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Hypertension Research : Official... Jun 2024There is insufficient evidence that angiotensin-converting enzyme inhibitors (ACEIs) can reduce pneumonia by inducing a dry cough that confers a protective effect on the...
Risk of pneumonia-related hospitalization after initiating angiotensin-converting enzyme inhibitors compared with angiotensin II receptor blockers: a retrospective cohort study using LIFE Study data.
There is insufficient evidence that angiotensin-converting enzyme inhibitors (ACEIs) can reduce pneumonia by inducing a dry cough that confers a protective effect on the airway. To increase the evidence base on the clinical use of ACEIs for pneumonia prevention, this retrospective cohort study aimed to comparatively examine the risk of pneumonia-related hospitalization between ACEI initiators and angiotensin II receptor blocker (ARB) initiators using claims data from two Japanese municipalities. We identified persons who were newly prescribed any ACEI or ARB as their first antihypertensive agent between April 2016 and March 2020. The Fine-Gray method was applied to a Cox proportional hazards model to estimate the subdistribution hazard ratio (HR) of ACEI use (reference: ARB use) for pneumonia-related hospitalization, with death treated as a competing risk. Sex, age, comorbidities, medications, and pneumococcal immunization were included as covariates. The analysis was conducted on 1421 ACEI initiators and 9040 ARB initiators, and the adjusted subdistribution HR of ACEI use was estimated to be 1.21 (95% confidence interval: 0.89-1.65; P = 0.22). ACEI initiation did not demonstrate any significant preventive effect against pneumonia-related hospitalization relative to ARB initiation. There remains a lack of strong evidence on the protective effects of ACEIs, and further research is needed to ascertain the benefits of their use in preventing pneumonia. We conducted a large-scale retrospective cohort study using real-world healthcare data from a Japanese population. In this study, ACEI initiation did not indicate a significant preventive effect against pneumonia-related hospitalization.
PubMed: 38942815
DOI: 10.1038/s41440-024-01768-7 -
Progress in Molecular Biology and... 2024Cardiovascular diseases (CVDs) are characterized by abnormalities in the heart, blood vessels, and blood flow. CVDs comprise a diverse set of health issues. There are... (Review)
Review
Cardiovascular diseases (CVDs) are characterized by abnormalities in the heart, blood vessels, and blood flow. CVDs comprise a diverse set of health issues. There are several types of CVDs like stroke, endothelial dysfunction, thrombosis, atherosclerosis, plaque instability and heart failure. Identification of a new drug for heart disease takes longer duration and its safety efficacy test takes even longer duration of research and approval. This chapter explores drug repurposing, nano-therapy, and plant-based treatments for managing CVDs from existing drugs which saves time and safety issues with testing new drugs. Existing drugs like statins, ACE inhibitor, warfarin, beta blockers, aspirin and metformin have been found to be useful in treating cardiac disease. For better drug delivery, nano therapy is opening new avenues for cardiac research by targeting interleukin (IL), TNF and other proteins by proteome interactome analysis. Nanoparticles enable precise delivery to atherosclerotic plaques, inflammation areas, and damaged cardiac tissues. Advancements in nano therapeutic agents, such as drug-eluting stents and drug-loaded nanoparticles are transforming CVDs management. Plant-based treatments, containing phytochemicals from Botanical sources, have potential cardiovascular benefits. These phytochemicals can mitigate risk factors associated with CVDs. The integration of these strategies opens new avenues for personalized, effective, and minimally invasive cardiovascular care. Altogether, traditional drugs, phytochemicals along with nanoparticles can revolutionize the future cardiac health care by identifying their signaling pathway, mechanism and interactome analysis.
Topics: Humans; Drug Repositioning; Drug Discovery; Animals; Heart Diseases
PubMed: 38942536
DOI: 10.1016/bs.pmbts.2024.02.001 -
American Journal of Respiratory and... Jun 2024Sarcoidosis is a granulomatous disorder of unclear cause notable for abnormal elevation of blood and tissue angiotensin converting enzyme 1 (ACE1) levels and activity....
