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PloS One 2024Previous experimental and clinical studies suggested a beneficial effect of statins, metformin, angiotensin-converting-enzyme inhibitors and angiotensin II receptor...
BACKGROUND
Previous experimental and clinical studies suggested a beneficial effect of statins, metformin, angiotensin-converting-enzyme inhibitors and angiotensin II receptor blockers (RASi) on portal hypertension. Still, their effects on hard cirrhosis-related clinical endpoints, such as variceal bleeding and bleeding-related mortality, remain to be investigated.
METHODS
Thus, we recorded the use of statins, metformin and RASi in a large cohort of cirrhotic patients undergoing endoscopic band ligation (EBL) for primary (PP, n = 440) and secondary bleeding prophylaxis (SP, n = 480) between 01/2000 and 05/2020. Variceal (re-) bleeding and survival rates were compared between patients with vs. without these co-medications.
RESULTS
A total of 920 cirrhotic patients with varices were included. At first EBL, median MELD was 13 and 515 (56%) patients showed ascites. Statins, metformin and RASi were used by 49 (5.3%), 74 (8%), and 91 (9.9%) patients, respectively. MELD and platelet counts were similar in patients with and without the co-medications of interest. Rates of first variceal bleeding and variceal rebleeding at 2 years were 5.2% and 11.7%, respectively. Neither of the co-medications were associated with decreased first bleeding rates (log-rank tests in PP: statins p = 0.813, metformin p = 0.862, RASi p = 0.919) nor rebleeding rates (log-rank tests in SP: statin p = 0.113, metformin p = 0.348, RASi p = 0.273). Similar mortality rates were documented in patients with and without co-medications for PP (log-rank tests: statins p = 0.630, metformin p = 0.591, RASi p = 0.064) and for SP (statins p = 0.720, metformin p = 0.584, RASi p = 0.118).
CONCLUSION
In clinical practice, variceal bleeding and mortality rates of cirrhotic patients were not reduced by co-medication with statins, metformin or RASi. Nevertheless, we recommend the use of these co-medications by indication, as they may still exert beneficial effects on non-bleeding complications in patients with liver cirrhosis.
Topics: Humans; Metformin; Male; Female; Middle Aged; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Liver Cirrhosis; Gastrointestinal Hemorrhage; Esophageal and Gastric Varices; Aged; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Cohort Studies
PubMed: 38870117
DOI: 10.1371/journal.pone.0302811 -
Heliyon Jun 2024Anti-SARS-CoV-2 and immunomodulatory drugs are important for treating clinically severe patients with respiratory distress symptoms. Alpha- and gamma-mangostins (AM and...
BACKGROUND
Anti-SARS-CoV-2 and immunomodulatory drugs are important for treating clinically severe patients with respiratory distress symptoms. Alpha- and gamma-mangostins (AM and GM) were previously reported as potential 3C-like protease (3CL) and Angiotensin-converting enzyme receptor 2 (ACE2)-binding inhibitors .
OBJECTIVE
We aimed to evaluate two active compounds, AM and GM, from for their antivirals against SARS-CoV-2 in live virus culture systems and their cytotoxicities using standard methods. Also, we aimed to prove whether 3CL and ACE2 neutralization were major targets and explored whether any additional targets existed.
METHODS
We tested the translation and replication efficiencies of SARS-CoV-2 in the presence of AM and GM. Initial and subgenomic translations were evaluated by immunofluorescence of SARS-CoV-2 3CL and N expressions at 16 h after infection. The viral genome was quantified and compared with the untreated group. We also evaluated the efficacies and cytotoxicities of AM and GM against four strains of SARS-CoV-2 (wild-type B, B.1.167.2, B.1.36.16, and B.1.1.529) in Vero E6 cells. The potential targets were evaluated using cell-based anti-attachment, time-of-drug addition, 3CL activities, and ACE2-binding using a surrogated viral neutralization test (sVNT). Moreover, additional targets were explored using combinatorial network-based interactions and Chemical Similarity Ensemble Approach (SEA).
