3.3 Kgf, women with probable, confirmed, and severe sarcopenia: 11.7±2.5, 12.2±3.0, 11.8±1.8 Kgf, respectively). The analysis showed an association between the type of medication and degree of sarcopenia; diuretics were significantly associated with probable sarcopenia, and angiotensin II receptor blockers (alone or in combination with diuretics) was associated with absence of sarcopenia. Conclusion: In conclusion, handgrip strength was a good method to diagnose sarcopenia, and diuretics were associated with increased risk of sarcopenia in older adults with hypertension.

Uso previo de antagonistas de la angiotensina II en pacientes hipertensos hospitalizados y mortalidad por COVID-19

Introducción: Actualmente existe un gran interés en establecer la relación entre la severidad de la infección por SARS-COV-2 en pacientes hipertensos usuarios de antagonistas de la angiotensina II (ARAII). Objetivo: Estudiar la relación entre el uso previo de antagonistas de la ARA II en pacientes hipertensos y la mortalidad por COVID-19. Materiales y métodos: Se realizó un estudio observacional retrospectivo en un hospital de referencia en Lima, Perú, en pacientes hipertensos hospitalizados en marzo del 2021 por COVID-19 severo. Resultados: Ingresaron al estudio 101 pacientes, con una media de edad de 70.1 + 12.0 y sexo masculino 48%. Los usuarios de ARAII fueron 45 (45.6%) y no los tomaban 56 (54.4%). El Índice de comorbilidad de Charlson fue mayor en el grupo ARAII (3.6 + 1.56 vs 3.04 + 1.24) (p<0.05). La mortalidad total y por sexo (varones vs mujeres), entre los que usaban ARAII o no, fueron 57.8% vs 62% (p = 0.633) y 36.36% vs 63.64 % (p<0.05), respectivamente. La media de la concentración de deshidrogenasa láctica fue menor en los que tomaban ARAII comparado con los no usuarios, 394.18 + 152.3 vs 503.5 + 252.7 (p<0.05); no se observó diferencia significativa en el recuento de leucocitos, niveles séricos de Proteína C Reactiva, Ferritina, dímero D y fibrinógeno. Conclusión: Entre los pacientes hospitalizados con COVID-19 con hipertensión, el uso previo de ARAII no se asoció con riesgo de mortalidad.

Background: There is caurrently great interest in establishing the relationship between the severity of SARS-COV-2 infection in hypertensive patients who use angiotensin II antagonists (AIIRAs). Objective: To study the relationship between the previous use of angiotensin II antagonists (ARB) in hypertensive patients and mortality from COVID-19. Materials and methods: A retrospective observational study was carried out in a tertiary care hospital in Lima, Peru, in hypertensive patients hospitalized in March 2021 for severe COVID-19. Results: A total of 101 patients entered the study, with a mean age of 70.1 + 12.0 and 48% male. ARB users and non-users were 45 (45.6%) and 56 (54.4%), respectively. The Charlson Comorbidity Index was higher in the ARB group (3.6 + 1.56 vs 3.04 + 1.24) (p<0.05). Total and male vs women mortality, among those using ARBs or not, were 57.8% vs 62% (p = 0.633) and 36.36% vs 63.64% (p <0.05), respectively. Mean lactate dehydrogenase concentration was lower in those taking ARBs compared to non-users, 394.18 + 152.3 vs 503.5 + 252.7 (p<0.05); No significant difference was observed in the leukocyte count and serum levels of C-Reactive Protein, Ferritin, D-dimer and fibrinogen. Conclusion: Among hospitalized COVID-19 patients with hypertension, prior use of ARBSs was not associated with mortality risk.

AMPA and angiotensin type 1 receptors are necessary for hemorrhage-induced vasopressin secretion

Hypovolemia induced by hemorrhage is a common clinical complication, which stimulates vasopressin (AVP) secretion by the neurohypophysis in order to retain body water and maintain blood pressure. To evaluate the role of brain L-glutamate and angiotensin II on AVP secretion induced by hypovolemia we induced hemorrhage (∼25% of blood volume) after intracerebroventricular (icv) administration of AP5, NBQX, or losartan, which are NMDA, AMPA, and AT1 receptor antagonists, respectively. Hemorrhage significantly increased plasma AVP levels in all groups. The icv injection of AP5 did not change AVP secretion in response to hemorrhage. Conversely, icv administration of both NBQX and losartan significantly decreased plasma AVP levels after hemorrhage. Therefore, the blockade of AMPA and AT1 receptors impaired AVP secretion in response to hemorrhage, suggesting that L-glutamate and angiotensin II acted in these receptors to increase AVP secretion in response to hemorrhage-induced hypovolemia.