Sarcoidosis is a granulomatous disorder of unclear cause notable for abnormal elevation of blood and tissue angiotensin converting enzyme 1 (ACE1) levels and activity. ACE1 regulates the renin-angiotensin-aldosterone system (RAAS), the terminal product of which is aldosterone, which selectively engages mineralocorticoid receptors (MR) to promote inflammation. We sought to determine whether the RAAS promotes sarcoidosis granuloma formation and related inflammatory responses. Using an established model, we first determined whether aldosterone was produced by sarcoidosis granulomas and verified the presence of CYP11B2, the enzyme required for its production. We then evaluated the effects of selective inhibitors of ACE1 (captopril), angiotensin type 1 receptor (losartan) and MR (spironolactone, eplerenone) on granuloma formation, reflected by computer image analysis-generated granuloma area, and selected cytokines incriminated in sarcoidosis pathogenesis. Aldosterone was spontaneously produced by sarcoidosis PBMCs, and both intra- and extracellular levels steadily increased during granuloma formation. In parallel, PBMCs were shown to express more CYP11B2 during granuloma formation. Significant inhibition of sarcoidosis granulomas and related cytokines (TNFα, IL-1β, IFNγ, IL-10) was observed in response to pretreatments with captopril, losartan, spironolactone or eplerenone, comparable to that of prednisone. The RAAS is intact in sarcoidosis granulomas and contributes significantly to early granuloma formation and to related inflammatory mediator responses with important implications for clinical management.
PubMed: 38941161
DOI: 10.1164/rccm.202402-0265OC -
Annals of Ibadan Postgraduate Medicine Apr 2024A major modifiable risk factor for atherosclerotic cardiovascular disease is abnormalities in lipid and lipoprotein metabolism which are frequently seen in HIV as well...
BACKGROUND AND OBJECTIVE
A major modifiable risk factor for atherosclerotic cardiovascular disease is abnormalities in lipid and lipoprotein metabolism which are frequently seen in HIV as well as its treatment. Apo-E is a protein that is important in plasma lipid homeostasis and its genetic alleles have been shown to contribute to lipid abnormalities. We examined for the effect of Apo-E gene polymorphisms on plasma lipid levels in PLHIV on protease inhibitor therapy.
METHODS
This was a cross-sectional study conducted among adult persons living with HIV. Lipid profile, Apo-B and Apo-A were measured in fasting plasma. Amplification and analysis of Apo-E genotypes were determined using the Seeplex Apo-E ACE genotyping kit. Differences in quantitative values were compared with non-parametric analysis methods.
RESULTS
Eighty-four persons were recruited into the study, 75% of whom were virally suppressed. The 3 homozygous genotypes had significantly different levels of low-density lipoprotein cholesterol (LDL-C), Apolipoprotein B (Apo-B) and Apolipoprotein A1 (Apo-A1). Persons with apo ε2/ε2 had higher LDL-C compared to those with apo ε3/ε3 (3.26 (3.61) mmol/L vs. 2.76 (1.28) mmol/L, p = 0.010). Those with apo ε4/ε4 had lower Apo-A1 compared to those with apo ε3/ε3 (0.84 (0.48) g/dL vs. 1.27 (0.70) g/dL, p =0.009). Compared with the same group, the heterozygous genotype, apo ε2/ε3 had lower triglyceride levels :1.33 (0.65) mmol/ L vs. 1.86 (1.11) mmol/L, p = 0.045.
CONCLUSION
Polymorphisms in the Apo-E gene may have significant influences on plasma lipid and apolipoprotein levels in PLHIV on PI therapy. This may have implications for the assessment of risk for cardiovascular disease.
PubMed: 38939889
DOI: No ID Found -
JACC. Advances May 2024Persistent left ventricular hypertrophy after transcatheter aortic valve replacement (TAVR) has been associated with poor outcomes. Angiotensin-converting enzyme...
