DrugBank ID: db04630
DrugCentral: aldosterone
Synonymous :(+)-aldosterone | (11β)-11,21-dihydroxy-3,20-dioxopregn-4-en-18-al | 11beta,21-dihydroxy-3,20-dioxo-4-pregnen-18-al | 11beta,21-dihydroxy-3,20-dioxopregn-4-en-18-al | aldosterona | aldosterone | aldosteronum

Drug Sentece Context

Table 1. Analysis of context sentence of aldosterone gene in 25 abstracts.

pmid sentence
32228252 ACE2, however, is a key enzymatic component of the renin-angiotensin-aldosterone system (RAAS); ACE2 degrades ANG II, a peptide with multiple actions that promote CVD, and generates Ang-(1-7), which antagonizes the effects of ANG II.
32301766 Additionally, renin-angiotensin aldosterone system inhibitors reduce adverse atherosclerotic cardiovascular disease, heart failure and chronic kidney disease outcomes, but may increase ACE2 levels. […] We review current knowledge of the role of ACE2 in cardiovascular physiology and SARS-CoV-2 virology as well as clinical data to inform the management of patients with or at risk for COVID-19 who require renin-angiotensin-aldosterone system inhibitor therapy.
32314329 ACE2 counteracts ACE and angiotensin II in the renin-angiotensin-aldosterone system (RAAS) and has critical functions in the lung and cardiovascular system.
32324352 Inhibitors of the renin-angiotensin aldosterone system should be continued when there is a solid indication, and stopped in case of hemodynamic problems.
32341103 The renin-angiotensin-aldosterone system (RAAS) is crucial to the homeostasis of both the cardiovascular and respiratory systems. […] Importantly, SARS-CoV-2 utilises and interrupts this pathway directly, which could be described as the renin-angiotensin-aldosterone-SARS-CoV-2-axis (RAAS-SCoV-axis).
32348783 Early clinical evidence suggests that severe cases of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are frequently characterized by hyperinflammation, imbalance of renin-angiotensin-aldosterone system, and a particular form of vasculopathy, thrombotic microangiopathy, and intravascular coagulopathy.
32352535 Moreover, renin-angiotensin-aldosterone system (RAAS) inhibitors might be beneficial in COVID-19.
32354022 ACE2 plays an essential role in the renin-angiotensin-aldosterone system (RAAS), which regulates blood pressure and fluid balance.
32354800 Specific cardiovascular considerations are also necessary in supportive treatment with anticoagulation, the continued use of renin-angiotensin-aldosterone system inhibitors, arrhythmia monitoring, immunosuppression or modulation, and mechanical circulatory support.
32356628 There is concern about the potential of an increased risk related to medications that act on the renin-angiotensin-aldosterone system in patients exposed to coronavirus disease 2019 (Covid-19), because the viral receptor is angiotensin-converting enzyme 2 (ACE2).
32360703 Physiologically, ACE2 degrades angiotensin II, the master regulator of the renin-angiotensin-aldosterone system (RAAS), thereby converting it into vasodilatory molecules, which have well-documented cardio-protective effects.
32366740 A concern was raised regarding the safety of ibuprofen use because of its role in increasing ACE2 levels within the Renin-Angiotensin-Aldosterone system.
32367746 Coronavirus binding to angiotensin-converting enzyme 2, a crucial component of the renin-angiotensin-aldosterone system, underlies much of this concern. […] We briefly summarize the renin-angiotensin-aldosterone system and comprehensively review the literature pertaining to the angiotensin-converting enzyme 2/angiotensin-(1-7) pathway in children and the clinical evidence for how angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers affect this important pathway.
32376099 In this article, we review the evidence on the relationship between the renin-angiotensin-aldosterone system and COVID-19 infection.
32383624 This might be due to the fact that ACE2 is the receptor for the virus to enter human cells, but, on the contrary, that ACE2 expression is downregulated following SARS-1 infection, resulting in disproportionate activation of renin-angiotensin-aldosterone system and exacerbated pneumonia progression.
32387238 SARS-CoV-2 has a major impact on the Renin Angiotensin Aldosterone System (RAAS), through its binding to the membrane cellular glycoprotein, Angiotensin Converting Enzyme-2 (ACE-2), then infecting cells for replication.
32388331 Compromised innate immunity, pro-inflammatory cytokine milieu, reduced expression of ACE2 and use of renin-angiotensin-aldosterone system antagonists in people with diabetes mellitus contribute to poor prognosis in COVID-19.
32388565 Recent reports suggest an association with use of renin-angiotensin-aldosterone system (RAAS) inhibitors.
32391169 During infection and its complication such as sepsis, hypotension could be exacerbated by antihypertensive drugs because homeostasis mechanisms such as sodium balance, renin angiotensin aldosterone system and/or sympathetic nervous system can be mitigated by antihypertensive drug therapy. […] Despite the theoretical concerns of increased ACE2 expression by Renin-Angiotensin-Aldosterone system (RAS) blockade, there is no evidence that RAS inhibitors are harmful during COVID-19 infection and have in fact been shown to be beneficial in animal studies.
32394850 The review addressed the relationship of coronavirus disease 2019 (COVID-19) with functioning of the renin-angiotensin-aldosterone axis and the causes for unfavorable prognosis depending on patients’ age and comorbidities.
32401442 ACE2 is not only an enzyme that counters the effects of the renin-angiotensin-aldosterone system (RAAS) but is also the entry receptor for SARS-CoV-2, the virus of the Covid-19 pandemic.
32405229 Some investigations speculated about the association between the renin-angiotensin-aldosterone system (RAAS) and susceptibility to COVID-19, as well as the relationship between RAAS inhibitors and the adverse outcome in these patients.
32412156 A key role may be that of the renin-angiotensin-aldosterone system.
32412303 Like other coronaviruses, SARS-CoV-2 recognizes the human Angiotensin Converting Enzyme 2 (hACE2) as a cellular receptor that allows it to infect different host cells, and likely disrupts the renin-angiotensin-aldosterone system (RAAS) homeostasis.
32413342 There are currently no recommendations in favour of discontinuing antihypertensive medications that interact with the renin-angiotensin-aldosterone system.
32414646 This molecule is a peptidase expressed at the surface of lung epithelial cells and other tissues, that regulates the renin-angiotensin-aldosterone system.
