Background: Hypertension is a major public health problem in both developing and developed nations because it is highly prevalent and is associated with complications. Numerous enviromnental and genetic variables are linked to the occurrence of the disease. It may be influenced by the renin-angiotensin-aldosterone system, M'hich preserves bodily homeostasis. The angiotensinogen gene 11235T polymorphisms that has an effect on the activity of the renin-angiotensin-aldosterone system are related to the high hvpertension risk. The aim of this study was to find out the association between angiotensinogen Nf235T gene polymorphism and the risk of developing hypertenMon. Methods: A total of 306 samples - 153 patients Il'ith hvpertension and 153 age- and ser-matched healthy controls were selected using a simple random sampling technique. Clinical and biochemical variables were measured to assess the associated riskfactors. Blood samples from the patients and matched controls were used to isolate deoxyribonucleic acid. The AGT 11235T genotypes u:ere identified using polymerase chain reaction and analyzed by agarose gel electrophoresis. Logistic regression with a 95% confidence interval (CI) was employed to assess the risk correlations ofAGT gene M235Tpolymorphisms with hypertension. Results: Our analysis showed that the AGT-TT genotype (odds ratio [OR] = 3.11, 95% CL = 1.675.79, P< 0.001) and T allele (OR = 2.18, 95% CL = 1.563.04, P< 0.001) are considerably higher in hypertensive patients than in healthy controls. Our study also identified the clinical risk factors for hypertension, such as, total cholesterol, triglycerol, low density lipoprotein-cholesterol, and high density lipoprotein-cholesterol Inels, which were significantly higher in patients compared to controls (P< 0.001). Conclusion: The A GT M235T genes of the TT genotype and the T allele are associated with an increased risk of hypertension among the Ethiopian patients. A population-based epidemiological study is needed corroborate the association between AGT and HTN
Subject(s)Humans , Renin-Angiotensin System , Angiotensinogen , Blood Pressure , Risk Factors , GB virus C , Hypertension
Abstract Introduction Coronavirus disease 2019 (COVID-19) may present with extrapulmonary manifestations, including hematologic changes. Previous studies suggest that severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) can interact with the renin-angiotensin system, ultimately causing increased production of angiotensin II. By reporting the cases of previously healthy young adults diagnosed with a hematologic malignancy after experiencing COVID-19, we raise the hypothesis that the SARS-Cov-2 infection could act as a trigger for leukemogenesis in predisposed individuals. Methods This was a case series performed through extraction of relevant clinical information from the medical records of three patients admitted to our Hematology unit between August 2020 and September 2020. Main Results Considering the relatively rapid development of cytopenias following recovery from COVID-19, it cannot be ruled out that SARS-Cov-2 played a role in leukemogenesis in those patients. Based on previous in vitro studies, the renin-angiotensin system imbalance induced by SARS-CoV-2 could potentially promote in vivo leukemogenesis through several mechanisms. Conclusion Despite the advances in pathophysiological and clinical characterization of COVID-19, the consequences of the pandemic to the incidence of hematologic diseases are still to be elucidated. In this context, future dissection of the status of the local bone marrow renin-angiotensin system in leukemogenesis is a clinically relevant basic research area.
Subject(s)Humans , Male , Female , Adult , Hematologic Neoplasms , COVID-19 , Renin-Angiotensin System , Leukemia , SARS-CoV-2
Consecutively hospitalized patients with confirmed coronavirus disease 2019 (COVID-19) in Wuhan, China were retrospectively enrolled from January 2020 to March 2020 to investigate the association between the use of renin-angiotensin system inhibitor (RAS-I) and the outcome of this disease. Associations between the use of RAS-I (angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB)), ACEI, and ARB and in-hospital mortality were analyzed using multivariate Cox proportional hazards regression models in overall and subgroup of hypertension status. A total of 2771 patients with COVID-19 were included, with moderate and severe cases accounting for 45.0% and 36.5%, respectively. A total of 195 (7.0%) patients died. RAS-I (hazard ratio (HR)= 0.499, 95% confidence interval (CI) 0.325-0.767) and ARB (HR = 0.410, 95% CI 0.240-0.700) use was associated with a reduced risk of all-cause mortality among patients with COVID-19. For patients with hypertension, RAS-I and ARB applications were also associated with a reduced risk of mortality with HR of 0.352 (95% CI 0.162-0.764) and 0.279 (95% CI 0.115-0.677), respectively. RAS-I exhibited protective effects on the survival outcome of COVID-19. ARB use was associated with a reduced risk of all-cause mortality among patients with COVID-19.