BACKGROUND
Persistent left ventricular hypertrophy after transcatheter aortic valve replacement (TAVR) has been associated with poor outcomes. Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), due to their favorable effects on ventricular remodeling, have been hypothesized to improve outcomes post-TAVR, yet there are no recommendations regarding their use.
OBJECTIVES
This study aimed to compare the outcomes of patients receiving ACEIs/ARBs with those not receiving ACEIs/ARBs after TAVR.
METHODS
We performed a literature search on PubMed and Cochrane Library until June 14, 2023, and included all studies comparing clinical outcomes between patients given ACEIs/ARBs and those not given ACEIs/ARBs after TAVR. All-cause mortality was the primary outcome. We used a random effects model with appropriate corrections to calculate relative risk (RR) and CIs, with all analyses carried out using R v4.0.3.
RESULTS
We included ten studies on the use of ACEIs/ARBs post-TAVR. Patients on ACEIs/ARBs had lower risk of all-cause mortality (RR: 0.74, 95% CI: 0.65-0.86, I = 62%, chi-square < 0.01), cardiovascular mortality (RR: 0.70, 95% CI: 0.56-0.88, I = 0%, chi-square = 0.54), and new-onset atrial fibrillation (RR: 0.71, 95% CI: 0.52-0.96, I = 0%, chi-square = 0.59). Patients on ACEIs/ARBs had a similar risk of myocardial infarction, heart failure, stroke, new permanent pacemaker implantation, acute kidney injury, major bleeding, vascular complications, aortic regurgitation, and mitral regurgitation.
CONCLUSIONS
We found that patients receiving ACEIs/ARBs had a lower risk of all-cause mortality, cardiovascular mortality, and new-onset atrial fibrillation. Risk of other outcomes was similar to patients not receiving ACEIs/ARBs. Randomized clinical trials are needed to explore the benefits of ACEIs/ARBs post-TAVR, so that definitive guidelines can be developed.
PubMed: 38939627
DOI: 10.1016/j.jacadv.2024.100927 -
JACC. Advances Jun 2023Recent trial data refute concerns about neurocognitive off-target effects of neprilysin inhibition with sacubitril and suggest benefit in patients with heart failure and...
BACKGROUND
Recent trial data refute concerns about neurocognitive off-target effects of neprilysin inhibition with sacubitril and suggest benefit in patients with heart failure and ejection fraction >40%. We hypothesized that sacubitril/valsartan is associated with improved cognitive outcomes in patients with heart failure and reduced ejection fraction (HFrEF).
OBJECTIVES
The purpose of this study was to compare 3-year cognitive outcomes in patients with HFrEF who receive sacubitril/valsartan vs angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs).
METHODS
Retrospective cohort study of: 1) 11,313 adults with HFrEF (International Classification of Diseases-10th Revision-Clinical Modification [ICD-10-CM] codes: I50.2 or I50.4) started on sacubitril/valsartan between 1/1/2015 and 12/31/2019; and 2) 11,313 propensity matched patients receiving ACEI/ARB during that time. Data were obtained from the TriNetX Research Network, encompassing 41 health care organizations in the United States. Primary endpoint was the composite of cognitive decline (ICD-10-CM: R41.8), dementia (ICD-10-CM: F01-F03), and Alzheimer's disease (ICD-10-CM: G30).
RESULTS
At 3 years, 858 patients on sacubitril/valsartan met the primary endpoint vs 1,209 on ACEI/ARB (3-year incidence: 10.7% vs 15.0%; HR: 0.69; 95% CI: 0.63-0.75; < 0.001), with consistently lower rates of cognitive decline (9.5% vs 13.3%; HR: 0.69; 95% CI: 0.63-0.76; < 0.001), dementia (3.4% vs 5.0%; HR: 0.65; 95% CI: 0.57-0.77; < 0.001), and Alzheimer's disease (0.6% vs 1.3%; HR: 0.48; 95% CI: 0.35-0.66; < 0.001) in the sacubitril/valsartan cohort. Results were consistent in matched sex and race subgroups. Three-year mortality was 22.0% on sacubitril/valsartan vs 24.6% on ACEI/ARB (HR: 0.89; 95% CI: 0.84-0.94; < 0.001).