32416785 Concerns have been raised about the possibility that inhibitors of the renin-angiotensin-aldosterone system (RAAS) could predispose individuals to severe COVID-19; however, epidemiological evidence is lacking.
32418199 In human physiology, ACE2 is a pivotal counter-regulatory enzyme to ACE by the breakdown of angiotensin II, the central player in the renin-angiotensin-aldosterone system (RAAS) and the main substrate of ACE2.
32418532 SARS-CoV-2 / COVID-19 and the ‘Renin-Angiotensin’ System The ubiquitous ‘Renin-Angiotensin’ system (RAS), also referred to as ‘Renin-Angiotensin-Aldosterone’ system, plays a crucial physiological role in humans as being a key regulator of renal, cardiovascular and innate immune functions [1, 2].
32420884 Despite the rapid evolution of data on this pandemic, this review aims to highlight the cardiovascular considerations related to COVID-19 whether as comorbidities including concerns and uncertainty regarding the effect of renin-angiotensin-aldosterone system (RAAS) inhibitors on angiotensin conversion enzyme 2 or related to acute cardiovascular complications.
32421367 The main host receptor of the SARS-CoV-2 is angiotensin converting enzyme 2 (ACE2), a major component of the renin-angiotensin-aldosterone system (RAAS).
32432519 We discuss the possible excess risk for COVID-19 infection in the context of the common conditions among shiftworkers, including nurses, doctors, and first responders, among others of high exposure to the contagion, of sleep imbalance and circadian disruption.Abbreviations: ACE2: Angiotensin-converting enzyme 2; APC: Antigen-presenting cells; CCL: Chemokine (C-C motif) ligand; CD+: Adhesion molecule expression; COVID-19: 2019 coronavirus disease; DCs: Dendritic cells; GH: Growth hormone; HPA: Hypothalamic-pituitary-adrenal; HSF: Heat shock factor; HSP70: Heat shock protein 70; HSP90: Heat shock protein 90; IL: Interleukin; INFγ: Interferon-gamma; LT/LB: T/B lymphocytes; MHC: Major histocompatibility complex; NK: Natural killer; RAAS: renin-angiotensin-aldosterone system; SARS: Severe acute respiratory syndrome; SCN: Suprachiasmatic nucleus;SD: Sleep deprivation; SNS: Sympathetic nervous system; Th1/Th2: T helper lymphocytes 1/2; TLR2/TLR4: Toll-like receptor 2/4; TNF-α: Tumor necrosis factor alpha; VEGF: Vascular endothelial growth factor.
32435607 As a crucial enzyme of renin-angiotensin-aldosterone system (RAAS), ACE2 not only mediates the virus entry but also affects the pathophysiological process of virus-induced acute lung injury (ALI), as well as other organs’ damage.
32442285 Renin-angiotensin-aldosterone system (RAAS) inhibitors may facilitate host cell entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or attenuate organ injury via RAAS blockade.
32446267 Kidney transplant recipients are commonly prescribed renin-angiotensin-aldosterone system (AAS) inhibitors given the prevalence of hypertension, diabetes, and cardiovascular disease. […] As the angiotensin-converting enzyme 2 (ACE2) facilitates the entry of coronaviruses into target cells, there have been hypotheses that preexisting use of Renin-Angiotensin-Aldosterone System (RAAS) inhibitors may increase the risk of developing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.
32452762 Genetic alteration of ENaC-α causes aldosterone dysregulation in patients, highlighting that the FURIN site is critical for activation of ENaC.
32458694 The continued use of angiotensin converting enzyme inhibitor (ACEIs) and angiotensin II receptor blockers (ARBs) which are part of renin-angiotensin-aldosterone system (RAAS) inhibitors in COVID-19 patients with hypertension has become controversial.
32461198 Some investigations speculated about the association between the renin-angiotensin-aldosterone system (RAAS) and susceptibility to COVID-19, as well as the relationship between RAAS inhibitors and the adverse outcome in these patients.
32470515 The coronavirus disease 2019 (COVID-19) is caused by SARS-CoV2 that interfaces with the renin-angiotensin-aldosterone system (RAAS) through angiotensin-converting enzyme 2 (ACE-2).
32472191 In univariate analysis, characteristics prior to admission significantly associated with the primary outcome were sex, BMI and previous treatment with renin-angiotensin-aldosterone system (RAAS) blockers, but not age, type of diabetes, HbA1c, diabetic complications or glucose-lowering therapies.
32496364 When the coronavirus disease 2019 (COVID-19) wreaked an unprecedented havoc of an escalating number of deaths and hospitalization in the United States, clinicians were faced with a myriad of unanswered questions, one of the them being the implication of the renin-angiotensin-aldosterone system in patients with COVID-19.
32498076 The mortality rates were similar between the renin-angiotensin-aldosterone system (RAAS) inhibitor (4/183) and non-RAAS inhibitor (19/527) cohorts (2.2% vs. 
32501190 Demographic and clinical comorbidities associated with the severity of infection suggest that possible variants known to influence the renin-angiotensin-aldosterone system pathway (particularly those that influence ACE2) may contribute to the heterogenous infection response. […] Hypertension medication modulation, may alter ACE2 and angiotensin(1-7), particularly in variants that have been shown to influence renin-angiotensin-aldosterone system function, which could be clinically useful in patients with COVID-19.
32511678 The effect of chronic use of renin-angiotensin-aldosterone system (RAAS) inhibitors on the severity of COVID-19 infection is still unclear in patients with hypertension.
32523145 The drugs that act on the renin-angiotensin-aldosterone system are in many cases the backbone for the management of these diseases, it has been known for a long time that these drugs significantly increase the expression of receptors for angiotensin conversion enzyme type 2 in the lung tissue.
32527699 Debate has been generated as to the association between antihypertensive therapy with renin-angiotensin-aldosterone system (RAAS) inhibitors and SARS-CoV-2 infection.
32544563 The virus-mediated down-regulation of ACE2 causes a burst of inflammatory cytokine release through dysregulation of the renin-angiotensin-aldosterone system (ACE/angiotensin II/AT1R axis), attenuation of Mas receptor (ACE2/MasR axis), increased activation of [des-Arg9]-bradykinin (ACE2/bradykinin B1R/DABK axis), and activation of the complement system including C5a and C5b-9 components.
