scholarly journals The Effect of Chronic and Inhospital Exposure to Renin-Angiotensin System Inhibitors on the Outcome and Inflammatory State of Coronavirus Disease 2019 Adult Inpatients

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Pedro Gaspar ◽  
Inês Parreira ◽  
Pedro Antunes Meireles ◽  
Filipe Bessa ◽  
Virgílio Dias Silva ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Invasive Mechanical Ventilation ◽  
Multivariable Analysis ◽  
Renin Angiotensin System ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Icu Admission ◽  
Risk Of Death ◽  
Asymptomatic Patients ◽  
The Impact

Background. Controversies exist about the effect of renin-angiotensin system inhibitors (RASi) on coronavirus disease 2019 (COVID-19) outcome. The inhospital use of RASi and its effect on inflammatory sate are still poorly studied during the COVID-19 pandemic. Objectives. We aimed to compare the impact of previous and inhospital RASi exposure on the outcome and inflammatory response of COVID-19 patients. Methods. Single-centre, ambispective analysis of hospitalized adult COVID-19 patients at Hospital de Santa Maria, Lisbon, between March and August 2020 was performed. We excluded asymptomatic patients and those admitted due to another disease. The primary outcome was inhospital all-cause mortality. Illness severity was assessed based on the development of acute respiratory distress syndrome/acute lung injury (ARDS/ALI), intensive care unit (ICU) admission, and need for invasive mechanical ventilation (IMV). We used C-reactive protein (CRP), ferritin, and interleukin 6 (IL-6) as surrogate markers of the inflammatory response. Results. From a total of 432 patients, 279 were selected, among whom 133 (47.7%) were receiving a RASi. Chronic treatment with RASi was not associated with the risk of death (OR 1.24, 95% CI 0.66–2.31, p = 0.500 ), ARDS/ALI development (OR 1.12, 95% CI 0.67–1.86, p = 0.676 ), ICU admission (OR 1.11, 95% CI 0.67–1.84, p = 0.686), and IMV need (OR 1.03, 95% CI 0.58–1.84, p = 0.917 ) in a univariable and multivariable analysis. Inhospital RASi withdrawing was associated with the risk of death (OR 4.38, 95% CI 1.11–17.21, p = 0.035 ) and ARDS/ALI development (OR 4.33, 95% CI 1.49–12.6, p = 0.007 ), the latter remaining significant after adjustment. Previous exposure to RASi was associated with lower CRP levels at admission ( p = 0.018 ). IL-6 levels were significantly higher in those patients whose RASi were stopped ( p = 0.024 ). Conclusion. Previous and inhospital exposure to RASi was not associated with mortality nor severity of COVID-19. This study supports current guidance on RASi management during the COVID-19 pandemic.

scholarly journals Outcomes of COVID-19 Hospitalized Patients Previously Treated with Renin-Angiotensin System Inhibitors

2020 ◽  
Vol 9 (11) ◽  
pp. 3472 ◽  
Author(s):  
Elena-Mihaela Cordeanu ◽  
Lucas Jambert ◽  
Francois Severac ◽  
Hélène Lambach ◽  
Jonathan Tousch ◽  
...  
Keyword(s):  
Renin Angiotensin System ◽  
Severe Pneumonia ◽  
University Hospital ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Renin Angiotensin ◽  
Previously Treated ◽  
The Impact ◽  
Harmful Effects ◽  
Observation Period