CONCLUSIONS
Sacubitril/valsartan was associated with lower 3-year rates of neurocognitive disorders when compared to ACEI/ARBs in patients with HFrEF.
PubMed: 38938237
DOI: 10.1016/j.jacadv.2023.100372 -
Kidney Research and Clinical Practice Jun 2024Acute kidney disease (AKD) is a critical transitional period between acute kidney injury and chronic kidney disease. The incidence of AKD following acute kidney injury...
Acute kidney disease (AKD) is a critical transitional period between acute kidney injury and chronic kidney disease. The incidence of AKD following acute kidney injury is approximately 33.6%, and it can occur without identifiable preceding acute kidney injury. The development of AKD is associated with increased risks of chronic kidney disease, dialysis, and mortality. Biomarkers and subphenotypes are promising tools to predict prognosis in AKD. The complex clinical situations in patients with AKD necessitate a comprehensive and structured approach, termed "KAMPS" (kidney function check, advocacy, medications, pressure, sick day protocols). We introduce "MAND-MASS," an acronym devised to summarize the reconciliation of medications during episodes of acute illness, as a critical component of the sick day protocols at AKD. A multidisciplinary team care, consisting of nephrologists, pharmacists, dietitians, health educators, and nurses, is an optimal model to achieve the care bundle in KAMPS. Although the evidence for patients with AKD is still lacking, several potential pharmacological agents may improve outcomes, including but not limited to angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, mineralocorticoid receptor antagonists, sodium-glucose cotransporter 2 inhibitors, and glucagon-like peptide 1 receptor agonists. In conclusion, accurate prognosis prediction and effective treatment for AKD are critical yet unmet clinical needs. Future studies are urgently needed to improve patient care in this complex and rapidly evolving field.
PubMed: 38934037
DOI: 10.23876/j.krcp.23.289 -
Nutrients Jun 2024Post-traumatic stress disorder (PTSD) is a persistent psychiatric condition that arises following exposure to traumatic events such as warfare, natural disasters, or...
Effects of Evodiamine on Behavior and Hippocampal Neurons through Inhibition of Angiotensin-Converting Enzyme and Modulation of the Renin Angiotensin Pathway in a Mouse Model of Post-Traumatic Stress Disorder.
Post-traumatic stress disorder (PTSD) is a persistent psychiatric condition that arises following exposure to traumatic events such as warfare, natural disasters, or other catastrophic incidents, typically characterized by heightened anxiety, depressive symptoms, and cognitive dysfunction. In this study, animals subjected to single prolonged stress (SPS) were administered evodiamine (EVO) and compared to a positive control group receiving sertraline. The animals were then assessed for alterations in anxiety, depression, and cognitive function. Histological analysis was conducted to examine neuronal changes in the hippocampus. In order to predict the core targets and related mechanisms of evodiamine intervention in PTSD, network pharmacology was used. The metabolic markers pre- and post-drug administration were identified using nontargeted serum metabolomics techniques, and the intersecting Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were screened. Finally, the core targets were validated through molecular docking, enzyme-linked immunosorbent assays, and immunofluorescence staining to confirm the anti-PTSD effects and mechanisms of these targets. As well as improving cognitive impairment, evodiamine reversed anxiety- and depression-like behaviors. It also inhibited the reduction in the number of hippocampal neuronal cells and Nissl bodies in SPS mice inhibited angiotensin converting enzyme (ACE) levels in the hippocampus of SPS mice, and modulated the renin angiotensin pathway and its associated serum metabolites in brain tissue. Evodiamine shows promise as a potential candidate for alleviating the symptoms of post-traumatic stress disorder.