32550040 On the other hand, ACE2 negatively regulates the renin-angiotensin-aldosterone system (RAAS) primarily by converting angiotensin II to angiotensin 1-7, which exerts a beneficial effect on coronavirus-induced acute lung injury.
32558211 We explore potential interactions between anti-diabetic medications and renin-angiotensin-aldosterone-system inhibitors with COVID-19.
32565254 SARS-CoV2 has been suggested to modulate the renin-angiotensin-aldosterone system (RAAS).
32567171 Obesity is usually associated with dysregulated renin-angiotensin-aldosterone (RAAS) axis.
32574273 ACE2 is part of the wider renin-angiotensin-aldosterone system (RAAS) and is upregulated via compounds, which inhibits the classical ACE, thereby plasma aldosterone and aldosterone receptor (MR) activation.
32581799 We examine the crosstalk between the renin-angiotensin-aldosterone system and mitogen activated kinase pathways that potentially links cardiovascular predisposition and/or outcome to SARS-CoV-2 infection.
32582574 In this perspective, we predominantly focus on the impact of SARS-CoV-2 infection on ACE2 and dysregulation of the protective effect of ACE2/MAS/G protein pathway vs. the deleterious effect of Renin/Angiotensin/Aldosterone. […] We discuss the potential effect of invasion of SARS-CoV-2 on the function of ACE2 and the loss of the protective effect of the ACE2/MAS pathway in alveolar epithelial cells and how this may amplify systemic deleterious effect of renin-angiotensin aldosterone system (RAS) in the host.
32589258 Use of renin-angiotensin-aldosterone system inhibitors was not associated with mortality after adjusting by baseline risk factors.
32624690 Despite angiotensin-converting enzyme 2 serving as the portal for infection, the continuation of clinically indicated renin-angiotensin-aldosterone blockers is recommended according to the present evidence.
32627330 Some investigations speculated about the association between renin-angiotensin-aldosterone system (RAAS) and susceptibility to COVID-19, as well as the relationship between RAAS inhibitors and increased mortality in these patients.
32628137 Renin-angiotensin-aldosterone-system (RAAS) inhibitors may increase the expression of angiotensin-converting enzyme 2, which is the receptor for SARSCoV-2 Spike protein.
32653530 In this brief review, we discuss the effect of ACE inhibitor-induced bradykinin on the cardiovascular system, on the renin-angiotensin-aldosterone system (RAAS) regulation in COVID-19 patients, and analyze recent clinical studies regarding patients treated with RAAS inhibitors.
32654082 Endothelial dysfunction, activation of the renin-angiotensin-aldosterone system (RAAS) with the release of procoagulant plasminogen activator inhibitor (PAI-1), and hyperimmune response with activated platelets seem to be significant contributors to thrombogenesis in COVID-19.
32654555 This study aimed to clarify the impact of hypertension on COVID-19 and investigate whether the prior use of renin-angiotensin-aldosterone system (RAAS) inhibitors affects the prognosis of COVID-19.
32654557 There have been concerns on whether alterations of ACE2 expression by renin-angiotensin-aldosterone system (RAAS) inhibitors would contribute to the infectivity and severity of coronavirus disease 2019 (COVID-19).
32658389 In the present review, we highlight possible pathways involved in the pathogenesis of COVID-19 and potential therapeutic targets, focusing on the role of the renin-angiotensin-aldosterone system.
32662949 On the basis of the link between inflammation, fibrosis, aldosterone, and extracellular matrix regulation, we aimed to investigate the effect of an early intervention with the mineralocorticoid receptor antagonist (MRA) eplerenone on cardiac remodelling in a murine model of persistent coxsackievirus B3 (CVB3)-induced myocarditis.
32691370 Angiotensin-converting enzyme 2 (ACE2) plays an important role as a member of the renin-angiotensin-aldosterone system (RAAS) in regulating the conversion of angiotensin II (Ang II) into angiotensin (1-7) (Ang [1-7]).
32700055 Additional facets include the sympathetic adrenergic system, for which adrenaline is the key effector; the hypothalamic-pituitary-adrenocortical axis; arginine vasopressin (synonymous with anti-diuretic hormone); the renin-angiotensin-aldosterone system, with angiotensin II and aldosterone the main effectors; and cholinergic anti-inflammatory and sympathetic inflammasomal pathways.
32708205 The new coronavirus SARS-CoV-2, responsible for the Covid-19 pandemic, uses the angiotensin converting enzyme type 2 (ACE2), a physiological inhibitor of the renin angiotensin aldosterone system (RAAS), as a cellular receptor to infect cells. […] Thus, we aimed to determine the levels of plasma renin and aldosterone as indicators of RAAS activation in a series of consecutively admitted patients for Covid-19 in our clinic. […] Plasma renin and aldosterone levels were measured, among the miscellaneous investigations needed for Covid-19 management, early after admission in our clinic. […] In univariate analyses, aldosterone and C-reactive protein (CRP) levels at inclusion were significantly higher in patients with severe clinical course as compared to those with mild or moderate course (p < 0.01 and p = 0.03, respectively). […] In multivariate analyses, only aldosterone and CRP levels remained positively associated with severity. […] We also observed a positive significant correlation between aldosterone and CRP levels among patients with an aldosterone level greater than 102.5 pmol/L. […] Both plasmatic aldosterone and CRP levels at inclusion are associated with the clinical course of Covid-19.
32710674 In conclusion, our data support that receiving renin-angiotensin-aldosterone system inhibitors does not predispose for suffering COVID-19 infection in ambulatory hypertensive people.
32711111 Additionally, by inducing an imbalance in the renin-angiotensin-aldosterone system (RAAS) and the loss of ACE2 would favour the progression of inflammatory and thrombotic processes in the lungs.
32712300 The use of ACEIs/ARBs (RAAS inhibitors) regulates the renin-angiotensin-aldosterone system (RAAS) and may increase ACE2 expression.
32718670 Of interest, another mechanistic approach responds to considering the inhibition of the renin-angiotensin-aldosterone system (RAAS), which is exacerbated in COVID-19 infection because the virus binds to the enzyme ACE2, making more angiotensinII available to cause damage.
32721806 Angiotensin-converting enzyme-2 (ACE2) receptor, regulation of the renin-angiotensin-aldosterone system (RAAS), and transmembrane serine protease 2 (TMPRSS2) action are critical for the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) cell entry and infectivity.