Effects of antihypertensive drugs on renal function after percutaneous transluminal coronary angioplasty / 药学实践杂志

Objective To evaluate the effects of antihypertensive drugs on renal function after percutaneous transluminal coronary angioplasty. Methods A retrospective analysis was performed on 193 patients who underwent percutaneous transluminal coronary angioplasty and took antihypertensive drugs regularly. Those patients were admitted to Nanjing Drum Tower Hospital during January 2020 to December 2020. The patients were divided into ACEI/ARB group, β-blockers, calcium channel blockers and hydration control group. All patients received routine hydration during the perioperative period. The changes of serum creatinine (Scr), blood urea nitrogen (BUN), estimated glomerular filtration rate(eGFR) and endogenous creatinine clearance rate (Ccr) before and after operation were compared. Results The incidence of CIN was 0% in four groups. Compared with the preoperative, there was no significant change in Scr and Ccr in every group. Except for the hydration control group, the BUN levels in three treated groups were reduced after postoperative. Specifically, the BUN reduction in β-blockers group has statistically significant difference compared to the hydration control group and CCB group. In addition, eGFR levels were significantly reduced in the β-blockers group. Preoperative Scr and Ccr levels in patients with high blood pressure (SBP≥140 or DBP≥90) were significantly different from the patients with normal blood pressure (SBP<140 and DBP<90). Conclusion The use of ACEI/ARB and CCB before percutaneous transluminal coronary angioplasty had no effect on renal function in the short term. β-blockers can slightly reduce renal function, especially in patients with high blood pressure, who should receive special attention.

Angiotensin receptor neprilysin inhibitor in elderly with hypertension / 中国临床药理学与治疗学

Angiotensin receptor/neprilysin inhibitor (ARNI) is a novel combination drug that is a dual inhibitor of angiotensin receptor and neprilysin. In June 2021, the National Medical Products Administration approved ARNI for hypertension indications. This review provides an update of current literature on ARNI in elderly hypertension.

Progress of pharmacotherapy for heart failure / 中国临床药理学与治疗学

Heart failure is the terminal stage of all kinds of heart diseases. Despite the use of a variety of traditional drug standard treatment, the prognosis is still not ideal, and there is an urgent need for the update and improvement of new drugs and treatment methods. In recent years, angiotensin receptor-enkephalase inhibitors (Sacubitril/Valsartan), sodium-glucose cotransporter 2 inhibitors (SGLT-2i), soluble guanoside cyclase agonists (Vericiguat) and myocardial myosin activators omecamtiv mecarbil have been developed successively. SGLT2 inhibitors can improve ventricular load, reduce fibrosis and affect myocardial metabolism. sGC agonists play an anti-heart failure role by enhancing l-ARg-No-SGC-CGMP signaling pathway, improving myocardial and vascular function, reversing ventricular hypertrophy and fibrosis, slowing ventricular remodeling, and reducing ventricular afterload through systemic and pulmonary vasodilation. In addition, fineridone, a novel salt corticosteroid receptor antagonist, has also been reported in clinical studies in the field of heart failure. Therefore, it is the direction and hope for the development of heart failure in the future to select appropriate drugs for different types of patients with heart failure and carry out individualized treatment according to the optimized process of heart failure.