Subject(s)Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , COVID-19 , Humans , Hypertension/drug therapy , Renin-Angiotensin System , Retrospective Studies
The renin angiotensin system (RAS) appears to influence male fertility at multiple levels. In this work, we analyzed the relationship between the RAS and DNA integrity. Fifty male volunteers were divided into two groups (25 each): control (DNA fragmentation ≤20%) and pathological (DNA fragmentation >20%) cases. Activities of five peptidases controlling RAS were measured fluorometrically: prolyl endopeptidase (which converts angiotensin [A] I and A II to A 1-7), neutral endopeptidase (NEP/CD10: A I to A 1-7), aminopeptidase N (APN/CD13: A III to A IV), aminopeptidase A (A II to A III) and aminopeptidase B (A III to A IV). Angiotensin-converting enzyme (A I to A II), APN/CD13 and NEP/CD10 were also assessed by semiquantitative cytometry and quantitative flow cytometry assays, as were the receptors of all RAS components: A II receptor type 1 (AT1R), A II receptor type 2 (AT2R), A IV receptor (AT4R or insulin-regulated aminopeptidase [IRAP]), (pro)renin receptor (PRR) and A 1-7 receptor or Mas receptor (MasR) None of the enzymes that regulate levels of RAS components, except for APN/CD13 (decrease in fragmented cells), showed significant differences between both groups. Micrographs of RAS receptors revealed no significant differences in immunolabeling patterns between normozoospermic and fragmented cells. Labeling of AT1R (94.3% normozoospermic vs 84.1% fragmented), AT4R (96.2% vs 95.3%) and MasR (97.4% vs 87.2%) was similar between the groups. AT2R (87.4% normozoospermic vs 63.1% fragmented) and PRR (96.4% vs 48.2%) were higher in non-fragmented spermatozoa. These findings suggest that fragmented DNA spermatozoa have a lower capacity to respond to bioactive RAS peptides.
Subject(s)Angiotensins , DNA Fragmentation , Humans , Insulin , Male , Renin-Angiotensin System/physiology , Spermatozoa
INTRODUÇÃO: Os contraceptivos orais são a forma mais utilizada para o controle de natalidade, chegando a 200 milhões de usuárias desde sua iniciação na década de 1960. Desde 2013, nosso grupo de pesquisa tem apresentado resultados que sugerem que mulheres em uso de Contraceptivos Orais Combinados (COC), e sem outros fatores de risco, apresentam maior valor de proteína C reativa, lipemia pós-prandial, lipoproteína de baixa densidade oxidada e diminuição da sensibilidade insulínica, quando comparadas a suas congêneres sem uso de COC. Recentemente, foi verificado que o uso de COC eleva os valores de renina plasmática em 600%, podendo explicar por que o uso desse fármaco é um fator de risco para o desenvolvimento de hipertensão arterial sistêmica. Apesar de o uso de Contraceptivo Hormonal Injetável (CHI) estar aumentando, não encontramos estudos clínicos que abordassem o tema, demonstrando uma lacuna na literatura científica. OBJETIVO: Comparar os valores de renina plasmática, enzima conversora de angiotensina 1 e aldosterona de mulheres que utilizam CHI com mulheres que não utilizam nenhum contraceptivo à base de hormônio. MÉTODOS: Protocolo de um estudo observacional comparativo de corte transversal, composto por mulheres com idade entre 18 e 30 anos, eutróficas, irregularmente ativas pelo Questionário Internacional de Atividade Física, versão curta, que estão em uso continuado de CHI há pelo menos 6 meses ou que não fazem uso. A amostra será por conveniência, as participantes selecionadas assinarão o termo de consentimento livre e esclarecido. Posteriormente, responderão a um questionário padrão, serão submetidas a um exame físico, e serão encaminhadas para coleta das amostras sanguíneas.