32726128 The sex hormone estrogen interacts with the renin-angiotensin-aldosterone system, one of the most critical pathways in COVID-19 infectivity, and modulates the vasomotor homeostasis.
32730512 The renin-angiotensin-aldosterone system (RAAS) is the main plasma volume regulator, which maintains cardiovascular and hydrosaline homeostasis.
32736906 The rationale, concerns, and possible side effects of specific therapeutic measures, including anticoagulants, renin-angiotensin-aldosterone system inhibitors, and anti-inflammatory/antiviral medications applied to the treatment of COVID-19 are also discussed.
32738257 A role for the renin-angiotensin-aldosterone-system in Severe Acute Respiratory Syndrome-Coronavirus-2 infection and in the development of COronaVIrus Disease-19 disease has generated remarkable concerns among physicians and patients. […] Even though a suggestive pathophysiological link between renin-angiotensin-aldosterone-system and the virus has been proposed, its pathogenic role remains very difficult to be defined. […] Although COronaVIrus Disease-19 targets preferentially older people with high prevalence of hypertension and extensive use of renin-angiotensin-aldosterone-system inhibitors, an independent role for hypertension and its therapies is not defined. […] We conclude that at this time, the overall available evidence fails to support a pathogenetic speaks against any harmful role for of renin-angiotensin-aldosterone-system inhibitors in COronaVIrus Disease-19. […] Consequently, we conclude that treatment with renin-angiotensin-aldosterone-system inhibitors should not be discontinued and, therefore, these therapies should not be interrupted.
32739908 The mechanisms of vascular complications are complex and affect both the hemostatic system and immune responses, “inflammatory storm”, disorders of the renin-angiotensin-aldosterone system, endotheliopathy, etc.
32753148 Upregulation of ACE2 mediates conversion of angiotensin II (vasoconstrictor) to angiotensin-(1-7) (vasodilator) and contributes to relatively low blood pressures, despite upregulation of other components of the renin-angiotensin-aldosterone system.
32777758 Proposed aetiologies include hypovolemia, hemodynamic disturbance and inflammation but also specific factors like direct viral invasion, microvascular thrombosis, and altered regulation of the renin-angiotensin-aldosterone system.
32786343 Immune system and renin-angiotensin-aldosterone system dysregulation with associated cytokine release syndrome may be a key feature of early stage of SARS-CoV-2 organotropism and infection.
32788834 The ongoing pandemic has stimulated study of the Renin Angiotensin Aldosterone System (RAAS), and how it can be manipulated to treat COVID-19. […] We detail the Physiology and Pharmacology of the RAAS including the effects of aldosterone and atrial natriuretic peptide.
32791497 In this perspective, we will address the inherent immunological perturbations and alterations in the renin-angiotensin-aldosterone system in patients with obesity and COVID-19, and discuss how these impairments may underlie the increased susceptibility and more detrimental outcomes of COVID-19 in people with obesity.
32791552 As there is no evidence that inhibition of the renin-angiotensin-aldosterone-system is harmful in COVID-19, therapy should be continued as indicated in hypertension or heart failure patients.
32809116 In this paper, we also review the pathogenesis of SARS-CoV-2 infection and how it worsens CVD and postulate that the differences in modulation of the renin-angiotensin-aldosterone system (RAAS) axis which controls angiotensin-converting enzyme (ACE)/ACE2 balance may be an important determinant of COVID-19 outcomes in Africa.
32815593 In this article, the relationship between the Adrenergic system and the renin-angiotensin-aldosterone system (RAAS) is focused in COVID-19 and a vicious circle consisting of the Adrenergic system-RAAS-Angiotensin converting enzyme 2 (ACE2)-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (which is referred to as the “ARAS loop”) is proposed.
32818905 ACE2 regulates the protective arm of the renin-angiotensin-aldosterone system (RAAS) that endows anti-hypertensive and anti-inflammatory effects in the cardiovascular and pulmonary systems.
32825954 The interference on renin-angiotensin-aldosterone system (RAAS) activation, heme formation, and the immune response is responsible for infection diffusion, endothelial dysfunction, vasoconstriction, oxidative damage and releasing of inflammatory mediators.
32830286 The role of renin-angiotensin-aldosterone system (RAAS) inhibitors, notably angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARBs), in the COVID-19 pandemic has not been fully evaluated.
32834792 •There is a concern that renin-angiotensin-aldosterone system (RAAS) blockers increase susceptibility to coronavirus 2019 (COVID-19).
32835316 In patients with serial ECGs, there was no significant change in the QTc interval in prespecified subgroups of interest, including those with prevalent cardiovascular disease or baseline use of renin-angiotensin-aldosterone axis inhibitors.
32848769 The renin-angiotensin-aldosterone system (RAAS) component ACE2 and DPP4 are proteins dysregulated in diabetes.
32852721 There are several controversial hypotheses on the potentially harmful or beneficial effects of antihypertensive drugs acting on the renin-angiotensin-aldosterone system (RAAS) in coronavirus disease 2019 (COVID-19).
32853823 The problem here is that in addition to be a receptor for the SARS-CoV-2 entry into the host cells, ACE2 acts as a key component of the renin-angiotensin-aldosterone system (RAAS) aimed at the generation of a cascade of vasoactive peptides coordinating several physiological processes. […] Since intrinsic disorder might play a role in the functionality of query proteins and be related to the COVID-19 pathogenesis, this work represents an important disorder-based outlook of an interplay between the renin-angiotensin-aldosterone system and SARS-CoV-2.
32864784 Therefore, the use of renin-angiotensin-aldosterone system inhibitors (RASis) in COVID-19 patients could be hypothetically considered, though sufficient evidence is not presented by the scientific community.
32872736 Since the onset of the coronavirus disease 2019 (COVID-19) pandemic, there have been concerns about the association between exposure to renin-angiotensin-aldosterone system (RAAS) inhibitors and the risk and severity of COVID-19.
32875490 While the potential for benefit with the use of renin-angiotensin-aldosterone system inhibitors (RAASi) and the risks from stopping them is more evident, potential harm by RAΑSi may also be caused by the increase in the activity of the ACE2 receptor, the inefficient counter regulatory axis in the lungs in which the proinflammatory prolyloligopeptidase (POP) is the main enzyme responsible for the conversion of deleterious angiotensin (ANG) II to protective ANG [1-7] and the proinflammatory properties of ACE2(+) cells infected with SARS-CoV-2.