Protective Effect of Quercetin on Renal Tubular Cells and the Involvement with the Renin-Angiotensin-Aldosterone Axis

Abstract Ischemia-reperfusion (I/R) plays an important role in the process of acute kidney injury (AKI) due to the generation of reactive oxygen species (ROS). Substances of natural origin have been studied in the prevention of oxidative damage related to I/R. Quercetin is a flavonoid with antioxidant potential and modulate enzymes, such the inhibition of the Rennin-Angiotensin System (RAS). The aim of this study is to evaluate the nephroprotective effect of quercetin against the I/R and analyze the inhibition of RAS. Rhesus monkey Kidney Epithelial Cells (LLC-MK2 line) were submitted to an in vitro ischemia/reperfusion model. After the reperfusion cells were treated with quercetin, the cell viability was accessed by the MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) assay. Tubular cell damage was assessed by the Kidney Injury Molecule-1 (KIM-1) measurement. Oxidative stress was evaluated through Thiobarbituric Acid Reactive Substances (TBARS) and reduced glutathione (GSH). The evaluation of cell death and the mitochondrial depolarization were analyzed by flow cytometry. Quercetin prevents cell death reducing oxidative stress and preventing mitochondrial membrane depolarization. Molecular docking showed that quercetin prevents cell damage better than losartan and lisinopril, inhibitors of RAS. Quercetin has a potential to interact with type 1 angiotensin II receptor (AT1) with greater affinity through the formation of five hydrogen bonds of strong intensity.

Review of novel compounds that act on the AT2 receptor / 药学学报

Selective activation or inhibition of the angiotensin II type 2 (AT2) receptor can cause vasodilation, decrease cell proliferation, promote neurite outgrowth and block neuronal excitability. The AT2 receptor can be used as a potential drug target for the treatment of cardiovascular diseases, fibrosis, inflammation, neuronal diseases and tumors. Research and development of new drugs that selectively act on the AT2 receptor and the mechanism of intracellular signal transduction involving the AT2 receptor is a challenging but worthy endeavor. We review research progress on the AT2 receptor and compounds that act on the AT2 receptor, along with structure-activity relationship analysis, to provide reference and guidance for further research in this field.

Analyzing the clinical phenotype of heart disease caused by the double mutation of p.Gly743Arg and p.Glu1389Lys carrying the myosin heavy chain gene / 中华危重病急救医学

Objective:To investigate the relationship between double mutations of myosin heavy chain gene (MYH6) p.Gly743Arg and p.Glu1389Lys and the cardiac phenotype.Methods:Patients carrying double mutations in the MYH6 gene p.Gly743Arg and p.Glu1389Lys were screened from 52 unrelated left ventricular hypertrophy (LVH) who were admitted to the Second Hospital of Chongqing Medical University from 2015 to 2020, and the genetic testing of peripheral blood of patients by second-generation whole-exome sequencing assay technology and genomic DNA of their family members Sanger sequencing was performed to validate the genomic DNA of the family members. The cardiac phenotype was evaluated by electrocardiogram, coronary computed tomography angiography (CTA), echocardiography, and cardiac magnetic resonance imaging (MRI) as adjuncts.Results:All whole-exome gene were detected in 52 unrelated patients with LVH, of which 1 patient (1.9%) had double mutations in MYH6 gene p.Gly743Arg and p.Glu1389Lys (proband). Two members of the maternal line of this patient carried p.Glu1389Lys mutation, but there was no obvious clinical phenotype. Two members of the paternal line carried p.Gly743Arg mutation and had obvious clinical phenotype of bradycardia, but there was no LVH. The male proband, aged 21 years old, presented with LVH and sinus bradycardia but no coronary artery stenosis on CTA before treatment, MRI showed that the left ventricular end diastolic diameter was 58 mm. After treatment with angiotensin receptor-enkephalinase inhibitor (ARNI), electrocardiogram showed that the heart rate increased significantly (from 43 bpm to 72 bpm). Echocardiography showed that the left ventricular end diastolic diameter decreased significantly (from 60 mm to 49 mm).Conclusions:The p.Glu1389Lys mutation of the MYH6 gene may not manifest the phenotype of heart disease. MYH6 gene p.Gly743Arg mutation may be manifested asymptomatic sinus bradycardia, but there is no LVH phenotype. The cardiac disease phenotype caused by the double mutations of p.Gly743Arg and p.Glu1389Lys in the MYH6 gene is more obvious. Asymptomatic LVH and sinus bradycardia can appear in adolescence, but the LVH phenotype can be reversed in a short period of time after ARNI treatment.