Topics: Animals; Stress Disorders, Post-Traumatic; Hippocampus; Quinazolines; Mice; Neurons; Disease Models, Animal; Male; Renin-Angiotensin System; Behavior, Animal; Angiotensin-Converting Enzyme Inhibitors; Depression; Molecular Docking Simulation; Anxiety; Mice, Inbred C57BL; Network Pharmacology
PubMed: 38931311
DOI: 10.3390/nu16121957 -
Journal of Clinical Medicine Jun 2024: The aim of this study was to examine the association between in-hospital initiation of sodium glucose co-transporter 2 inhibitors (SGLT2is) and outcomes in...
: The aim of this study was to examine the association between in-hospital initiation of sodium glucose co-transporter 2 inhibitors (SGLT2is) and outcomes in hospitalized heart failure (HHF) patients utilizing data from a Greek center. : The present work was a single-center, retrospective, observational study of consecutive HF patients hospitalized in a tertiary center. The study endpoint was all-cause mortality or HF rehospitalization. Univariate and multivariate Cox proportional-hazard models were conducted to investigate the association between SGLT2i administration at discharge and the study endpoint. : Sample consisted of 171 patients, 55 of whom (32.2%) received SGLT2is at discharge. Overall, mean follow-up period was 6.1 months (SD = 4.8 months). Patients who received SGLT2is at discharge had a 43% lower probability of the study endpoint compared to those who did not receive SGLT2is at discharge (HR = 0.57; 95% CI: 0.36-0.91; = 0.018). After adjusting for age, gender, smoking, hemoglobin (Hgb), use of SGLT2is at admission, use of Angiotensin-Converting Enzyme Inhibitors (ACEI-Is)/Angiotensin Receptor Blockers (ARBs) at discharge and Sacubitril/Valsartan at discharge, the aforementioned result remained significant (HR = 0.38; 95% CI: 0.19-0.73; = 0.004). The 55 patients who received SGLT2is at discharge were propensity score matched with the 116 patients who did not receive SGLT2is at discharge. Receiving SGLT2is at discharge continued to be significantly associated with a lower probability of the study endpoint (HR= 0.43; 95% CI: 0.20-0.89; = 0.024). : Initiation of SGLT2is in HHF patients may be associated with better outcomes.
PubMed: 38930091
DOI: 10.3390/jcm13123562 -
International Journal of Molecular... Jun 2024Human infection with the coronavirus disease 2019 (COVID-19) is mediated by the binding of the spike protein of the severe acute respiratory syndrome coronavirus 2...
Human infection with the coronavirus disease 2019 (COVID-19) is mediated by the binding of the spike protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to the human angiotensin-converting enzyme 2 (ACE2). The frequent mutations in the receptor-binding domain (RBD) of the spike protein induced the emergence of variants with increased contagion and can hinder vaccine efficiency. Hence, it is crucial to better understand the binding mechanisms of variant RBDs to human ACE2 and develop efficient methods to characterize this interaction. In this work, we present an approach that uses machine learning to analyze the molecular dynamics simulations of RBD variant trajectories bound to ACE2. Along with the binding free energy calculation, this method was used to characterize the major differences in ACE2-binding capacity of three SARS-CoV-2 RBD variants-namely the original Wuhan strain, Omicron BA.1, and the more recent Omicron BA.5 sublineages. Our analyses assessed the differences in binding free energy and shed light on how it affects the infectious rates of different variants. Furthermore, this approach successfully characterized key binding interactions and could be deployed as an efficient tool to predict different binding inhibitors to pave the way for new preventive and therapeutic strategies.
Topics: Machine Learning; SARS-CoV-2; Angiotensin-Converting Enzyme 2; Humans; Spike Glycoprotein, Coronavirus; Protein Binding; Molecular Dynamics Simulation; COVID-19; Binding Sites; Mutation; Protein Interaction Domains and Motifs
PubMed: 38928241
DOI: 10.3390/ijms25126535