32877500 This position statement of the Department of Hypertension of the Brazilian Society of Nephrology (SBN) addresses the controversy surrounding the use or suspension/replacement of the renin-angiotensin-aldosterone system blockers (particularly inhibitors of the angiotensin-converting enzyme or angiotensin II AT1 receptor blockers) prophylactically in individuals using these drugs, due to the possibility of allegedly worsening the prognosis of hypertensive patients infected with SARS-CoV-2.
32899833 In this line, activation of the non-canonical pathway of the renin-angiotensin-aldosterone system (RAAS) could improve CV homeostasis under COVID-19.
32901615 Marked inflammatory process found in severe forms of COVID-19, the complement activation, the cytokine storm, and disruption of the renin-angiotensin-aldosterone system are involved in the onset of thrombotic microangiopathy and large vessel coagulopathy.
32908071 The impaired regulation of renin-angiotensin-aldosterone system (RAAS) has been seen in COVID-19 patients, but whether RAAS inhibitors, such as angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II type 1 receptor blockers (ARBs), are responsible for worsening of clinical conditions remains unknown.
32917504 We hypothesized that the renal abundance of angiotensin-converting enzyme (ACE) 2, the cell surface receptor for SARS-CoV-2, may be modulated by diabetes and agents that block the renin-angiotensin-aldosterone system (RAAS).
32922297 ACE2 serves as an endogenous inhibitor of inflammatory signals associated with four major regulator systems: the renin-angiotensin-aldosterone system (RAAS), the complement system, the coagulation cascade, and the kallikrein-kinin system (KKS).
32926815 Renin-angiotensin-aldosterone system inhibitors and risk of Covid-19.
32928868 More studies reported upregulation than downregulation with ACE-I (n=22), ARBs (n=55), insulin (n=8), thiazolidinedione (n=7) aldosterone agonists (n=3), statins (n=5), oestrogens (n=5) calcium channel blockers (n=3) glucagon-like peptide 1 (GLP-1) agonists (n=2) and Non-steroidal anti-inflammatory drugs (NSAIDs) (n=2).
32933039 In COVID-19 patients, aldosterone via angiotensin-converting enzyme-2 deregulation may be responsible for systemic and pulmonary vasoconstriction, inflammation, and oxidative organ damage. […] Group A (n = 39) were given vasodilator agents or renin-angiotensin-aldosterone system (RAAS) inhibitors and group B (n = 30) were given canrenone i.v.
32935928 SARS-CoV-2 can cause CVD by inducing cytokine storms, creating an imbalance in the oxygen supply and demand and disrupting the renin-angiotensin-aldosterone system; SARS-CoV-2 infection can also lead to the development of CVD through the side effects of therapeutic drugs, psychological factors, and aggravation of underlying CVD.
32943474 Controversies of renin-angiotensin-aldosterone system inhibitors usage in patients with COVID-19 and meticulous handling of case with acute coronary syndrome categorically stresses cardiologists to bust the myths hovering around and set a standard guideline to counterfeit the fatality with timely diagnosis and treatment of COVID-19-induced ACI.
32949380 Concerns have been raised about the possible harmfulness of angiotensin-converter enzyme inhibitors (ACEi) and aldosterone receptor blockers (ARB) in patients with COVID-19.
32966970 ACE2 is an established component of the ‘protective arm’ of the renin-angiotensin-aldosterone-system (RAAS) that opposes ACE/angiotensin II (ANG II) pressor and tissue remodelling actions.
32967329 Furthermore, vitamin D reduces renin-angiotensin-aldosterone system activation and, consequently, decreases ROS generation and improves the prognosis of SARS-CoV-2 infection.
32968307 All patients received loop diuretics, 97.2% beta-blockers, 64.9% an aldosterone antagonist, 60.9% sacubitril/valsartan (S/V), and 72.2% of the remaining patients were on angiotensin-converting enzyme inhibitor or valsartan therapy.
32969367 BACKGROUND Use of renin-angiotensin-aldosterone system inhibitors in coronavirus disease 2019 (COVID-19) patients lacks evidence and is still controversial.
32981365 ACE2 (angiotensin-converting enzyme 2) is a key component of the renin-angiotensin-aldosterone system.
32984543 There is clear evidence that, by targeting the angiotensin-converting enzyme II (ACE2) -its natural receptor-, SARS-CoV-2 would mainly affect the renin-angiotensin-aldosterone system (RAAS), whose imbalance triggers diverse symptomatology-associated pathological processes.
32992048 The hypothesis that been set forward that use of Renin Angiotensin Aldosterone System (RAAS) inhibitors is associated with COVID-19 severity.
32993622 Abnormalities in the renin-angiotensin-aldosterone system (RAAS), angiotensin-converting enzyme-2 (ACE2) and the androgen-driven transmembrane serine protease 2 (TMPRSS2) have been elicited as key modulators of SARS-CoV-2.
32995920 The last decade was crucial for our understanding of the renin-angiotensin-aldosterone system (RAAS) as a two-axis, counter-regulatory system, divided into the classical axis, formed by angiotensin-converting enzyme (ACE), angiotensin II (Ang II), and the angiotensin type 1 receptor (AT1R), and the alternative axis comprising angiotensin-converting enzyme 2 (ACE2), angiotensin-(1-7) (Ang-(1-7)), and the Mas receptor.
32998337 Multivariate analysis showed that after adjusting for gender (males, OR: 1.5, p = 0.0001), age tertiles (second and third tertiles, OR: 2.0 and 4.7, p = 0.0001), and Charlson Comorbidity Index scores (second and third tertiles, OR: 4.7 and 8.1, p = 0.0001), hypertension was significantly predictive of all-cause mortality when this comorbidity was treated with angiotensin-converting enzyme inhibitors (ACEIs) (OR: 1.6, p = 0.002) or other than renin-angiotensin-aldosterone blockers (OR: 1.3, p = 0.001) or angiotensin II receptor blockers (ARBs) (OR: 1.2, p = 0.035).