Impact of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers on in-hospital mortality among patients with COVID-19: a systematic review and meta-analysis

INTRODUCTION@#There are concerns that angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) may worsen the outcomes of patients with COVID-19. This systematic review and meta-analysis aimed to study the in-hospital mortality among COVID-19 patients who were on ACEIs/ARBs as compared to those not on ACEIs/ARBs.@*METHODS@#We searched PubMed, EMBASE, clinicaltrials.gov and Google Scholar between 1 January 2020 and 30 May 2020 to identify all studies that evaluated the use of ACEIs/ARBs and reported the in-hospital mortality outcomes of COVID-19 patients. Nine non-randomised studies were eligible for inclusion in the analysis. The primary outcome studied was the in-hospital mortality of COVID-19 patients who were on ACEIs/ARBs compared with those not on ACEIs/ARBs.@*RESULTS@#Of the 8,313 patients in the nine studies, 7,622 (91.7%) were from studies with all-comers, while 691 (8.3%) were from studies involving only patients with hypertension. 577 (14.6%) in-hospital deaths were observed out of a total of 3,949 patients with an outcome in the nine studies. Overall, no significant difference was observed in the in-hospital mortality between patients on ACEIs/ARBs and those not on ACEIs/ARBs (odds ratio [OR] 1.06, 95% confidence interval [CI] 0.75-1.50; p = 0.73). Further sensitivity analysis in the hypertension group and the all-comers group showed similar results (OR 0.88, 95% CI 0.58-1.32; p = 0.53 and OR 1.85, 95% CI 1.00-3.43; p = 0.05, respectively).@*CONCLUSION@#We observed that ACEIs/ARBs had no significant impact on the in-hospital mortality of COVID-19 patients and can be used safely in patients with indications.

Effects of Sacubitril Valsartan Sodium on Short-term Prognosis of Patients with Acute Anterior Myocardial Infarction Complicated with Acute Cardiac Insufficiency / 中国药房

OBJECTIVE：To investigate the effec ts of angiotensin receptor neprilysin inhibitor （ARNI）sacubitril valsartan sodium（SVS）on the short-term prognosis of patients with acute anterior myocardial infarction （AAMI）complicated with acute cardiac insufficiency. METHODS ：A total of 80 patients with AAMI and Killip grade Ⅱ-Ⅳ of cardiac function ，who met the inclusion criteria ，were randomly divided into ARNI group and control group ，with 40 patients in each group. Both groups were given the same basic standardized drug treatment ，vital signs support treatment and percutaneous coronary intervention treatment at the same time. On this basis ，ARNI group was given SVS tablet orally ，with initial dose of 25 mg each time ，twice a day ； thereafter，gradually adjust the dose to 200 mg each time ，twice a day. Control group was given Enalapril maleate tablets orally ， with an initial dose of 5 mg each time ，twice a day ；thereafter，gradually adjust the dose to 10 mg each time ，twice a day. Both groups took medicine for a long time ，and were followed up after 1，3 and 6 months of medication to the clinic. The levels of N-terminal pro-B-type natriuretic peptide （NT-proBNP）， soluble growth stimulation expressed gene 2 protein （sST2） and echocardiography indexes were compared between 2 groups before and after medication. The 6-minute walking test （6MWT）and the incidence of cardiogenic readmission events were recorded in 2 groups after medication. RESULTS ：Compared with before treatment，the indexes of the two groups were significantly improved at 1，3 and 6 months after treatment （P＜0.05）. Compared with control group ，the levels of NT-proBNP and sST 2 in ARNI group decreased significantly （P＜0.05），the levels of left ventricular ejection fraction and 6MWT increased significantly（P＜0.05），and the left ventricular end systolic diameter and left ventricular end diastolic diameter decreased significantly，after 3 and 6 months of treatm ent（P＜0.05）. However ，there was no significant difference in the velocity ratio of peak E to peak A ，pulmonary artery pressure ，right ventricular end diastolic diameter and the incidence of cardiogenic readmission events between 2 groups（P＞0.05）. CONCLUSIONS ：For patients with AAMI complicated with acute cardiac insufficiency ， compared with enalapril ，SVS can significantly improve the cardiac function （especially the left ventricular systolic function ）， reduce the inflammatory reaction of cardiomyocytes ，protect cardiomyocytes ，so as to improve the short-term prognosis of patients.

