Renin-angiotensin system: Basic and clinical aspects-A general perspective.

The renin-angiotensin system (RAS) is one of the most complex hormonal regulatory systems, involving several organs that interact to regulate multiple body functions. The study of this system initially focused on investigating its role in the regulation of both cardiovascular function and related pathologies. From this approach, pharmacological strategies were developed for the treatment of cardiovascular diseases. However, new findings in recent decades have suggested that the RAS is much more complex and comprises two subsystems, the classic RAS and an alternative RAS, with antagonistic effects that are usually in equilibrium. The classic system is involved in pathologies where inflammatory, hypertrophic and fibrotic phenomena are common and is related to the development of chronic diseases that affect various body systems. This understanding has been reinforced by the evidence that local renin-angiotensin systems exist in many tissue types and by the role of the RAS in the spread and severity of COVID-19 infection, where it was discovered that viral entry into cells of the respiratory system is accomplished through binding to angiotensin-converting enzyme 2, which is present in the alveolar epithelium and is overexpressed in patients with chronic cardiometabolic diseases. In this narrative review, preclinical and clinical aspects of the RAS are presented and topics for future research are discussed some aspects are raised that should be clarified in the future and that call for further investigation of this system.

A novel cluster detection of COVID-19 patients and medical disease conditions using improved evolutionary clustering algorithm star.

With the increasing number of samples, the manual clustering of COVID-19 and medical disease data samples becomes time-consuming and requires highly skilled labour. Recently, several algorithms have been used for clustering medical datasets deterministically; however, these definitions have not been effective in grouping and analysing medical diseases. The use of evolutionary clustering algorithms may help to effectively cluster these diseases. On this presumption, we improved the current evolutionary clustering algorithm star (ECA*), called iECA*, in three manners: (i) utilising the elbow method to find the correct number of clusters; (ii) cleaning and processing data as part of iECA* to apply it to multivariate and domain-theory datasets; (iii) using iECA* for real-world applications in clustering COVID-19 and medical disease datasets. Experiments were conducted to examine the performance of iECA* against state-of-the-art algorithms using performance and validation measures (validation measures, statistical benchmarking, and performance ranking framework). The results demonstrate three primary findings. First, iECA* was more effective than other algorithms in grouping the chosen medical disease datasets according to the cluster validation criteria. Second, iECA* exhibited the lower execution time and memory consumption for clustering all the datasets, compared to the current clustering methods analysed. Third, an operational framework was proposed to rate the effectiveness of iECA* against other algorithms in the datasets analysed, and the results indicated that iECA* exhibited the best performance in clustering all medical datasets. Further research is required on real-world multi-dimensional data containing complex knowledge fields for experimental verification of iECA* compared to evolutionary algorithms.

Considerations on the use of antihypertensive blockers of the renin-angiotensin system in adults and children in the face of the COVID-19 pandemic.

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.

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.

[Comparative analysis between the use of renin-angiotensin system antagonists and clinical outcomes of hospitalized patients with COVID-19 respiratory infection]. / Análisis de la relación entre los inhibidores del sistema renina-angiotensina y la evolución de pacientes hospitalizados por infección respiratoria COVID-19.

INTRODUCTION: Hypertension has been associated with worse outcomes in patients with COVID-19 infection, so concerns have been raised about the possibility that inhibitors of the renin-angiotensin system (RAS) could influence the prognosis of these patients. METHODS: This is an observational study of 921 consecutive patients admitted with COVID-19 respiratory infection to Hospital General Universitario Ciudad Real from March 1 to April 30, 2020. Following data were collected including patient demographic information, medical history, clinical characteristics, laboratory data, therapeutic interventions during the hospitalization and clinical outcomes. RESULTS: The mean age was 78years, and 59.2% of patients had a history of hypertension. Patients with previous treatment with RAS inhibitor (42.4%) showed lower risk of the primary composite endpoint (mortality or need for invasive mechanical ventilation). Treatment with RAS inhibitor (both outpatient treatment and during hospitalization) had neither effect on mortality nor need for invasive ventilation. There were no differences in time-to-event analysis between groups. CONCLUSIONS: RAS inhibitor treatment prior to admission in patients with COVID-19 respiratory infection was associated with lower risk of the primary composite endpoint and did not show neither impact on mortality nor need for invasive mechanical ventilation, even if these drugs were prescribed during hospitalization.