33006442 After adjustment, subjects with pre-admission usage of renin-angiotensin-aldosterone system (RAAS) inhibitors (HR = 0.35, 95%CI 0.14-0.86, P = .022) had a lower risk of adverse clinical outcomes, including death, acute respiratory distress syndrome, respiratory failure, septic shock, mechanical ventilation, and intensive care unit admission.
33021511 The role of renin-angiotensin-aldosterone system (RAAS) blockers during the coronavirus disease 2019 (COVID-19) pandemic is a matter of controversies.
33023356 Our findings suggest the protective role of renin-angiotensin-aldosterone system inhibition in patients with high cardiovascular risk affected by COVID-19.
33025652 CCBs showed a similar pattern for immune function (lymphocyte percentage 0.21, 95% CI 0.05 to 0.36; neutrophil percentage -0.23, 95% CI -0.39 to -0.08) but had no effect on TNF-α, as did potassium-sparing diuretics and aldosterone antagonists, and vasodilator antihypertensives.
33031192 Given the relationship of SARS-CoV-2 with the renin angiotensin aldosterone system, further evaluation of angiotensin II for the treatment of COVID-19 related shock is warranted.
33038424 ACE2 expression levels were unaltered by exposures to renin angiotensin aldosterone system inhibitors in diabetic kidney disease.
33039544 Incidentally, the renin-angiotensin-aldosterone system (RAAS) is integral to physiologic control of both ACE and ACE2 expression, and is an essential system utilized by SARS-CoV-2, albeit with varying schools of thought on how it can affect viral entry.
33043967 The role of the renin-angiotensin-aldosterone system in COVID-19 is controversially discussed. […] SARS-CoV-2 enters host cells by binding to angiotensin-converting enzyme 2 and activity of the renin-angiotensin-aldosterone system may affect susceptibility to SARS-CoV-2 infection and outcome of patients with COVID-19. […] In this prospective single-center study, we determined the serum levels of ACE-2, angiotensin II and aldosterone in patients with COVID-19 compared to control patients presenting with similar symptoms in the emergency unit. […] Mean serum concentrations of ACE2, angiotensin II, and aldosterone did not differ between the SARS-CoV-2 positive and the control group. […] In summary, we did not find evidence for altered RAAS activity including angiotensin II, aldosterone, or potassium levels, and blood pressure in patients with COVID-19.
33064080 Despite the rapid ongoing evolution of information about this pandemic, this review aims to highlight cardiovascular pathologies related to COVID-19 as either comorbidities, including concerns and uncertainty regarding the effect of renin-angiotensin-aldosterone system (RAAS) inhibitors on angiotensin conversion enzyme 2, or cardiovascular complications.
33071957 Unexpected hyperkalemia in CS patients under treatment with heparin might be the signal of aldosterone suppression.
33082849 Angiotensin converting enzyme-2 (ACE-2) mediated cellular entry of SARS-Cov2 leads to receptor shedding of ACE-2 and disrupts the renin angiotensin aldosterone axis (RAAS).
33084001 This paper presents a brief overview of the complex interaction between age, hypertension, the renin-angiotensin-aldosterone system (RAAS), inflammation, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection.
33093403 KTRs with AKI had more preexisting renin angiotensin aldosterone system inhibitor use than KTRs without AKI (P = 0.03).
33093945 We provide further support to the theory of renin-angiotensin-aldosterone (RAS) activation, discuss the strengths and weaknesses of implicating RAS involvement and highlight the importance of calculating the transtubular potassium gradient to identify those at risk of hypokalaemia and its complications.
33098835 Bioactive peptides with unique amino acid sequences can mitigate such targets including, type II transmembrane serine proteases (TMPRSS2) inhibition, furin cleavage, and renin-angiotensin-aldosterone system (RAAS) members.
33121978 Antithrombotics (32.5%; n = 37) were most commonly evaluated, followed by pulmonary vasodilators (14.0%; n = 16), renin-angiotensin-aldosterone system-related therapies (12.3%; n = 14), and colchicine (8.8%; n = 10).
33123087 We suggest that increased inflammation, activation of renin-angiotensin-aldosterone system, elevated adipokines and higher ectopic fat may be the factors contributing to the disease severity, in particular deteriorating the cardiovascular and lung function, in obese individuals.
33124029 We further shed light on the role of the renin-angiotensin aldosterone system and its inhibitors in the context of COVID-19 and discuss the potential impact of antiviral and anti-inflammatory treatment options.
33129663 Outcomes among patients with HF were similar, regardless of LVEF or renin-angiotensin-aldosterone inhibitor use.
33138935 The role of treatment with renin-angiotensin-aldosterone system blockers at the onset of COVID-19 infection is not known in the geriatric population.
33146371 Angiotensin converting enzyme (ACE) is well-known for its role in blood pressure regulation via the renin-angiotensin aldosterone system (RAAS) but also functions in fertility, immunity, haematopoiesis and diseases such as obesity, fibrosis and Alzheimer’s dementia.
33153216 Both entry from the luminal and basolateral sides of the renal tubular cells are the possible routes for COVID-19, and the microthrombi associated with severe sepsis and the dysregulated renin-angiotensin-aldosterone system worsen further renal injury in SARS-CoV-2-associated AKI.
33154144 The association between the use of renin-angiotensin-aldosterone (RAAS) inhibitors and the risk of mortality from COVID-19 is unclear.
33171852 The virus SARS-CoV-2 employs the Angiotensin-converting enzyme 2 (ACE2), a component of the RAAS (Renin-Angiotensin-Aldosterone System) system, as a receptor for entry into the cells.
33172748 COVID-19 can cause cardiovascular complications or deterioration of coexisting CVD through direct or indirect mechanisms, including viral toxicity, dysregulation of the renin-angiotensin-aldosterone system (RAAS), endothelial cell damage and thromboinflammation, cytokine storm, and oxygen supply-demand mismatch.
33181156 Receiving immunosuppression or renin-angiotensin-aldosterone system inhibitors at presentation did not increase the risk of death or acute kidney injury in the glomerulonephritis cohort.
33186672 In the present review, we summarize examples underlying fallacious reasoning recommendations regarding treatment with Renin-Angiotensin-Aldosterone inhibitors (RAASi) in the COVID-19 context.
33188364 Angiotensin-converting enzyme 2 (ACE2), which is part of the renin-angiotensin-aldosterone system (RAAS), is the main entry receptor for SARS-CoV-2; although dipeptidyl peptidase 4 (DPP4) might also act as a binding target.