Pharmacological treatment of scleroderma renal crisis: A systematic literature review / Tratamiento farmacológico de la crisis renal en esclerosis sistémica: una revisión sistemática de la literatura

ABSTRACT Background: Scleroderma renal crisis is a condition that affects approximately 4-6% of patients with systemic sclerosis, especially with diffuse compromise. Clinical manifestations are variable, representing a diagnostic challenge. Objective: The study aims to describe and analyze the different pharmacological treatments available for the management of scleroderma renal crisis. Materials and methods: A systematic literature review was done based on observational studies and clinical trials about the treatment of scleroderma renal crisis, using monotherapy or combined therapy. The studies were identified using electronic scientific databases, including MEDLINE PUBMED and EMBASE, in English, published between January 1990 and August 2019. Results: Eleven studies were included (ten observational studies and one open clinical trial). Of them, seven were cohorts, one case series, and two case-control studies. Overall, 1113 patients were included in the analyzed studies. All studies used angiotensin-converting enzyme inhibitors as exposition, case definition, and/or comparison in the clinical trial. Regarding the need for dialysis, approximately 53.9% of patients required it temporarily or permanently. Approximately 6-27% of patients required temporal dialysis, and 19-78% required permanent dialysis. One-year survival range was between 64 and 84%; two-year survival was between 53 and 74%; five-year survival between 40 and 90%, and finally ten-year survival between 35 and 47%. Conclusions: Angiotensin-converting enzyme inhibitors continue to be the first line of treatment for scleroderma renal crisis by contributing to a decrease in short-term mortality. However, alternative therapeutic options are required as a high percentage of patients still require dialysis. Future clinical trials are necessary to assess the effectiveness and safety of different therapeutic options.

RESUMEN Introducción: La crisis renal es una condición que afecta aproximadamente a 4-6% de los pacientes con esclerosis sistémica, especialmente con compromiso difuso. Las manifestaciones clínicas son variables, representando un reto diagnóstico en la práctica clínica. Objetivo: El objetivo del estudio fue describir y analizar los diferentes tratamientos farmacológicos disponibles para el manejo de la crisis renal en esclerosis sistémica. Materiales y métodos: Una revisión sistemática de la literatura fue desarrollada con base en estudios observacionales y ensayos clínicos sobre el tratamiento de la crisis renal, utilizando monoterapia o terapias combinadas. Los estudios fueron identificados utilizando bases de datos científicas que incluyeron MEDLINE PUBMED y EMBASE, que estuvieran en inglés y publicados entre enero de 1990 y agosto de 2019. Resultados: Once estudios fueron incluidos (10 estudios observacionales y un ensayo clínico abierto). De estos, siete fueron cohortes, una serie de casos y dos estudios de casos y controles. En total, 1113 pacientes fueron incluidos en los estudios analizados. Todos los estudios utilizaron inhibidores de enzima convertidora de angiotensina como exposición, definición de caso y/o comparador en ensayo clínico. Sobre la necesidad de diálisis, aproximadamente 53,9% de los pacientes la requirieron de forma temporal o permanente. Aproximadamente 6-27% de pacientes requirieron diálisis temporal y 19-78% requirieron diálisis permanente. El rango de sobrevida al año fue de 64-84%; a dos arios 53-74%; a cinco arios 40-90%, y a diez arnos 35-47%. Conclusiones: Los inhibidores de enzima convertidora de angiotensina continúan siendo la primera línea de tratamiento de crisis renal en esclerosis sistémica, al contribuir en la reducción de la mortalidad a corto plazo. Sin embargo, opciones terapéuticas alternativas son requeridas, al continuar muy elevado el porcentaje de requerimiento de diálisis. Ensayos clínicos futuros son necesarios para evaluar la eficacia y seguridad de diferentes opciones terapéuticas.