INTRODUCTION: Oral contraceptives are the most widely used form of birth control, reaching 200 million users since its inception in the 1960. Since 2013, our research group has presented results that suggest that women using Combined Oral Contraceptives (COC) and without other risk factors, have a higher value of C-reactive protein, postprandial lipemia, oxidized low-density lipoprotein and decreased insulin sensitivity, when compared to their counterparts without the use of COC. Recently, it was found that the use of COC increases plasma renin values by 600%, which may explain why the use of this drug is a risk factor for the development of systemic arterial hypertension. Although the use of Injectable Hormonal Contraceptives (IHC) is increasing, we have not found clinical studies that addressed the topic, demonstrating a gap in the scientific literature. OBJECTIVE: Compare the values of plasma renin, angiotensin-converting enzyme 1 and aldosterone of women using IHC with women who do not use any hormone-based contraceptives. METHODS: Protocol of a comparative observational cross-sectional study, composed of women aged between 18 and 30 years, eutrophic, irregularly active by the International Physical Activity Questionnaire, short version, who have been in continuous use of IHC for at least 6 months or that do not use. The sample will be for convenience and the selected participants will sign the informed consent form. Subsequently, they will answer a standard questionnaire, undergo a physical examination, and be sent to collect blood samples.
Subject(s)Renin-Angiotensin System , Women's Health , Hypertension
No combate à infecção pelo coronavírus 2 da síndrome respiratória aguda grave (SARS-CoV-2), o organismo se utiliza de mecanismos da imunidade inata, dentre eles os receptores Toll- Like (TLR), responsáveis pela sinalização da inflamação através da liberação de mediadores químicos e recrutamento de células imunitárias. Na patologia causada pela doença do SARS-CoV-2 2019 (COVID-19), ganha especial importância o TLR-4, visto que a sua estimulação exacerbada vem sendo relacionada ao estado hiperinflamatório em fases avançadas da COVID-19. Outro receptor que desempenha um papel primordial na infecção pelo SARS-CoV-2, servindo como porta de entrada para o vírus e progressão da doença, é a enzima conversora de angiotensina 2 (ECA 2), cuja ligação com a proteína S viral causa desregulação de vários sistemas fundamentais para a homeostase, como o sistema renina-angiotensina-aldosterona. Pacientes com doenças cardiometabólicas como obesidade, diabetes, aterosclerose e hipertensão vêm sendo classificados como alto risco para desenvolver as formas graves da COVID-19, visto que o estado inflamatório, já existente nessas doenças, pode ser agravado pelo desequilíbrio metabólico causado pelo SARS-CoV-2. A elucidação desses e de outros mecanismos relacionados à fisiopatologia da COVID-19 é imprescindível para uma melhora na estratificação de risco, nas escolhas terapêuticas e no prognóstico desses pacientes. Desta forma, nesta revisão objetivamos discutir as relações entre TLR-4, ECA 2, doenças cardiometabólicas, infecção pelo SARS-CoV-2 e gravidade da COVID-19.
In the fight against the infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the body uses mechanisms from the innate immune system, such as Toll-Like receptors (TLR), responsible for inflammation signaling through release of chemical mediators and recruitment of immune cells. In the disease caused by SARS-CoV-2 (COVID-19), TLR-4 assumes special importance because its exacerbated stimulation has been related to a hyperinflammatory state in advanced stages of COVID-19. Another receptor that plays a major role in SARS-CoV-2 infection, serving as a gateway to the virus and impacting disease progression, is angiotensin-converting enzyme 2 (ACE-2), whose binding to the viral S protein causes dysregulation of several key systems for homeostasis, such as the renin-angiotensin-aldosterone system. The elucidation of these and other mechanisms related to the pathophysiology of COVID-19 is essential for an improvement in risk stratification, therapeutic choices, and prognosis for these patients. Thus, we aimed to discuss in this review the relationships between TLR-4, ACE-2, cardiometabolic diseases, SARS-CoV-2 infection, and severity of COVID-19.