RESULTS
AM and GM reduced SARS-CoV-2 3CL and N expressions, suggesting that initial and subgenomic translations were globally inhibited. AM and GM inhibited all strains of SARS-CoV-2 at EC of 0.70-3.05 μM, in which wild-type B was the most susceptible strain (EC 0.70-0.79 μM). AM was slightly more efficient in the variants (EC 0.88-2.41 μM), resulting in higher selectivity indices (SI 3.65-10.05), compared to the GM (EC 0.94-3.05 μM, SI 1.66-5.40). GM appeared to be more toxic than AM in both Vero E6 and Calu-3 cells. Cell-based anti-attachment and time-of-addition suggested that the potential molecular target could be at the post-infection. 3CL activity and ACE2 binding were interfered with in a dose-dependent manner but were insufficient to be a major target. Combinatorial network-based interaction and chemical similarity ensemble approach (SEA) suggested that fatty acid synthase (FASN), which was critical for SARS-CoV-2 replication, could be a target of AM and GM.
CONCLUSION
AM and GM inhibited SARS-CoV-2 with the highest potency at the wild-type B and the lowest at the B.1.1.529. Multiple targets were expected to integratively inhibit viral replication in cell-based system.
PubMed: 38867992
DOI: 10.1016/j.heliyon.2024.e31987 -
European Heart Journal Supplements :... Apr 2024Arterial hypertension represents the most important cardiovascular risk factor with a direct responsibility for a large share of cardiovascular mortality and morbidity...
Arterial hypertension represents the most important cardiovascular risk factor with a direct responsibility for a large share of cardiovascular mortality and morbidity in the world. Despite the wide availability of antihypertensive therapies with documented effectiveness, blood pressure control still remains largely unsatisfactory in large segments of the population. Guidelines for the management of arterial hypertension suggest the preferential use of five classes of drugs-angiotensin-converting enzyme inhibitors, angiotensin II type I receptor inhibitors, calcium channel blockers, thiazide/thiazide-like diuretics, and beta-blockers-recommending the use of combination therapy, preferably in pre-established combinations, for the majority of hypertensive patients. The evidence of a non-negligible heterogeneity in the response to different antihypertensive drugs in different patients suggests the opportunity for personalization of treatment. The notable phenotypic heterogeneity of the population of hypertensive patients in terms of genetic structure, behavioural aspects, exposure to environmental factors, and disease history imposes the need to consider all the potential determinants of the response to a specific pharmacological treatment. The progressive digitalization of healthcare systems is making enormous quantities of data available for machine learning systems which will allow the development of management algorithms for truly personalized antihypertensive therapy in the near future.
PubMed: 38867857
DOI: 10.1093/eurheartjsupp/suae019 -
Chemical & Pharmaceutical Bulletin Jun 2024In Vietnam, the stems and roots of the Rutaceous plant Paramignya trimera (Oliv.) Burkill (known locally as "Xáo tam phân") are widely used to treat liver diseases...
In Vietnam, the stems and roots of the Rutaceous plant Paramignya trimera (Oliv.) Burkill (known locally as "Xáo tam phân") are widely used to treat liver diseases such as viral hepatitis and acute and chronic cirrhosis. In an effort to search for Vietnamese natural compounds capable of inhibiting coronavirus based on molecular docking screening, two new dimeric coumarin glycosides, namely cis-paratrimerin B (1) and cis-paratrimerin A (2), and two previously identified coumarins, the trans-isomers paratrimerin B (3) and paratrimerin A (4), were isolated from the roots of P. trimera and tested for their anti-angiotensin-converting enzyme 2 (ACE-2) inhibitory properties in vitro. It was discovered that ACE-2 enzyme was inhibited by cis-paratrimerin B (1), cis-paratrimerin A (2), and trans-paratrimerin B (3), with IC values of 28.9, 68, and 77 µM, respectively. Docking simulations revealed that four biscoumarin glycosides had good binding energies (∆G values ranging from -10.6 to -14.7 kcal/mol) and mostly bound to the S1' subsite of the ACE-2 protein. The key interactions of these natural ligands include metal chelation with zinc ions and multiple H-bonds with Ser128, Glu145, His345, Lys363, Thr371, Glu406, and Tyr803. Our findings demonstrated that biscoumarin glycosides from P. trimera roots occur naturally in both cis- and trans-diastereomeric forms. The biscoumarin glycosides Lys363, Thr371, Glu406, and Tyr803. Our findings demonstrated that biscoumarin glycosides from P. trimera roots hold potential for further studies as natural ACE-2 inhibitors for preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.