(1) Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) penetrates respiratory epithelium through angiotensin-converting enzyme-2 binding, raising concerns about the potentially harmful effects of renin–angiotensin system inhibitors (RASi) on Human Coronavirus Disease 2019 (COVID-19) evolution. This study aimed to provide insight into the impact of RASi on SARS-CoV-2 outcomes in patients hospitalized for COVID-19. (2) Methods: This was a retrospective analysis of hospitalized adult patients with SARS-CoV-2 infection admitted to a university hospital in France. The observation period ended at hospital discharge. (3) Results: During the study period, 943 COVID-19 patients were admitted to our institution, of whom 772 were included in this analysis. Among them, 431 (55.8%) had previously known hypertension. The median age was 68 (56–79) years. Overall, 220 (28.5%) patients were placed under mechanical ventilation and 173 (22.4%) died. According to previous exposure to RASi, we defined two groups, namely, “RASi” (n = 282) and “RASi-free” (n = 490). Severe pneumonia (defined as leading to death and/or requiring intubation, high-flow nasal oxygen, noninvasive ventilation, and/or oxygen flow at a rate of ≥5 L/min) and death occurred more frequently in RASi-treated patients (64% versus 53% and 29% versus 19%, respectively). However, in a propensity score-matched cohort derived from the overall population, neither death (hazard ratio (HR) 0.93 (95% confidence interval (CI) 0.57–1.50), p = 0.76) nor severe pneumonia (HR 1.03 (95%CI 0.73–1.44), p = 0.85) were associated with RASi therapy. (4) Conclusion: Our study showed no correlation between previous RASi treatment and death or severe COVID-19 pneumonia after adjustment for confounders.

scholarly journals 910. A Comprehensive, One Year, Hospital-Wide Snapshot of All Serious Infectious Complications in People Who Inject Drugs

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S489-S490
Author(s):  
John T Henderson ◽  
Evelyn Villacorta Cari ◽  
Nicole Leedy ◽  
Alice Thornton ◽  
Donna R Burgess ◽  
...  
Keyword(s):  
Multivariable Analysis ◽  
Vertebral Osteomyelitis ◽  
The United States ◽  
Infectious Complications ◽  
Data Set ◽  
Cumulative Impact ◽  
Mortality And Morbidity ◽  
Icu Admission ◽  
Risk Of Death ◽  
The Impact

Abstract Background There has been a dramatic rise in IV drug use (IVDU) and its associated mortality and morbidity, however, the scope of this effect has not been described. Kentucky is at the epicenter of this epidemic and is an ideal place to better understand the health complications of IVDU in order to improve outcomes. Methods All adult in-patient admissions to University of Kentucky hospitals in 2018 with an Infectious Diseases (ID) consult and an ICD 9/10 code associated with IVDU underwent thorough retrospective chart review. Demographic, descriptive, and outcome data were collected and analyzed by standard statistical analysis. Results 390 patients (467 visits) met study criteria. The top illicit substances used were methamphetamine (37.2%), heroin (38.2%), and cocaine (10.3%). While only 4.1% of tested patients were HIV+, 74.2% were HCV antibody positive. Endocarditis (41.1%), vertebral osteomyelitis (20.8%), bacteremia without endocarditis (14.1%), abscess (12.4%), and septic arthritis (10.4%) were the most common infectious complications. The in-patient death rate was 3.0%, and 32.2% of patients were readmitted within the study period. The average length of stay was 26 days. In multivariable analysis, infectious endocarditis was associated with a statistically significant increase in risk of death, ICU admission, and hospital readmission. Although not statistically significant, trends toward mortality and ICU admission were identified for patients with prior endocarditis and methadone was correlated with decreased risk of readmission and ICU stay. FIGURE 1: Reported Substances Used FIGURE 2: Comorbidities FIGURE 3: Types of Severe Infectious Complications Conclusion We report on a novel, comprehensive perspective on the serious infectious complications of IVDU in an attempt to measure its cumulative impact in an unbiased way. This preliminary analysis of a much larger dataset (2008-2019) reveals some sobering statistics about the impact of IVDU in the United States. While it confirms the well accepted mortality and morbidity associated with infective endocarditis and bacteremia, there is a significant unrecognized impact of other infectious etiologies. Additional analysis of this data set will be aimed at identifying key predictive factors in poor outcomes in hopes of mitigating them. Disclosures All Authors: No reported disclosures

Gene variants of the renin–angiotensin system and hypertension: from a trough of disillusionment to a welcome phase of enlightenment?