Subject(s)Humans , Diabetes Mellitus , Atherosclerosis , Toll-Like Receptors , Angiotensin-Converting Enzyme 2 , SARS-CoV-2 , COVID-19 , COVID-19/physiopathology , Hypertension , Obesity , Pathology , Patients , Prognosis , Renin-Angiotensin System , Therapeutics , Viruses , Immune System
O objetivo deste trabalho é reunir e discutir os principais achados científicos, opiniões de especialistas e considerações de comunidades médicas a respeito da continuação do tratamento de pacientes hipertensos diagnosticados com Covid-19 em uso de anti-hipertensivos. Trata-se de uma revisão narrativa de literatura, restringida a publicações até abril de 2020, utilizando as bases de dados Medline e Embase e consulta a quatro sociedades científicas de Cardiologia. Um total de 93 publicações foram encontradas nas bases de dados consultadas, e, destas, nove publicações foram elegíveis para análise, sendo que seis publicações se mostraram favoráveis à continuação do tratamento com inibidores da enzima conversora de angiotensina e antagonistas dos receptores de angiotensina, o que foi ao encontro das recomendações das sociedades de Cardiologia; outras três publicações sugeriram que essas classes de anti-hipertensivos podem aumentar a gravidade da infecção. A continuação do tratamento com anti-hipertensivos durante a pandemia de coronavírus ou após o diagnóstico da infecção apresenta um paradoxo entre o potencial aumento da patogenicidade viral e a proteção pulmonar conferida pelo equilíbrio do sistema renina-angiotensina.
The objective of this work is to gather and discuss the main scientific findings, opinions and specialists in medical communities and respect for the continuation of treatment with antihypertensive drugs in hypertensive patients diagnosed with Covid-19. This is a narrative review of the literature, restricted to publications until April 2020, using Medline and Embase as a database and consulting four scientific societies of cardiology. A total of 93 publications were found in the databases consulted and of these, 9 publications were eligible for analysis, with six publications being considered favorable for the continuation of treatment with angiotensin-converting enzyme inhibitors and receptor antagonists angiotensin, which met the decisions of cardiology societies; three other publications suggested that these classes of antihypertensives may increase the severity of the infection. The continuation of treatment with antihypertensive drugs during a coronavirus pandemic or after the diagnosis of infection presents a paradox between the potential increase in viral pathogenicity and the pulmonary protection provided by the balance of the renin-angiotensin system.
Subject(s)Humans , Male , Female , Renin-Angiotensin System , Angiotensin-Converting Enzyme Inhibitors , Coronavirus Infections , Betacoronavirus , Hypertension , Antihypertensive Agents
Subject(s)Renin-Angiotensin System , COVID-19
OBJECTIVE@#Cardiovascular diseases are associated with an increased risk of depression, but it remains unclear whether treatment with cardiovascular agents decreases or increases this risk. The effects of drugs on individual usage are also often unknown. This review aimed to examine the correlation between depression and common cardiovascular drugs, develop more potent interventions for depression in cardiovascular patients, and further research on the bio-behavioural mechanisms linking cardiovascular drugs to depression.@*DATA SOURCES@#The data in this review were obtained from articles included in PubMed, EMBASE, and Web of Science.@*STUDY SELECTION@#Clinical trials, observational studies, review literature, and guidelines about depression and cardiovascular drugs were selected for the article.@*RESULTS@#We systematically investigated whether the seven most used cardiovascular drugs were associated with altered risk of incident depression in this literature review. Statins have been proven to have antidepressant effects. Some studies believe angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blocker (ARB) can exert an antidepressant influence by acting on the renin-angiotensin system, but further clinical trials are needed to confirm this. Beta-blockers have previously been associated with depression, but the current study found no significant association between beta blockers and the risk of depression. Aspirin may have antidepressant effects by suppressing the immune response, but its role as an antidepressant remains controversial. calcium channel blockers (CCBs) can regulate nerve signal transduction by adjusting calcium channels, but whether this effect is beneficial or harmful to depression remains unclear. Finally, some cases have reported that nitrates and diuretics are associated with depression, but the current clinical evidence is insufficient.@*CONCLUSIONS@#Statins have been proven to have antidepressant effect, and the antidepressant effects of ACEIs/ARB and aspirin are still controversial. CCBs are associated with depression, but it is unclear whether it is beneficial or harmful. No association has been found with β-blockers, diuretics, and nitrates.
