scholarly journals Impact of renin-angiotensin system inhibitors and beta-blockers on dental implant stability

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Babak Saravi ◽  
Andreas Vollmer ◽  
Gernot Lang ◽  
Nicholai Adolphs ◽  
Zhen Li ◽  
...  
Keyword(s):  
Bone Remodeling ◽  
Dental Implant ◽  
Antihypertensive Medication ◽  
Beta Blockers ◽  
Renin Angiotensin System ◽  
Implant Stability ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
The Impact ◽  
Ras Inhibitors

Abstract Background Current experimental research suggests antihypertensive medication reduces the failure risk of dental implants due to enhanced bone remodeling. However, evidence from clinical studies evaluating the impact of antihypertensive medication on implant stability is lacking. Methods We retrospectively analyzed 377 implants in 196 patients (46 implants inserted in antihypertensive drug users (AH) and 331 implants in non-users (NAH)) for implant stability measured by radiofrequency analysis, and we determined the implant stability quotient (ISQ). AH subgroups were stratified by the use of beta-blockers, renin-angiotensin system (RAS) inhibitors, and both of the aforementioned. The impact of antihypertensive medication on ISQ values at implant insertion (primary stability) and implant exposure (secondary stability) was analyzed by a linear regression model with a regression coefficient and its 95% confidence interval (95% CI), adjusted for potential confounders. Results Time between implant insertion and implant exposure was 117.1 ± 56.6 days. ISQ values at insertion were 71.8 ± 8.7 for NAH and 74.1 ± 5.6 for AH, respectively. ISQ at exposure was 73.7 ± 8.1 for NAH and 75.7 ± 5.9 for AH. Regression analysis revealed that none of the AH subgroups were significantly related to ISQ at implant insertion. However, renin-angiotensin system inhibitors (RAS) were significantly associated with higher ISQ values at exposure (reg. coeff. 3.59, 95% CI 0.46–6.71 (p=0.025)). Conclusions Outcome of the present study indicates enhanced bone remodeling and osseointegration following dental implant insertion in patients taking RAS inhibitors than in non-users. Future randomized prospective studies must confirm these indicative results.

scholarly journals Renin Angiotensin System Inhibition and Susceptibility and Outcomes from COVID-19: A Systematic Review and Meta-analysis of 69,200 COVID-19 Patients

2020 ◽  
Author(s):  
Yi Zhang ◽  
Shikai Yu ◽  
Yawei Xu ◽  
Bryan Williams
Keyword(s):  
Systematic Review ◽  
Observational Studies ◽  
Meta Analysis ◽  
Renin Angiotensin System ◽  
Risk Of Infection ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Significant Difference ◽  
The Impact ◽  
Ras Inhibitors

ABSTRACTBackgroundEarly observational studies suggested that the use of the renin angiotensin system (RAS) inhibitors, specifically angiotensin converting enzyme inhibitors or angiotensin receptor blockers, may increase the risk of infection with SARS-CoV-2 and adversely affect the prognosis or survival of infected patients. To explore the impact of RAS inhibitor use on the risk of SARS-CoV-2 infection and the prognosis of SARS-CoV-2 infected patients, from all published studies.Methods and FindingsA systematic review and meta-analysis of the use of RAS inhibitors in relation to infection with SARS-CoV-2 and/or the severity and mortality associated with COVID-19 was conducted. English language bibliographic databases PubMed, Web of Science, OVID Embase, Scopus, MedRxiv, BioRxiv, searched from Jan 1st, 2020 to July 20th, 2020. 58 observational studies (69,200 COVID-19 patients and 3,103,335 controls) were included. There was no difference in the susceptibility to SARS-CoV-2 infection between RAS inhibitor users and non-users (unadjusted OR 1.05, 95% CI 0.90 to 1.21), (adjusted OR 0.93, 95% CI 0.85 to 1.02), (adjusted HR 1.07, 95% CI 0.87 to 1.31). There was no significant difference in the severe Covid-19 case rate between RAS inhibitor users and non-users (unadjusted OR 1.05, 95% CI 0.81 to 1.36), (adjusted OR 0.76, 95% CI 0.52 to 1.12), or in mortality due to COVID-19 between RAS inhibitor users and non-users (unadjusted OR 1.12, 95% CI 0.88 to 1.44), (adjusted OR 0.97, 95% CI 0.77 to 1.23), (adjusted HR 0.62, 95% CI 0.34 to 1.14).ConclusionsIn the most comprehensive analysis of all available data to date, treatment with RAS inhibitors was not associated with increased risk of infection, severity of disease, or mortality due to COVID-19. The best available evidence suggests that these treatments should not be discontinued on the basis of concern about risk associated with COVID-19.

P5448Enzymatic regulation of the myocardial tissue renin-angiotensin-system of the failing heart

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
H Arfsten ◽  
N Pavo ◽  
R Wurm ◽  
S Prausmueller ◽  
G Spinka ◽  
...  
Keyword(s):  
Renin Angiotensin System ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Failing Heart ◽  
Conversion Rates ◽  
Neprilysin Inhibitor ◽  
Metabolic Activities ◽  
End Stage ◽  
The Impact ◽  
Ras Inhibitors