Quality of life of patients receiving a single or combination of calcium channel blocker-angiotensin receptor blocker: A cross-sectional study in West Java, Indonesia

The prevalence of hypertension, based on the Indonesian Basic Health Research 2018, was 34.1%. Hypertensivepatients usually show a low quality of life (QoL) due to their lifelong drug dependence. This cross-sectional study wasconducted to determine the QoL of adult hypertensive patients treated with a single calcium channel blocker (CCB)and combination of CCB and angiotensin receptor blocker (ARB) at a primary referral hospital in West Java duringDecember 2018–February 2019. The QoL of the patients was determined using the Indonesian validated Euroqol 5dimensions 5 level and Euroqol visual analog scale questionnaires. 83 adult hypertensive outpatients were recruitedand agreed to participate in this study. Of the 83 hypertensive patients, 44.6% were being treated with a single CCBand 55.4% were being given the combination of CCB and ARB. The characteristics of the patients were as follows:the age was 51 ± 1.04 years, 71.3% were female, 84.3% were married, 66.2% never undertook physical activity, dailydrugs consumed 4 ± 0.19 items, and the duration of hypertensive therapy was 20 ± 3.3 months. Most of the patientsindicated problems in the area of pain and anxiety. The hypertensive patients treated with a combination of nifedipineand candesartan indicated the best QoL, whereas the lowest QoL was found in patients treated with a combination ofnifedipine and valsartan.

Recomendación rápida sobre el uso de antihipertensivos IECA/ARA II en pacientes con riesgo o documentación de COVID-19 / Rapid recommendation on the use of ACEI/ARA antihypertensives in patients at risk or with documented COVID-19

Ciertos hallazgos preclínicos generaron preocupación en la comunidad científica y en la población general sobre el uso de inhibidores de la enzima convertidora de angiotensina (IECA) y los antagonistas del receptor de la angiotensina II (ARAII), y los posibles desenlaces adversos asociados con relación a la infección por el nuevo Coronavirus (SARS-Cov-2).Por este motivo, nos planteamos como objetivo proveer de recomendaciones dinámicas (living recommendations) para el tratamiento con fármacos IECA o ARA II en pacientes con riesgo o documentación de infección por SARS-CoV-2 (en todo su espectro de gravedad). Se utilizó como metodología la adaptación/adopción de guías de práctica clínica bajo el enfoque GRADE, actualizando la evidencia al 7 de abril de 2020 mediante búsquedas en múltiples bases de datos y consultando a un panel multidisciplinario libre de conflictos de interés. Como resultado de este proceso se arribó a la siguiente afirmación: se recomienda, en contexto de la pandemia de COVID-19, en personas que se encuentran en tratamiento con IECA/ARAII, mantener el tratamiento sin cambios por sobre suspenderlo o reemplazarlo por otros fármacos (Recomendación fuerte a favor - calidad de evidencia baja). (AU)

Certain preclinical findings raised concerns in the scientific community and in the general population about the use ofangiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor antagonists (ARA) and the possible adverse outcomes associated with the infection with the new Coronavirus (SARS-Cov-2). For this reason, our objective is to provide living recommendations for treatment with ACEI or ARA in patients with risk or documentation of SARS-CoV-2 infection (inall its severity spectrum). The adaptation/adoption of clinical practice guidelines under the GRADE approach was used as a methodology, updating the evidence as of April 7, 2020, by searching multiple databases and consulting a multidisciplinary panel free of conflicts of interest. As a result of this process, the following statement was reached: it is recommended, in the context of the COVID-19 pandemic, in people who are undergoing treatment with ACEI/ARA, to maintain the treatment unchanged instead of its suspension or replacement with other drugs (Strong recommendation in favor - low quality ofevidence). (AU)

Effects of angiotensin II receptor blockers and angiotensin-converting enzyme inhibitors on COVID-19: a narrative review of the literature / Efectos de bloqueadores del receptor de angiotensina II e inhibidores de la enzima convertidora de angiotensina en COVID-19: una revisión narrativa de la literatura / Efeitos dos bloqueadores do receptor da angiotensina II e inibidores da enzima de conversão da angiotensina no COVID-19: uma revisão narrativa da literatura