Subject(s)Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Antihypertensive Agents/therapeutic use , Calcium Channel Blockers/therapeutic use , Cardiovascular Agents/therapeutic use , Cardiovascular Diseases/drug therapy , Depression/drug therapy , Humans , Hypertension/drug therapy , Renin-Angiotensin System
Diante do contexto pandêmico da COVID-19, esforços têm sido direcionados ao desenvolvimento de medidas terapêuticas seguras e eficazes no combate à doença. Entretanto, divergências entre as condutas adotadas nesses pacientes tem sido frequentes. Em especial, fármacos inibidores do Sistema Renina-Angiotensina, como os Inibidores da Enzima Conversora de Angiotensina e Bloqueadores do Receptor da Angiotensina, são foco de grande discussão. Diversos autores questionam uma possível relação de risco aumentado entre o uso de tais medicações e o desenvolvimento de formas mais graves da doença, ao correlacionar a regulação positiva da Enzima Conversora de Angiotensina 2 induzida por esses fármacos com o fato do SARS-CoV-2 usar essa enzima como receptor celular. Enquanto isso, outros autores defendem que essa modulação atue como fator protetor à gravidade da infecção, levando em consideração a promoção de efeitos vasodepressores, anti-fibróticos e anti-inflamatórios. Dada a alta prevalência do uso desses anti-hipertensivos, a presente revisão analisa o funcionamento do Sistema Renina-Angiotensina; aspectos moleculares do novo coronavírus; e a inibição da Angiotensina 2 no contexto dessa infecção, para discutir qual conduta seria mais adequada no manejo da hipertensão arterial e doenças cardiovasculares, dada a pandemia da COVID-19.
In the face of the pandemic context of the COVID-19, efforts have been directed to the development of safe and effective therapeutic actions in combating the disease. However, divergences between management of these patients have been frequent. Especially, Renin-Angiotensin System inhibitors, as Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers, are the focus of great discussion. Several authors question a possible increased risk relation between the use of that medication and the development of the most severe disease form, when correlating AngiotensinConverting Enzyme 2 upregulation induced by those drugs with the fact that SARS-CoV-2 uses this enzyme as its cellular receptor. Meanwhile, other authors defend that the referred modulation acts as a protective factor to infection severity, considering the induction of vasodepressor, antifibrotic and anti-inflammatory effects. Given the high prevalence of the use of those antihypertensive drugs, the present review analyses the Renin-Angiotensin System functionning; molecular aspects of the novel coronavirus; and the Angiotensin 2 inhibition in the context of this infection, in order to discuss which conduct would be more appropriate in the management of arterial hypertension and cardiovascular diseases, given the COVID-19 pandemic.
Subject(s)Humans , Renin-Angiotensin System , Angiotensin-Converting Enzyme Inhibitors , Coronavirus Infections , Cardiovascular Agents , Angiotensin II Type 1 Receptor Blockers , Hypertension
Among the multiple uncertainties surrounding the novel coronavirus disease (COVID-19) pandemic, a research letter published in The Lancet implicated drugs that antagonize the renin-angiotensin-aldosterone system (RAAS) in an unfavorable prognosis of COVID-19. This report prompted investigations to identify mechanisms by which blocking angiotensin-converting enzyme 2 (ACE2) could lead to serious consequences in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The possible association between RAAS inhibitors use and unfavorable prognosis in this disease may have been biased by the presence of underlying cardiovascular diseases. As the number of COVID-19 cases has increased worldwide, it has now become possible to investigate the association between RAAS inhibitors and unfavorable prognosis in larger cohorts. Observational studies and one randomized clinical trial failed to identify any consistent association between the use of these drugs and unfavorable prognosis in COVID-19. In view of the accumulated clinical evidence, several scientific societies recommend that treatment with RAAS inhibitors should not be discontinued in patients diagnosed with COVID-19 (unless contraindicated). This recommendation should be followed by clinicians and patients.