Topics: Glycosides; Angiotensin-Converting Enzyme 2; Molecular Docking Simulation; Humans; Coumarins; SARS-CoV-2; COVID-19; Rutaceae; COVID-19 Drug Treatment; Antiviral Agents; Plant Roots; Angiotensin-Converting Enzyme Inhibitors
PubMed: 38866495
DOI: 10.1248/cpb.c23-00844 -
Frontiers in Pharmacology 2024Sacubitril-valsartan has been widely reported for reducing the risk of cardiovascular death and improving left ventricular remodeling in patients with heart failure...
Effect of sacubitril-valsartan on left ventricular remodeling in patients with acute myocardial infarction after primary percutaneous coronary intervention: a systematic review and meta-analysis.
BACKGROUND
Sacubitril-valsartan has been widely reported for reducing the risk of cardiovascular death and improving left ventricular remodeling in patients with heart failure (HF). However, the effect of sacubitril-valsartan in patients with acute myocardial infarction (AMI) remains controversial. Therefore, we conducted this meta-analysis to investigate whether sacubitril-valsartan could reverse left ventricular remodeling and reduce cardiovascular adverse events in AMI patients after primary percutaneous coronary intervention (PPCI).
MATERIALS AND METHODS
Two researchers independently retrieved the relevant literature from PubMed, Embase, The Cochrane Library, China National Knowledge Infrastructure (CNKI), and the Wanfang database. The retrieval time was limited from inception to 1 June 2023. Randomized controlled trials (RCTs) meeting the inclusion criteria were included and analyzed.
RESULTS
In total, 21 RCTs involving 2442 AMI patients who underwent PPCI for revascularization were included in this meta-analysis. The meta-analysis showed that compared with the angiotensin-converting enzyme inhibitors (ACEI)/angiotensin receptor blockers (ARB), sacubitril-valsartan treatment in AMI patients after PPCI significantly reduced left ventricular end-diastolic dimension (LVEDD) (weighted mean difference (WMD) -3.11, 95%CI: -4.05∼-2.16, < 0.001), left ventricular end-diastolic volume (LVEDV) (WMD -7.76, 95%CI: -12.24∼-3.27, = 0.001), left ventricular end-systolic volume (LVESV) (WMD -6.80, 95%CI: -9.45∼-4.15, < 0.001) and left ventricular end-systolic dimension (LVESD) (WMD -2.53, 95%CI: -5.30-0.24, < 0.001). Subgroup analysis according to the dose of sacubitril-valsartan yielded a similar result. Meanwhile, PPCI patients using sacubitril-valsartan therapy showed lower risk of major adverse cardiac events (MACE) (OR = 0.36, 95%CI: 0.28-0.46, < 0.001), myocardial reinfarction (OR = 0.54, 95%CI: 0.30-0.98, = 0.041) and HF (OR = 0.35, 95%CI: 0.26-0.47, < 0.001) without increasing the risk of renal insufficiency, hyperkalemia, or symptomatic hypotension. At the same time, the change of LV ejection fraction (LVEF) (WMD 3.91, 95%CI: 3.41-4.41, < 0.001), 6 min walk test (6MWT) (WMD 43.56, 95%CI: 29.37-57.76, < 0.001) and NT-proBNP level (WMD -130.27, 95%CI: -159.14∼-101.40, < 0.001) were statistically significant.
CONCLUSION
In conclusion, our meta-analysis indicates that compared with ACEI/ARB, sacubitril-valsartan may be superior to reverse left ventricular remodeling, improve cardiac function, and effectively reduce the risk of MACE, myocardial reinfarction, and HF in AMI patients after PPCI during follow-up without increasing the risk of adverse reactions including renal insufficiency, hyperkalemia, and symptomatic hypotension.