Introduction: An outbreak of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is currently affec-ting worldwide. The association between this virus and the upregulation of Angiotensin-Converting Enzyme 2 (ACE2) has been suggested as a potential as an important factor in the development of Coronavirus Disease- 19 (COVID-19). Objective: To describe the relationship between some antihypertensive treatments and COVID-19. Methods: A research was conducted with the components of the PIO (Population, Intervention, Outcomes) strate-gy, including the literature of the last 20 years available in central PubMed, Web of Science, Scopus, and Embase databases. All relevant articles that assessed the epidemiological relationship between SARS-CoV-2 and hyperten-sion, the treatment and outcomes of the patients who have this comorbidity, as well as the relationship between the RAA axis and COVID-19 were included in the analysis. Results: A total of 292 items were found in the databases. After a thorough analysis, 17 papers were selected, including in vitro and in vivo tests, clinical trials, and epidemiological studies related to the topic analyzed. Conclusion: Due to the systemic benefits of antihypertensive drugs targeting the RAA axis, and the lack of eviden-ce of these treatments being a risk factor, It is not recommended to withdraw these medications from hypertensive patients infected with SARS-CoV 2, unless there is a clinical indication.

Introducción: el surgimiento y diseminación del coronavirus tipo 2 del síndrome respiratorio agudo severo (SARS-CoV-2), actualmente, afecta a la mayoría de los del mundo. La asociación entre este virus y la regulación positiva de la enzima convertidora de angiotensina 2 (ACE2) se ha sugerido como un factor potencial en el desarrollo de la enfermedad por coronavirus-19 (COVID- 19). Objetivo: describir la relación entre algunos tratamientos antihipertensivos y la COVID-19. Métodos: se revisaron los componentes de la estrategia PIO (población, intervención, resultados). Se incluyeron todos los artículos relevantes de los últimos 20 años disponibles en las bases de datos centrales PubMed, Web of Science, Scopus y Embase, que describen la relación epidemiológica entre SARS-CoV-2 e hipertensión, el tratamiento y el desenlace de los pacientes quienes tienen esta comor-bilidad, así como la relación entre el eje renina-angiotensina-aldosterona y COVID-19. Resultados: se encontraron inicialmente 292 artículos en las bases de datos, para finalmente seleccio-nar 17 artículos, incluyendo exámenes in vivo e in vitro, ensayos clínicos y estudios epidemiológicos relacionados con el tema analizado. Conclusión: debido a los beneficiosos efectos sistémicos del tratamiento antihipertensivo, cuyo blanco es el sistema renina-angiotensina- aldosterona, y a la falta de evidencia acerca de estos me-dicamentos en cuanto a la inducción de SARS-CoV-2, no se recomienda suspender o contraindicar el tratamiento con estos fármacos en pacientes hipertensos positivos para COVID-19, a menos que haya una indicación clínica

Introdução: Um surto de Síndrome Respiratória Aguda Grave Coronavirus 2 (SARS-CoV-2) está afe-tando atualmente em todo o mundo. A associação entre esse vírus e a suprarregulação da Enzima Conversora da Angiotensina 2 (ACE2) tem sido sugerida como um fator potencial importante no de-senvolvimento da Doença do Coronavírus-19 (COVID-19). Objetivo: Descrever a relação entre al-guns tratamentos anti-hipertensivos e COVID-19. Métodos: Foi realizada uma pesquisa com os com-ponentes da estratégia Population, Intervention, Resultados (PIR), incluindo a literatura dos últimos 20 anos disponível nas bases de dados centrais PubMed, Web of Science, Scopus e Embase. Todos os artigos relevantes que avaliaram a relação epide-miológica entre SARS-CoV-2 e hipertensão, o trata-mento e resultados dos pacientes que apresentam essa comorbidade, bem como a relação entre o eixo RAA e COVID-19 foram incluídos na análise. Resultados: Foram encontrados 292 itens nas bases de dados. Após análise aprofundada, foram selecionados 17 artigos, entre testes in vitro e in vivo, en-saios clínicos e estudos epidemiológicos relacionados ao tema analisado. Conclusão: Devido aos be-nefícios sistêmicos dos medicamentos anti-hipertensivos direcionados ao eixo RAA e à falta de evi-dência desses tratamentos serem um fator de risco, não é recomendado retirar esses medicamentos de pacientes hipertensos infectados com SARS-CoV 2, a menos que haja um indicação clínica.