Subject(s)Humans , Coronavirus , COVID-19 , Renin-Angiotensin System , Angiotensin-Converting Enzyme Inhibitors/adverse effects , Randomized Controlled Trials as Topic , Peptidyl-Dipeptidase A/metabolism , Angiotensin Receptor Antagonists/adverse effects , SARS-CoV-2
SUMMARY Severe Acute Respiratory Syndrome Coronavirus 2 is part of the Cononaviridae family and is the causative agent of the 2019 (Covid-19) Coronavirus pandemic declared by the World Health Organization in March, 2020. This virus has a high rate of transmission, affecting several individuals, and has caused thousands of deaths. The clinical manifestations of Severe Acute Respiratory Syndrome Coronavirus 2 infection are not restricted only to the respiratory tract, and there is an express involvement of the cardiovascular system with a higher risk of death in this group. In such patients there is an overactivation of renin-angiotensin-aldosterone system, which promotes an increase in the expression of angiotensin-converting enzyme - 2 that acts as a receptor for the SPIKE protein expressed by the virus and enables the interaction between the host cell and Severe Acute Respiratory Syndrome Coronavirus 2. This process of infection causes a hyperinflammatory state that increases the inflammatory markers of cardiac injury. Hence, an adequate understanding and clinical guidance regarding the monitoring, and controlling the damage in these patients is essential to avoid worsening of their clinical condition and to prevent death.
Subject(s)Humans , Cardiovascular System , COVID-19 , Renin-Angiotensin System , Pandemics , SARS-CoV-2
Subject(s)Humans , Renin-Angiotensin System , Coronavirus Infections , Psychomotor Agitation , Angiotensins , Renin , Colombia , Aldosterone
Resumen El nuevo coronavirus SARS-CoV-2, causante de la enfermedad COVID-19, presenta una alta mortalidad en pacientes con enfermedades cardiovasculares, diabetes e hipertensión, trastornos que comparten la fisiopatología subyacente relacionada con el sistema renina-angiotensina (RAS). El SARS-CoV-2 utiliza la proteína de la membrana angiotensina I y convierte a la enzima convertidora de angiotensina tipo 2 (ACE2) en un receptor de entrada celular; por tanto, el RAS, regulado por ACE y ACE2, puede verse alterado en pacientes con COVID-19. Sin embargo, aún no es claro si el uso de fármacos antihipertensivos inhibidores de la ACE2 y bloqueadores del receptor de angiotensina II podría potencializar el daño ocasionado por el virus o contrarrestar su efecto, sobre todo a nivel pulmonar. El desafío se ve agravado por la información exagerada publicada en diferentes revistas científicas, la cual podría llevar a acciones inapropiadas, por lo que es importante diferenciar rápidamente la verdadera epidemia de hipótesis falsas, que podría llevar a conductas medicas potencialmente dañinas.
Abstract The new coronavirus SARS-CoV-2, which causes the disease COVID-19, has a high mortality in patients with cardiovascular diseases, diabetes and hypertension, disorders that share the underlying pathophysiology related to the renin-angiotensin system (RAS). SARS-CoV-2 uses the membrane protein angiotensin I and converts angiotensin converting enzyme type 2 (ACE2) into a cellular entry receptor, therefore, RAS, regulated by ACE and ACE2, can be altered in COVID-19 patients. However, it is not yet clear whether the use of antihypertensive drugs ACE2 inhibitors and angiotensin II receptor blockers could potentiate the damage caused by the virus or counteract its effect, especially in the lungs. The challenge is compounded by the exaggerated information published in different scientific journals, which could lead to inappropriate actions, so it is important to quickly differentiate the true epidemic from false hypotheses, which could lead to potentially harmful medical behaviors.