Abstract Background In heart failure with reduced ejection fraction (HFrEF) the renin-angiotensin-system (RAS) is dysregulated and serves as therapeutic target. Research has been focusing on plasma RAS. Information on tissue RAS is scarce although assumedly more crucial for myocardial function. Among known angiotensins, only AngII and AngIII are detectable in the failing heart. Plasma samples in HFrEF show high AngI and AngII levels with clearly distinguishable AngI/AngII ratios for different RAS-inhibitors. AngII and AngIII levels in the myocardium were comparable for different RAS-inhibitors, i.e. no RAS-blocker, ACE-inhibitor, ARB or angiotensin-receptor neprilysin-inhibitor (ARNI). Here we aimed to elucidate the metabolic regulation of tissue RAS enzymes for these four different modalities of RAS-inhibition. Methods Enzyme regulation and metabolic activities were investigated in myocardial samples of end-stage HFrEF patients undergoing heart transplantation with a mass-spectrometry based method. Concentrations of respective angiotensin metabolites AngI, AngII, Ang1–7, AngIII, Ang1–5 and AngIV (RAS-fingerprints) were investigated after adding AngI or AngII and incubation to display metabolic patterns of the main plasma angiotensins. Metabolic activities of distinct enzymes have been assessed for the no therapy and ACE-I subgroups. Patients were stratified according to background therapy with RAS-inhibitors. Results A total of 30 patients were included (n=6 without RAS-blockade, n=16 with ACE-I, n=6 with ARB, n=2 with ARNI). Median age was 55 (IQR 45–63) years, 87%were male. Etiology of HF was ischemic in 40%, median NT-proBNP levels were 3498pg/ml (IQR 1761–8400). Patterns for tissue RAS metabolism of AngI and AngII was visually similar for all groups, indicating comparable regulation of tissue RAS enzymes independent from therapy (Figure 1). The formation of AngII from AngI was mainly chymase dependent with conversion rates of 99.4 (IQR 77.0–254.1) (pg/μg protein)/h for ACE-I and 141.8 (IQR 67.9–369.2) (pg/μg protein)/h for no RAS-blockade, whereas ACE-related generation of AngII was under the detection limit. The formation of Ang1–7 from AngI was mediated by NEP and PEP. The contribution of NEP was significantly higher [5022 (IQR 5002–5286) (pg/μg)/h vs 3555 (IQR 3351–3849) (pg/μg)/h, p=0.005 for the ACE-I group and 4729 (IQR 4438–6135) (pg/μg)/h vs 3601 (IQR 3052–4182) (pg/μg)/h, p=0.012 for no RAS-blockade]. No differences in tissue enzymatic activities between ACE-I and no therapy, as already indicated by the metabolization patterns occurred. Figure 1 Conclusions Enzymatic tissue RAS regulation in end-stage HF seems to be independent from the mode of established RAS-inhibitor therapy.In contrast to plasma, AngII formation of the tissue is mainly chymase dependent, whereas ACE seems to play an unsignificant role. NEP has a substantial role in generating beneficial Ang1–7 from AngI. The impact of NEP inhibition by ARNI on tissue RAS and mechanism of action have to be further investigated.

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.

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’.

Abstract 13174: Sex Differences in Clinical Characteristics, Management and Prognosis in Patients With Heart Failure With Preserved Ejection Faction: Insights From the CHART-2 Study

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Kanako Tsuji ◽  
Yasuhiko Sakata ◽  
Masanobu Miura ◽  
Soichiro Tadaki ◽  
Ryoichi Ushigome ◽  
...  
Keyword(s):  
Heart Failure ◽  
Sex Differences ◽  
Beta Blockers ◽  
Renin Angiotensin System ◽  
Class Iii ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Female Patients ◽  
Increased Risk ◽  
Patients With Heart Failure

Background: The number of the patients with heart failure with preserved ejection fraction (HFpEF) has been rapidly increasing worldwide. However, sex differences in patients with HFpEF remain to be elucidated. Methods and Results: We examined sex differences in 3,124 consecutive patients with HFpEF (EF≥50%, mean 69.4years, 34.7% female) registered in our Chronic Heart Failure Analysis and Registry in the Tohoku District-2 (CHART-2) Study (N=10,219). Female patients, as compared with male patients, were characterized by higher age (72 vs. 68 years, P<0.01), higher LVEF (67 vs. 64%, P<0.01), higher heart rate (74 vs. 70bpm, PNYHA class III (14.1 vs. 7.0%, P<0.01), higher BNP levels (106 vs. 73pg/mL, P<0.01), lower prevalence of coronary artery disease (30 vs. 53%, P<0.01) and lower prescription rates of renin angiotensin system inhibitors (64.7 vs. 71.8%, P<0.01) and beta-blockers (37.8 vs. 43.9%, P<0.01). During the median 3.2-year follow-up, 147 female patients and 245 males died. Although there was no sex difference in all-cause mortality (13.6 vs. 12.0%, P=0.11), female patients more frequently died due to cardiovascular causes (53.7 vs. 39.2%, hazard ratio (HR): 1.62, 95% CI 1.20-2.18, P<0.01), and experienced more HF admissions (12.6 vs. 9.8%, HR: 1.35, 95% CI 1.08-1.68, P<0.01). Use of beta-blockers or renin-angiotensin system inhibitors was not associated with decreased incidence of death or HF admission in both sexes. In contrast, use of statins was associated with reduced incidence of all-cause death in both sexes (males and females; adjusted HR, 0.59 and 0.57; 95% CI 0.46-0.77 and 0.47-0.70, respectively, both P<0.01) and was also associated with reduced incidence of HF admission in males (adjusted HR: 0.67, 95%CI 0.53-0.85, P<0.01) but not in females (adjusted HR: 0.83, 95% CI 0.63-1.10, P=0.19). Conclusions: As compared with males, female patients with HFpEF were characterized by severer condition of HF and increased risk of cardiovascular death and HF admission. Although statin use was equally associated with improved mortality in both sexes, female patients with HFpEF may benefit from statins less than males in terms of reduction of HF admission.

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.

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