2010 ◽  
Vol 118 (8) ◽  
pp. 487-506 ◽  
Author(s):  
Gavin R. Norton ◽  
Richard Brooksbank ◽  
Angela J. Woodiwiss
Keyword(s):  
Association Studies ◽  
Large Population ◽  
Renin Angiotensin System ◽  
Human Populations ◽  
Incomplete Penetrance ◽  
Gene Variants ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Ras Genes ◽  
The Impact

There is substantial evidence to suggest that BP (blood pressure) is an inherited trait. The introduction of gene technologies in the late 1980s generated a sharp phase of over-inflated prospects for polygenic traits such as hypertension. Not unexpectedly, the identification of the responsible loci in human populations has nevertheless proved to be a considerable challenge. Common variants of the RAS (renin–angiotensin system) genes, including of ACE (angiotensin-converting enzyme) and AGT (angiotensinogen) were some of the first shown to be associated with BP. Presently, ACE and AGT are the only gene variants with functional relevance, where linkage studies showing relationships with hypertension have been reproduced in some studies and where large population-based and prospective studies have demonstrated these genes to be predictors of hypertension or BP. Nevertheless, a lack of reproducibility in other linkage and association studies has generated scepticism that only a concerted effort to attempt to explain will rectify. Without these explanations, it is unlikely that this knowledge will translate into the clinical arena. In the present review, we show that many of the previous concerns in the field have been addressed, but we also argue that a considerable amount of careful thought is still required to achieve enlightenment with respect to the role of RAS genes in hypertension. We discuss whether the previously identified problems of poor study design have been completely addressed with regards to the impact of ACE and AGT genes on BP. In the context of RAS genes, we also question whether the significance of ‘incomplete penetrance’ through associated environmental, phenotypic or physiological effects has been duly accounted for; whether appropriate consideration has been given to epistatic interactions between genes; and whether future RAS gene studies should consider variation across the gene by evaluating ‘haplotypes’.

scholarly journals Association of Proteinuria and Hematuria with Acute Kidney Injury and Mortality in Hospitalized Patients with COVID-19

2020 ◽  
Vol 45 (6) ◽  
pp. 1018-1032
Author(s):  
Imran Chaudhri ◽  
Richard Moffitt ◽  
Erin Taub ◽  
Raji R. Annadi ◽  
Minh Hoai ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Invasive Mechanical Ventilation ◽  
Multivariable Analysis ◽  
Kidney Injury ◽  
Hospitalized Patients ◽  
Hospital Death ◽  
Study Cohort ◽  
Icu Admission ◽  
Risk Of Death ◽  
Increased Risk

<b><i>Introduction:</i></b> Acute kidney injury (AKI) is strongly associated with poor outcomes in hospitalized patients with coronavirus disease 2019 (COVID-19), but data on the association of proteinuria and hematuria are limited to non-US populations. In addition, admission and in-hospital measures for kidney abnormalities have not been studied separately. <b><i>Methods:</i></b> This retrospective cohort study aimed to analyze these associations in 321 patients sequentially admitted between March 7, 2020 and April 1, 2020 at Stony Brook University Medical Center, New York. We investigated the association of proteinuria, hematuria, and AKI with outcomes of inflammation, intensive care unit (ICU) admission, invasive mechanical ventilation (IMV), and in-hospital death. We used ANOVA, <i>t</i> test, χ<sup>2</sup> test, and Fisher’s exact test for bivariate analyses and logistic regression for multivariable analysis. <b><i>Results:</i></b> Three hundred patients met the inclusion criteria for the study cohort. Multivariable analysis demonstrated that admission proteinuria was significantly associated with risk of in-hospital AKI (OR 4.71, 95% CI 1.28–17.38), while admission hematuria was associated with ICU admission (OR 4.56, 95% CI 1.12–18.64), IMV (OR 8.79, 95% CI 2.08–37.00), and death (OR 18.03, 95% CI 2.84–114.57). During hospitalization, de novo proteinuria was significantly associated with increased risk of death (OR 8.94, 95% CI 1.19–114.4, <i>p</i> = 0.04). In-hospital AKI increased (OR 27.14, 95% CI 4.44–240.17) while recovery from in-hospital AKI decreased the risk of death (OR 0.001, 95% CI 0.001–0.06). <b><i>Conclusion:</i></b> Proteinuria and hematuria both at the time of admission and during hospitalization are associated with adverse clinical outcomes in hospitalized patients with COVID-19.