Subject(s)Humans , Male , Female , Cardiovascular Diseases , COVID-19 , Patients , Renin-Angiotensin System , Colombia , Epidemics , Pulmonary Arterial Hypertension
The new SARS-CoV2 pandemic has ignited research worldwide, regarding its parameters. Hypertension, a comorbidity with high prevalence among patients with COVID-19 infection, is being extensively studied in the setting of the pandemic. Futhermore, RAAS inhibitors, drugs widely used among hypertensive patients, are on the spotlight regarding their safety during the COVID-19 era. In this review, we present current knowledge regarding both these aspects, as well as the new guidelines for the treatment of hypertensive patients during the pandemic
Subject(s)Humans , Renin-Angiotensin System , SARS-CoV-2/immunology , COVID-19/therapy , Hypertension/therapy
Abstract As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients with hypertension and other cardiovascular comorbidities develop more severe coronavirus disease (COVID)-19 and are at high risk of death, a controversy arose about the use of antihypertensives as angiotensin-converting enzyme inhibitors (ACEis) and angiotensin II receptor blockers (ARBs). Such drugs might increase the expression of the fundamental receptor of this new infectious agent: the angiotensin-converting enzyme 2 (ACE2). Preclinical observations indicate that the increase of ACE2 expression or the activity by ACEis and ARBs leads to a greater transformation of angiotensin (Ang)-II to Ang-(1-7), which is associated with positive effects on cardiovascular and pulmonary pathophysiology. This association has been demonstrated in observational studies in patients with cardiovascular pathology and pneumonia. It has not been possible to confirm whether users of ACEis or ARBs are more infected by the new coronavirus, due to methodological issues in studies with patients infected with SARS-CoV-2. However, the use of such antihypertensive treatments in both children and adults might reduce the virulence of infection. Therefore, changes in the antihypertensive therapy of patients at risk of contracting COVID-19 are not recommended.
Resumen Los pacientes con hipertensión y otra comorbilidad cardiovascular infectados con SARS-CoV-2 desarrollan cuadros más graves de COVID-19 y con mayor frecuencia fallecen. Este hecho ha originado una controversia acerca del uso de antihipertensivos inhibidores de la enzima convertidora de la angiotensina (IECA) y de antagonistas de los receptores de la angiotensina II (ARA-II), pues tales medicamentos pueden incrementar la expresión del receptor funcional de este nuevo agente infeccioso: la enzima convertidora de la angiotensina 2 (ECA2). Las observaciones preclínicas indican que el aumento de la expresión o de la actividad de la ECA2 por uso de IECA o ARA-II conduce a una mayor transformación de angiotensina 2 a a angiotensina 1-7, la cual se asocia con efectos positivos sobre la fisiopatología pulmonar y cardiovascular. En estudios observacionales de pacientes con patología cardiovascular y neumonía se ha confirmado esta asociación. La falta de evidencia contundente debida a aspectos metodológicos en estudios con pacientes infectados con SARS-CoV-2 no permite confirmar si los usuarios de IECA o ARA-II se contagian más con el nuevo coronavirus. Sin embargo, continuar con tales medicamentos antihipertensivos, tanto en adultos como en niños, podría reducir la virulencia de la infección. Por ello, no se recomienda cambiar la terapia antihipertensiva en los pacientes susceptibles a la COVID-19.
Subject(s)Adult , Animals , Child , Humans , Pneumonia, Viral/virology , Coronavirus Infections/virology , Betacoronavirus/isolation & purification , Antihypertensive Agents/administration & dosage , Pneumonia, Viral/mortality , Pneumonia, Viral/drug therapy , Renin-Angiotensin System/drug effects , Angiotensin-Converting Enzyme Inhibitors/administration & dosage , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Risk Factors , Coronavirus Infections/mortality , Coronavirus Infections/drug therapy , Angiotensin Receptor Antagonists/administration & dosage , Angiotensin Receptor Antagonists/pharmacology , Pandemics , SARS-CoV-2 , COVID-19 , Hypertension/drug therapy , Antihypertensive Agents/pharmacology
ABSTRACT Introduction: The Renin-Angiotensin-Aldosterone System (RAAS) has been suggested as a possible marker of renal injury in chronic diseases. This study proposes to analyze the serum and urinary markers of the RAAS in myelomeningocele patients with renal function abnormalities detected on DMSA. Material and Methods: Seventeen patients followed in our institution that presented with renal injury on DMSA. We review nephrologic and urologic clinical aspects and evaluated ultrassonagraphy, voiding urethrocystography and urodynamics. Urinary and serum samples were collected to evaluate possible correlations of renal lesions with RAAS. Control group urine and serum samples were also sent for analysis. Results: Serum ACE 2 activity means in relation to urodynamic findings were the only values that had a statistically significant difference (p = 0.040). Patients with normal bladder pattern presented higher ACE 2 levels than the high risk group. Statistical analysis showed that the study group (SG) had a significantly higher mean serum ACE than the CG. The means of ACE 2 and urinary ACE of the SG and CG were not statistically different. The ROC curve for serum ACE values had a statistically significant area for case and non-case differentiation, with 100% sensitivity and 53% specificity for values above 60.2 mg/dL. No statistically significant areas were observed in relation to ACE 2 and urinary ACE values between SG and CG. Conclusion: The analysis of serum ACE, ACE 2 and urinary ACE were not significant in patients with myelomeningocele and neurogenic bladder with renal injury previously detected by renal DMSA.