33196058 ACE2 is integral to the renin-angiotensin-aldosterone system (RAAS), and SARS-CoV-2 down-regulates protein expression levels of ACE2.
33202960 These observations implicate an active role of metabolic syndrome, systemic and tissue islet renin-angiotensin-aldosterone system, redox stress, inflammation, islet fibrosis, amyloid deposition along with β-cell dysfunction and apoptosis in those who develop T2DM.
33211434 The breakthrough of the secrets of hypertension and the renin-angiotensin-aldosterone system (RAAS) is one of the legends of medicine. […] The puzzle of this elegant cascade is completed by aldosterone isolation by the collaboration of Tait spouses and Tadeus Rechstein.
33217033 Animal studies suggest that renin-angiotensin-aldosterone system (RAAS) blockers might increase the expression of ACE2 and potentially increase the risk of SARS-CoV-2 infection.
33222412 Renin-angiotensin-aldosterone system inhibitors (RAASi) improve outcomes in cardiorenal disease but concerns have been raised over increased risk of incident hospitalization and death from coronavirus disease 2019 (COVID-19).
33233531 In line with these genetic profiling studies, the broad spectrum of COVID-19 illness could be explained by immuno-pathological regulation of these critical immunogenetic pathways through various epigenetic mechanisms, which further interconnect to other vital components such as those in the renin-angiotensin-aldosterone system (RAAS) because of its direct interaction with the virus causing COVID-19.
33249290 Bronchoalveolar lavage fluid from coronavirus disease-2019 (COVID-19) subjects showed a critical imbalance in the renin-angiotensin-aldosterone system with the upregulated expression of ACE2.
33252294 Estradiol protects the vascular system, mediating with the renin-angiotensin-aldosterone system, whereas testosterone enhances the levels of angiotensin-converting enzyme and the transmembrane protease serine-type 2, thus delaying viral clearance in men as compared to women.
33254506 The angiotensin converting enzyme-2 (ACE-2), a component in the renin-angiotensin-aldosterone system (RAAS), plays as cell surface receptors for SARS-CoV-2.
33254538 We hypothesize that overreaction of the renin-angiotensin-aldosterone may account for the myriad of unusual biochemical and clinical abnormalities noted in patients infected with SARS-CoV-2.
33275540 ACE2 is crucial for maintaining tissue homeostasis and negatively regulates the renin-angiotensin-aldosterone system (RAAS) in humans.
33278189 They are inhibited by protease nexin 1 or serine E2 (PN1) that is upregulated by angiotensin II but downregulated by aldosterone.
33283618 Plasma vitamin D levels and evolutionary adaptations of the renin-angiotensin-aldosterone system (RAAS) in Black people differ considerably from those of other races.
33303654 The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus enters host cells by binding to the angiotensin-converting enzyme 2 (ACE2), but whether or not renin-angiotensin-aldosterone system inhibitors (RAASi) would be beneficial to COVID-19 cases remains controversial.
33304284 By describing ACE2 and the whole Renin Angiotensin Aldosterone System (RAAS) we may better understand whether specific cell types may be affected by SARS-CoV-2 and whether their functioning can be disrupted in case of an infection.
33312744 This activates the renin angiotensin aldosterone mechanism (RAAM).
33321496 AKI in COVID-19 has a multifactorial origin, in which direct viral invasion of kidney cells, activation of the renin-angiotensin aldosterone system, a hyperinflammatory response, hypercoagulability, and nonspecific factors such as hypotension and hypoxemia may be involved.
33327700 Nonetheless, unique features of this pathogen, e.g. direct insult leading to myocarditis and renin-angiotensin-aldosterone axis dysregulation, must be taken into account.
33329934 Direct viral toxicity, pro-inflammatory and pro-thrombotic induction, endothelial damage, immune imbalance, and dysregulation of the renin-angiotensin-aldosterone system are the mechanisms underlying the viral potential of multiple organ damage.
33342421 It should also be considered that all components of the reninangiotensin-aldosterone system (RAAS) are located in the lung tissues.
33364877 The effects of chronic renin-angiotensin-aldosterone system (RAAS) blockers usage on adverse outcomes and disease severity remain uncertain in COVID-19 patients with hypertension.
33375676 Our data show a high prevalence of hypertension, more likely treated with renin-angiotensin-aldosterone system (RASS) inhibitors, among COVID-19 patients not requiring hospitalization.
33378401 Retrospective studies on the use of Renin-Angiotensin-Aldosterone System blockade in patients with Coronavirus Disease 2019 (COVID-19) have been informative but conflicting, and prospective studies are required to demonstrate the safety, tolerability, and outcomes of initiating these agents in hospitalized patients with COVID-19 and hypertension.
33382450 We will review evidence for the role of the renin-angiotensin-aldosterone system (RAAS), the risk of pre-existing cardiovascular disease in COVID-19 susceptibility and course, and the mechanism of acute and long-term myocardial injury.
33387941 Angiotensin-converting enzyme 2 (ACE2), an important component of the renin-angiotensin-aldosterone system (RAAS), displays circadian rhythmicity.
33389262 ACE2 is a key regulator of the renin-angiotensin-aldosterone system (RAAS).
33398362 To date, multiple theories relating to the pure effects of renin-angiotensin-aldosterone system (RAAS) inhibitors on COVID-19 infections have been postulated.
33404127 The role of antihypertensives, especially Renin-Angiotensin-Aldosterone System inhibitors, is still debatable in COVID-19-related severity and outcome.
33404363 In particular, we now better understand the complexity of the renin-angiotensin-aldosterone system (RAAS) and the important role of angiotensin converting enzyme (ACE)-2 in viral binding.
33414726 Literature on COVID-19 highlighted the central role of the Renin Angiotensin Aldosterone System in the determinism of SARS-CoV2 cellular internalization in the target tissues.
33422689 Angiotensin-converting enzyme 2 (ACE2) is an important player of the renin-angiotensin-aldosterone system (RAAS) in regulating the conversion of angiotensin II into angiotensin (1-7).
33423528 After initially hypothesizing a positive relationship between use of renin-angiotensin-aldosterone system inhibitors and risk of coronavirus disease 2019 (COVID-19), more recent evidence suggests negative associations.