Angiotensin converting enzyme inhibitors and angiotensin receptor blocker: do they increase the risk of COVID-19? / Inhibidores de la enzima convertidora de angiotensina y bloqueadores de los receptores de angiotensina II: ¿aumentan el riesgo de padecer COVID-19?

Resumen Un nuevo coronavirus, llamado coronavirus 2 del síndrome respiratorio agudo severo (SARS-CoV-2), se descubrió en diciembre de 2019 en Wuhan, China; el virus se intensificó rápidamente y el 11 de marzo de 2020 la Organización Mundial de la Salud lo declaró pandemia. Los datos emergentes sugieren que los pacientes mayores con COVID-19 asociado a otras afecciones comórbidas, como diabetes, hipertensión, y enfermedades cardíacas y pulmonares, son, en particular, más susceptibles, en comparación con las poblaciones generales y tienen mayor mortalidad. Aún no está claro si esta mayor asociación de hipertensión arterial con COVID-19 y el mayor riesgo de mortalidad están directamente relacionados con la hipertensión arterial u otras comorbilidades asociadas, o con el tratamiento antihipertensivo. Si bien el mecanismo patogénico subyacente que une la hipertensión y la gravedad de la infección por COVID-19 aún no se ha dilucidado, se ha planteado la hipótesis de que la activación excesiva del sistema renina-angiotensina (RAS) podría contribuir a la progresión de la lesión pulmonar relacionada con COVID-19. La preocupación sobre si los bloqueadores del receptor de angiotensina II (BRA) y los inhibidores de la enzima convertidora de angiotensina (IECA) pueden tener efectos nocivos sobre la morbilidad y la mortalidad de los pacientes con COVID-19 se basa en la especulación de que estos medicamentos aumentarían la regulación de la enzima convertidora de angiotensina II (ACE2), un receptor para el SARS-CoV-2, que aumentaría la carga viral y la lesión pulmonar. Los estudios recientes concuerdan con las recomendaciones de las sociedades científicas que plantean evitar la suspensión o cambio de medicación antihipertensiva, pues no hay evidencia que muestre que estos puedan ser tomados como factores de riesgo para gravedad o mortalidad por COVID-19.

Abstract A new coronavirus, called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was discovered in December 2019 in Wuhan, China; the virus escalated rapidly and on March 11, 2020, the World Health Organization declared it a pandemic. Emerging data suggests that older patients with COVID-19 associated with other comorbid conditions such as diabetes, hypertension, heart and lung diseases are particularly more susceptible, compared to general populations, and have higher mortality. It is not yet clear whether this increased association of high blood pressure with COVID-19 and the increased risk of mortality are directly related to high blood pressure or other associated comorbidities, or to antihypertensive treatment. Although the underlying pathogenic mechanism linking hypertension and severity of COVID-19 infection remains to be elucidated, it has been hypothesized that excessive activation of the renin-angiotensin system (RAS) could contribute to the progression of COVID-19 related lung injury. Concern about whether angiotensin II receptor blockers (ARBs) and angiotensin converting enzyme (ACE) inhibitors may have deleterious effects on morbidity and mortality in patients with COVID-19 is based on speculation that these drugs would increase the regulation of angiotensin II converting enzyme (ACE2), a receptor for SARS-CoV-2, which would increase viral load and lung damage. Recent studies are consistent with the recommendations of scientific societies that propose avoiding the suspension or change of antihypertensive medication, as there is no evidence that shows that these can be taken as risk factors for severity or mortality from COVID-19.