Subject(s)Humans , Renin-Angiotensin System , Meningomyelocele/complications , Meningomyelocele/metabolism , Succimer/metabolism , Kidney
O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referentes ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 12 artigos e 4 protocolos.
Subject(s)Humans , Pneumonia, Viral/drug therapy , Coronavirus Infections/drug therapy , Betacoronavirus/drug effects , Renin-Angiotensin System , Technology Assessment, Biomedical , Dexamethasone/therapeutic use , Vaccines/therapeutic use , Chloroquine/therapeutic use , Interferons/therapeutic use , Adrenal Cortex Hormones/therapeutic use , Azithromycin/therapeutic use , Heparin, Low-Molecular-Weight/therapeutic use , Ritonavir/therapeutic use , Drug Combinations , Interleukin 1 Receptor Antagonist Protein/therapeutic use , Lopinavir/therapeutic use , Rituximab/therapeutic use , Hydroxychloroquine/therapeutic use
Resumen La evidencia actual es limitada para determinar el impacto del uso de los inhibidores de la enzima convertidora de angiotensina (IECA) en la predisposición al empeoramiento de la enfermedad del coronavirus 2019 (COVID-19). Inicialmente se reportó que en los pacientes con progresión grave de la COVID-19 existía una mortalidad elevada, los cuales tenían antecedentes de hipertensión arterial, diabetes mellitus, enfermedad cardiovascular y enfermedad renal crónica. Parte de estos pacientes también tenía en común que utilizaban IECA, lo cual alertó a la comunidad médica sobre su riesgo potencial en coexistencia con COVID-19. Sin embargo, estudios más recientes de casos-controles encontraron que los inhibidores del sistema renina-angiotensina, incluyendo los IECA, no incrementan el riesgo de COVID-19 o de requerir admisión hospitalaria por esta causa. Diferentes revistas científicas han facilitado el acceso a reportes preliminares, dejando a discreción de la comunidad médica y científica hacer uso de dicha información para promover el desarrollo de estudios que confirmen experimentalmente dichos hallazgos, preclínicos y epidemiológicos, que finalmente impacten en las decisiones de la práctica clínica para beneficiar a los pacientes con COVID-19. En esta revisión de la literatura se exploran los diferentes efectos mediados por los IECA que podrían estar relacionados con la respuesta inmune durante la infección y la transmisión de COVID-19, compilando evidencia disponible que evalúa si en realidad representan un riesgo o si, por el contrario, confieren un efecto protector.
Abstract There is limited evidence for determining the impact of the use of angiotensin converting enzyme inhibitors (ACE-I) in the tendency to worsening of coronavirus-19 disease (COVID-19). It was initially reported that, in patients with serious progression of COVID-19, there was an increased mortality in those that had a history of suffering arterial hypertension, diabetes mellitus, cardiovascular disease, and chronic kidney disease. A proportion of these patients also had in common that they used ACE-I, which alerted the medical community on the potential risk in coexisting with COVID-19. However, in more recent case-control studies, they found that inhibitors of the renin-angiotensin system, including ACE-I, does not increase the risk of COVID-19 or require hospital admission due to this cause. Several scientific journals have provided access to preliminary reports, leaving the use of such information at the discretion of the medical and scientific community for promoting the development of studies that might confirm these preclinical and epidemiological findings experimentally. These may finally have an impact on the clinical practice decisions, in order to benefit patients with COVID-19. In this literature review, the different effects mediated by ACE-I that could be related to the immune response during the infection and transmission of COVID-19 are examined, gathering available evidence that evaluates whether, in reality, they represent a risk or if on the other hand, they confer a protector effect.