33432484 Furthermore, they repair the renin-angiotensin-aldosterone system (RAAS) malfunction, increase alveolar fluid clearance, and reduce the chance of hypercoagulation.
33435650 Herein we discuss the complex interaction between the Renin-Angiotensin-Aldosterone System (RAAS), its receptors, and the interaction with the Kallikrein-Kinin-System (KKS) and the potential activation of the coagulation cascade.
33437743 Therefore, medications acting on renin-angiotensin-aldosterone system can lead to serious complications, especially in patients with diabetes and hypertension.
33438198 Stroke, asthma, chronic obstructive pulmonary disease and treatment with renin-angiotensin-aldosterone inhibitors (RAASi) were independent risk factors of ICU mortality in the pre-specified primary analyses; treatment with statins was protective.
33443121 ACE2 is part of the counter-regulatory renin-angiotensin-aldosterone system and is also expressed in the lower respiratory tract along the alveolar epithelium.
33447763 Emerging epidemiological studies suggested that Renin-Angiotensin-Aldosterone system (RAAS) inhibitors may increase infectivity and severity of COVID-19 by modulating the expression of ACE2.
33448738 Ongoing research investigates potential of anti-viral and anti-inflammatory agents along with safety and efficacy of commonly prescribed drugs such as renin-angiotensin-aldosterone system blockers.
33458761 ACE2 usually converts Angiotensin I in the renin-angiotensin-aldosterone system to Angiotensin II, which affects blood pressure levels.
33462706 CVD diagnoses, use of renin-angiotensin-aldosterone system (RAAS) antagonists: ACEi, ARBs, and aldosterone antagonists, were ascertained.
33463113 We then present a comprehensive view on host cells and the significance of gene variants affecting activation enzymes, supportive entry, and spread mechanisms in humans including renin-angiotensin-aldosterone system (RAAS) a pathway results in certain phenotypes or exacerbate infection-related phenotypes in different organs, hence causes variable clinical manifestations.
33477294 It has been proposed that spironolactone may prevent acute lung injury in COVID-19 infection due to its pleiotropic effects with favorable renin-angiotensin-aldosterone system (RAAS) and ACE2 expression, reduction in transmembrane serine protease 2 (TMPRSS2) activity and antiandrogenic action, and therefore it may prove to act as additional protection for patients at highest risk of severe pneumonia.
33507655 Finally, renin-angiotensin-aldosterone inhibitors do not appear to increase the risk of an infection by COVID-19.
33519802 This viewpoint presents: (1) a brief introduction regarding the renin-angiotensin-aldosterone system (RAAS), detailing its receptors, molecular synthesis, and degradation routes; (2) a description of the proposed early changes in the RAAS in response to SARS-CoV-2 infection, including biological scenarios for the best and worst prognoses; and (3) the physiological pathways and reasoning for changes in the RAAS following SARS-CoV-2 infection.
33520683 This present review aims to comprehensively summarize the up-to-date scientific literatures on biological activities of plant- and mushroom-derived compounds relevant to mechanistic targets involved in SARS-CoV-2 infection and inflammatory-associated pathogenesis, including viral entry, replication and release, and the renin-angiotensin-aldosterone system (RAAS). studies were excluded. molecular docking analysis, herein, we provide a total of 150 natural compounds as potential candidates for development of new anti-COVID-19 drugs with higher efficacy and lower toxicity than the existing therapeutic agents.
33525440 During transmission, the renin-aldosterone-angiotensin-system (RAAS) is involved with the spike protein of SARS-CoV-2, attaching to its natural receptor angiotensin-converting enzyme 2 (ACE 2) in host cells.
33537555 The renin-angiotensin-aldosterone system (RAAS) is strictly involved in COVID-19 because angiotensin converting enzyme 2 (ACE2) is the host receptor for SARS-CoV-2 and also converts pro-inflammatory angiotensin (Ang) II into anti-inflammatory Ang(1-7).
33539316 Objective While evidence on the interface between severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection and the renin-angiotensin-aldosterone-system (RAAS) is accumulating, clinical data on RAAS peptide alteration among coronavirus disease-19 (COVID-19) patients is missing.
33542445 These drugs include chloroquine (CQ), hydroxychloroquine (HCQ), azithromycin, lopinavir/ritonavir (LPV/r), atazanavir (ATV), favipiravir (FVP), nevirapine (NVP), efavirenz (EFV), oseltamivir, remdesivir, anakinra, tocilizumab (TCZ), eculizumab, heme oxygenase 1 (HO-1) regulators, renin-angiotensin-aldosterone system (RAAS) inhibitors, ivermectin, and nitazoxanide.
33544293 Aiming to show clinical outcome of renin-angiotensin-aldosterone system blockers in hospital treatment of hypertensive patients with coronavirus disease 2019, systematically searched literatures through five databases were intensively appraised using The Grading of Recommendations Assessment, Development and Evaluation checklists for cohort studies.
33546734 The aim of the RAAS-COVID-19 randomized control trial is to evaluate whether an upfront strategy of temporary discontinuation of renin angiotensin aldosterone system (RAAS) inhibition versus continuation of RAAS inhibition among patients admitted with established COVID-19 infection has an impact on short term clinical and biomarker outcomes.
33563197 Even though ACE-2 is significant in the renin-angiotensin-aldosterone system (RAAS) regulation that exhibits protection to various organs, they play a significant role in COVID-19 disease pathogenesis.
33564823 A growing number of observational studies evaluating the effects of certain drugs have been conducted, including several assessing whether hydroxychloroquine improves outcomes in infected individuals and whether renin-angiotensin-aldosterone system inhibitors have detrimental effects.
33584343 ACE2 has extensive biological activities as a component of the renin-angiotensin-aldosterone system (RAAS) and plays a pivotal role as counter-regulator of angiotensin II (Ang II) activity by converting the latter to Ang (1-7).
33584499 Although traditionally a rare condition, PRES is likely to be more common among patients with COVID-19 pathobiology there is Renin downregulation of ACE2 receptors, involvement of Renin-Angiotensin-Aldosterone system, endotheliitis, cytokine storm, and hyper-immune response.
33587202 Our results suggest that previously reported associations of COVID-19 mortality with body mass index, low vitamin D, air pollutants, renin-angiotensin-aldosterone system inhibitors may be explained by the aforementioned factors.