PubMed: 38863978
DOI: 10.3389/fphar.2024.1366035 -
ESC Heart Failure Jun 2024Sex differences in long-term post-discharge clinical outcomes in Asian patients hospitalized for acute decompensated heart failure (HF) persist despite the world-wide...
AIMS
Sex differences in long-term post-discharge clinical outcomes in Asian patients hospitalized for acute decompensated heart failure (HF) persist despite the world-wide implementation of guideline-directed medical therapy for decades. The present study aims to elucidate the puzzling dilemma and to depict the directions of solution.
METHODS AND RESULTS
Between 2011 and 2020, a total of 12 428 patients (6518 men and 5910 women, mean age 73.50 ± 14.85) hospitalized for acute decompensated HF were retrospectively enrolled from a university HF cohort. Compared with men, women hospitalized for acute decompensated HF were older in age (76.40 ± 13.43 vs. 71.20 ± 15.67 years old, P < 0.0001) with more coexisting hypertension, diabetes, hyperlipidaemia and moderate to severe chronic kidney disease, but less with ischaemic heart disease, cerebrovascular disease and chronic obstructive pulmonary disease (P < 0.0001). In echocardiography measurement parameters, women had smaller left ventricular and left atrial dimensions, higher left ventricular mass index, higher left ventricular ejection fraction (LVEF) and more in HF with preserved ejection fraction (EF) category (LVEF > 50%) than men (P < 0.0001). In HF therapy, women compared with men received more guideline-directed medical HF therapies including angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, angiotensin receptor-neprilysin inhibitors and sodium-glucose cotransporter-2 inhibitors, but similar beta-blockers and mineralocorticoid receptor antagonists (P < 0.0001). Post-discharge long-term clinical outcomes after multivariate-adjusted analysis revealed that women compared with men had lower all-cause mortality [adjusted hazard ratio (aHR): 0.89, 95% confidence interval (CI): 0.84-0.93], lower cardiovascular mortality (aHR: 0.89, 95% CI: 0.80-0.99) and lower 1 year mortality (aHR: 0.91, 95% CI: 0.84-0.99) but similar HF rehospitalization rate (aHR: 1.02, 95% CI: 0.95-1.09) over 8 years of follow-up. The superiority of women over men in all-cause mortality was shown in HF with preserved EF (>50%) and HF with mildly reduced EF (40%-50%), but not in HF with reduced EF (<40%) category. Subgroup forest plot analysis showed body mass index, coexisting hypertension and chronic obstructive pulmonary disease as significant interacting factors.
CONCLUSIONS
With more coronary risk factors and medical comorbidities, less cardiac remodelling and better adherence to guideline-directed HF therapy, women hospitalized for acute decompensated HF demonstrated superiority over men in long-term post-discharge clinical outcomes, including all-cause mortality, cardiovascular mortality and 1 year mortality, and mainly in HF with preserved and mid-range EF categories, in the Asian HF cohort.
PubMed: 38863210
DOI: 10.1002/ehf2.14888 -
Scientific Reports Jun 2024Angiotensin-converting enzyme (ACE) is closely related to cardiometabolic risk factors and atherosclerosis. This study aims to investigate whether the insertion/deletion... (Meta-Analysis)
Meta-Analysis
Angiotensin-converting enzyme (ACE) is closely related to cardiometabolic risk factors and atherosclerosis. This study aims to investigate whether the insertion/deletion (I/D) variant of ACE gene impacts cardiometabolic risk factors, premature coronary artery disease (PCAD), and severity of coronary lesions. PubMed, Cochrane Library, Central, CINAHL, and ClinicalTrials.gov were searched until December 22, 2023. 94,270 individuals were included for the analysis. Carriers of DD genotype had higher levels of triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass index (BMI), and waist circumference (WC) than carriers of II or ID genotypes. In addition, carriers of DD genotype were at high risk of PCAD and multiple vessel lesions. The impacts of ACE I/D variant on lipid levels were significant in American individuals but stronger in male individuals. In contrast, the impacts of ACE I/D variant on PCAD and severity of coronary lesions were primarily significant in Caucasian individuals. This study indicates that the ACE I/D variant has a slight but significant impact on cardiometabolic risk factors, PCAD, and severity of coronary lesions. Angiotensin-converting enzyme inhibitors (ACEI) may benefit high-risk populations with ACE DD genotype to prevent PCAD and multiple vessel lesions.PROSPERO registration number: CRD42023426732.