P1661The myocardial tissue Renin-Angiotensin-System (RAS) of the failing heart

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
N Pavo ◽  
H Arfsten ◽  
R Wurm ◽  
S Prausmueller ◽  
G Spinka ◽  
...  
Keyword(s):  
Disease Progression ◽  
Renin Angiotensin System ◽  
Inhibitor Therapy ◽  
Myocardial Tissue ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Failing Heart ◽  
End Stage ◽  
The Impact ◽  
Nep Inhibition

Abstract Background Prognosis of patients with HFrEF remains poor despite recent advances in pharmacologic therapy as the introduction of the angiotensin-receptor neprilysin-inhibitor (ARNI). The Renin-Angiotensin-System (RAS) is dysregulated in HF with elevated AngII levels as a central driver of disease progression. The myocardium is capable of synthesizing all RAS components resulting in tissue specific angiotensin levels. Neprilysin (NEP) catalyzes the generation of Ang1–7 which counteracts the deleterious effects of AngII. Myocardial tissue angiotensins of the failing heart and the role of long-lasting RAS-inhibitor therapy and particularly NEP inhibition on tissue RAS have not been investigated yet. Methods Concentrations of AngI, AngII, Ang1–7, AngIII, Ang1–5 and AngIV (RAS-fingerprints) were investigated in myocardial samples of end-stage HFrEF patients undergoing heart transplantation with a mass-spectrometry based method. Patients were stratified according to background therapy with RAS-inhibitors and variables were compared by a non-parametrical test. Results A total of 30 patients were included (n=6 without RAS-blockade, n=16 with ACE-I, n=6 with ARB and n=2 with ARNI). Median age was 55 (IQR 45–63) years and 87% of patients were male. 40% of patients had an ischemic etiology of HF, median NT-proBNP levels were 3498pg/ml (IQR 1761–8400). Tissue RAS patterns were visually similar between all groups (Figure 1). Myocardial AngI, Ang1–7, Ang1–5 and AngIV levels were below the detection limit for all samples. Median tissue AngII and AngIII concentrations across all samples were 83.1pg/ml (IQR 29.3–196.6) and 26.4pg/ml (IQR 5.0–64.5). Despite different background RAS-inhibitor therapy, AngII and AngIII levels were comparable between all groups [median (IQR) in pg/ml – AngII: 51.5 (41.5–123.8) vs. 72.4 (28.5–177.6) vs. 176.1 (22.4–286.8) vs. 266.0 (108.2–423.8); p=ns and 26.4 (5.0–89.2) vs. 23.2 (5.0–59.3) vs. 39.4 (5.0–94.3) vs. 105.9 (46.5–165.3); p=ns for no therapy, ACE-I, ARB and ARNI respectively]. Figure 1. RAS-fingerprints of the failing heart according to RAS-inhibiton. Numbers in brackets indicate the specific angiotensin peptides. Side of spheres and numbers beside represent absolute concentrations of angiotensins (pg/ml, median value). Conclusions Although in the plasma of HFrEF patients only AngI and AngII are detectable at substantial concentrations, the predominant angiotensins of the failing heart are AngII and AngIII. AngII levels are high in the failing heart supporting the hypothesis that excess AngII is involved in disease progression. AngIII similarly increases cardiac sympathetic activity assumedly potentiating further deteoriation. The modality of long established RAS-inhibitor therapy in end-stage HF, particularly the inhibition of NEP, seems to have no (more) influence on myocardial tissue RAS regulation. The impact of NEP inhibition by ARNI on tissue RAS enzymes and mechanism of action need to be further investigated.

