Influence of angiotensin receptor and converting enzyme blockers therapy in the respiratory outcome of COVID-19 hospitalized patients.

OBJECTIVES: COVID-19, caused by SARS-CoV-2, has spread around the world since 2019. In severe cases, COVID-19 can lead to hospitalization and death. Systemic arterial hypertension and other comorbidities are associated with serious COVID-19 infection. Literature is unclear whether antihypertensive therapy with angiotensin receptor blockers (ARBs) and angiotensin converting enzyme (ACE) inhibitors affect COVID-19 outcomes. We aim to assess whether ACEI/ARB therapy is a risk factor for worse respiratory outcomes related to COVID-19 in hospitalized patients. METHODS: Retrospective study enrolling admitted COVID-19-diagnosed patients by RT-PCR at the Hospital Geral de Fortaleza, Brazil, during 2021. Patient medical records, sociodemographic, and clinical data were analyzed. Chest CT images were analyzed using CAD4COVID-CT/Thirona™ software. RESULTS: A total of 294 patients took part in the study. A cut-off point of 66% of pulmonary involvement was found by ROC curve, with patients having higher risk of death and intubation and lower 60-day survival. Advanced age (RR 1.025, P=0.001) and intubation (RR 16.747, P<0.001) were significantly associated with a higher risk of death. Advanced age (RR 1.023, P=0.001) and the use of noninvasive ventilation (RR 1.548, P=0.037) were associated with a higher risk of intubation. Lung involvement (>66%) increased the risk of death by almost 2.5-fold (RR 2.439, P<0.001) and by more than 2.3-fold the risk of intubation (RR 2.317, P<0.001). CONCLUSIONS: Altogether, our findings suggest that ACEI or ARB therapy does not affect the risk of death and disease course during hospitalization.

Endothelial and vascular smooth muscle dysfunction in hypertension.

The development of essential hypertension involves several factors. Vascular dysfunction, characterized by endothelial dysfunction, low-grade inflammation and structural remodeling, plays an important role in the initiation and maintenance of essential hypertension. Although the mechanistic pathways by which essential hypertension develops are poorly understood, several pharmacological classes available on the clinical settings improve blood pressure by interfering in the cardiac output and/or vascular function. This review is divided in two major sections. The first section depicts the major molecular pathways as renin angiotensin aldosterone system (RAAS), endothelin, nitric oxide signalling pathway and oxidative stress in the development of vascular dysfunction. The second section describes the role of some pharmacological classes such as i) RAAS inhibitors, ii) dual angiotensin receptor-neprilysin inhibitors, iii) endothelin-1 receptor antagonists, iv) soluble guanylate cyclase modulators, v) phosphodiesterase type 5 inhibitors and vi) sodium-glucose cotransporter 2 inhibitors in the context of hypertension. Some classes are already approved in the treatment of hypertension, but others are not yet approved. However, due to their potential benefits these classes were included.

Severity of systemic lupus erythematosus with diffuse proliferative glomerulonephritis and the ineffectiveness of standard pulse intravenous cyclophosphamide therapy in Jamaican patients.

The majority of patients seen at the renal clinic of the University Hospital of the West Indies (UHWI) are of African descent. The case notes of patients with systemic lupus erythematosus (SLE) with class 4 nephritis and who were given standard pulse intravenous cyclophosphamide therapy during the period 1990-2000 were retrospectively reviewed. Primary outcomes were doubling of serum creatinine and development of end stage renal disease (ESRD). Secondary outcomes were return of proteinuria to normal and renal remission. A total of 117 patients had a renal biopsy for SLE nephritis at the UHWI between 1990 and 2000. Of the patients, 34 (29%) had diffuse proliferative glomerulonephritis (WHO class 4), of which 29 were reviewed. Twenty-two patients of 24 in whom it was measured (92%) had significant proteinuria at presentation. The 24-hour proteinuria was measured at final review in 16 patients and in 10 patients it went into complete remission. At the beginning of therapy, 24 patients (83%) had renal impairment. Of the 18 who had final creatinine values, the renal function returned to normal in eight patients (44%) and an additional six patients showed a significant improvement in renal function at final review. Six patients developed end stage renal disease (ESRD). The risk (95% confidence interval) of developing ESRD at one year was 16.2% (CI, 6.4-37.6) and at two years was 23.2% (CI, 10.0-48.5). There were three deaths, two from sepsis and one from heart failure. The one-year mortality (95% CI) was 8% (CI, 2.0-28.5), the two-year mortality was 15.6% (CI, 4.9-43.5) and the five-year mortality was also 15.6% (CI, 4.9-43.5). Intravenous pulse cyclophosphamide for Jamaican patients with SLE and diffuse proliferative glomerulonephritis is an ineffective form of treatment.

Papel dos antagonistas dos receptores da angiotensina II na insuficiência cardíaca congestiva / Role of angiotensin II antagonists receptors in congestive heart failure

O bloqueio da açäo vasoconstritora periférica da angiotensina II reduzindo a pós-carga, a diminuiçäo de seu estímulo proliferativo impedindo ou atenuando a hipertrofia e/ou a remodelaçäo miocárdica e vascular constituem claros benefícios obtidos pela modulaçäo do sistema renina-angiotensina. A proteçäo contra os efeitos pró-aterogênicos da angiotensina II, diminuindo direta ou indiretamente a incidência de doença coronária e infarto do miocárdio, constitui outro importante benefício a ser considerado. O sistema renina-angiotensina pode ser interrompido em graus variáveis pelos betabloqueadores que reduzem a secreçäo renal de renina, pelos inibidores da enzima de conversäo que limitam a conversäo da angiotensina I em angiotensina II e pelos antagonistas dos receptorees AT-I, que atuam no elo terminal no sistema. Baseando-se nesses fundamentos de fisiopatologia e nas evidências favoráveis de grandes estudos que utilizaram, com sucesso, inibidores da enzima conversora no tratamento da insuficiência cardíaca congestiva, passou-se a analisar o emprego de antagonistas de receptores da angiotensina II em tal situaçäo. Os primeiros resultados demonstram melhora da tolerância ao exercício com o uso dos antagonistas da angiotensina e, no estudo Resolved, constatou-se efeito sinérgico com a adiçäo de inibidor da enzima conversora, obtendo-se valores mais altos da fraçäo de ejeçäo. A conclusäo do primeiro grande estudo (ELITE II) comparando-os no tratamento da insuficiência cardíaca congestiva revelou ausência de diferença significativa entre essas duas classes terapêuticas. Nos próximos anos, os resultados de outros grandes estudos em andamento nos permitiräo escolher, para cada paciente, a droga que seja mais bem indicada (ou, eventualmente, sua associaçäo), considerando a tolerabilidade, o custo/benefício e a comodidade posológica.

Antagonistas de los receptores de angiotensina II / Angiotensin II receptors antagonists

Se propuso revisar los nuevos conocimientos sobre los receptores de la angiotensina II y las implicaciones clinicas y terapéuticas derivadas de su bloqueo farmacológico. Se destacó la reconocida importancia del sistema renina-angiotensina en la regulación cardiovascular y renal y se explicó que sus efectos están medidos por la acción de la AII sobre sus receptores (tipo I y tipo 2). Se concluyó que los recientes avances en el control farmacológico de ese sistema, especialmente por la aparición de nuevos antagonistas de los receptores de la AII activos por vía oral, como el losartán, pueden ser de extraordinaria eficacia en el tratamiento de la hipertensión arterial, insuficiencia cardíacas y en evitar la progresión de la insuficiencia renal crónica(AU)