scholarly journals Modeling the Molecular Impact of SARS-CoV-2 Infection on the Renin-Angiotensin System

Viruses ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 1367
Author(s):  
Fabrizio Pucci ◽  
Philippe Bogaerts ◽  
Marianne Rooman
Keyword(s):  
Renin Angiotensin System ◽  
Therapeutic Strategies ◽  
Spike Protein ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Pathogenic Mechanisms ◽  
Renin Angiotensin ◽  
Factors Associated ◽  
Ras Blockers ◽  
The Impact

SARS-CoV-2 infection is mediated by the binding of its spike protein to the angiotensin-converting enzyme 2 (ACE2), which plays a pivotal role in the renin-angiotensin system (RAS). The study of RAS dysregulation due to SARS-CoV-2 infection is fundamentally important for a better understanding of the pathogenic mechanisms and risk factors associated with COVID-19 coronavirus disease and to design effective therapeutic strategies. In this context, we developed a mathematical model of RAS based on data regarding protein and peptide concentrations; the model was tested on clinical data from healthy normotensive and hypertensive individuals. We used our model to analyze the impact of SARS-CoV-2 infection on RAS, which we modeled through a downregulation of ACE2 as a function of viral load. We also used it to predict the effect of RAS-targeting drugs, such as RAS-blockers, human recombinant ACE2, and angiotensin 1–7 peptide, on COVID-19 patients; the model predicted an improvement of the clinical outcome for some drugs and a worsening for others. Our model and its predictions constitute a valuable framework for in silico testing of hypotheses about the COVID-19 pathogenic mechanisms and the effect of drugs aiming to restore RAS functionality.

scholarly journals Kallikrein–kinin system as the dominant mechanism to counteract hyperactive renin–angiotensin system

2017 ◽  
Vol 95 (10) ◽  
pp. 1117-1124 ◽  
Author(s):  
Domenico Regoli ◽  
Fernand Gobeil
Keyword(s):  
Renin Angiotensin System ◽  
Biologically Active ◽  
Ang Ii ◽  
Kinin System ◽  
Angiotensin System ◽  
Dominant Mechanism ◽  
Renin Angiotensin ◽  
First Choice ◽  
Kallikrein Kinin System ◽  
The Impact

The renin–angiotensin system (RAS) generates, maintains, and makes worse hypertension and cardiovascular diseases (CVDs) through its biologically active component angiotensin II (Ang II), that causes vasoconstriction, sodium retention, and structural alterations of the heart and the arteries. A few endogenous vasodilators, kinins, natriuretic peptides, and possibly angiotensin (1-7), exert opposite actions and may provide useful therapeutic agents. As endothelial autacoids, the kinins are potent vasodilators, active natriuretics, and protectors of the endothelium. Indeed, the kallikrein–kinin system (KKS) is considered the dominant mechanism for counteracting the detrimental effects of the hyperactive RAS. The 2 systems, RAS and KKS, are controlled by the angiotensin-converting enzyme (ACE) that generates Ang II and inactivates the kinins. Inhibitors of ACE can reduce the impact of Ang II and potentiate the kinins, thus contributing to restore the cardiovascular homeostasis. In the last 20 years, ACE-inhibitors (ACE-Is) have become the drugs of first choice for the treatments of the major CVDs. ACE-Is not only reduce blood pressure, as sartans also do, but by protecting and potentiating the kinins, they can reduce morbidity and mortality and improve the quality of life for patients with CVDs. This paper provides a brief review of the literature on this topic.

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