Topics: Humans; Peptidyl-Dipeptidase A; Coronary Artery Disease; INDEL Mutation; Male; Cardiometabolic Risk Factors; Female; Blood Pressure; Genetic Predisposition to Disease; Severity of Illness Index; Middle Aged; Genotype; Body Mass Index; Risk Factors; Triglycerides; Adult
PubMed: 38849492
DOI: 10.1038/s41598-024-64003-w -
Medecine Tropicale Et Sante... Mar 2024Reducing blood pressure after stroke is important to prevent recurrent stroke, but we have no data about the control of blood pressure in our context. The purpose of...
INTRODUCTION
Reducing blood pressure after stroke is important to prevent recurrent stroke, but we have no data about the control of blood pressure in our context. The purpose of this study was to assess management of hypertension among post-stroke patients in a neurology department.
METHOD
It was a retrospective study involving hypertensive stroke patients. They were followed up at 1, 3, 6 and 12 months after discharge.
RESULTS
141 patients fulfilled the inclusion criteria. The mean age was 61 years. Almost all patients (94.3%) received a dual antihypertensive therapy combining mainly an ACE inhibitor and a diuretic (70.2%). During follow-up, only 76 patients were assessed at M1, 50 at M3, 44 at M6 and 42 at M12. The average monthly cost of antihypertensive treatment was 13,771 CFA francs (21 euros). Non-adherence to antihypertensive medication were mostly noted in widows, patients without occupation, those with low education and no health insurance. At one year, blood pressure was controlled in 80% of the 42 patients still present. Non-control of blood pressure was related to poor therapeutic compliance (p<0.05).
CONCLUSION
This study highlights follow-up issues in hypertensive post-stroke patients with a high number of lost to follow-up. Blood pressure was controlled in patients who were regularly followed and adherent to antihypertensive treatment.
Topics: Humans; Hypertension; Female; Male; Middle Aged; Stroke; Cote d'Ivoire; Retrospective Studies; Antihypertensive Agents; Aged; Neurology; Hospital Departments; Medication Adherence; Follow-Up Studies
PubMed: 38846129
DOI: 10.48327/mtsi.v4i1.2024.366 -
Journal of the American Heart... Jun 2024The effect of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARBs) on major adverse cardiovascular events (MACE) in patients who undergo...
BACKGROUND
The effect of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARBs) on major adverse cardiovascular events (MACE) in patients who undergo coronary artery bypass graft surgery is equivocal. This retrospective, population-based cohort study evaluated effect of exposure to an ACEI/ARB on MACE using linked administrative databases that included all cardiac revascularization procedures, hospitalizations, and prescriptions for the population of British Columbia, Canada.
METHODS AND RESULTS
All adults who underwent coronary artery bypass graft surgery between 2002 and 2020 were eligible. The primary outcome was time to MACE, defined as a composite of all-cause death, myocardial infarction, and ischemic stroke using Cox proportional hazards models with inverse probability treatment weighting. Included were 15 439 patients and 6191 (40%) were prescribed an ACEI/ARB. Mean age was 66 years, 83% were men, and 16% had heart failure (HF). Median exposure time was 40 months. Over the 5-year follow-up, 1623 MACE occurred. Impact of exposure was different for patients with and without HF ( <0.0001 for interaction). After probability-weighting and adjustment for relevant covariates, exposure to ACEI/ARBs was associated with a lower hazard of MACE in patients with HF at 1 year (hazard ratio, 0.13 [95% CI, 0.09-0.19]) and 5 years (hazard ratio, 0.36 [95% CI, 0.30-0.44]). In patients without HF, ACEI/ARBs had a lower hazard of MACE at 1 year (hazard ratio, 0.35 [95% CI, 0.27-0.46]) and 5 years (hazard ratio, 0.66 [95% CI, 0.58-0.76]).
CONCLUSIONS
In this population-based study, ACEI/ARBs were associated with a lower hazard of MACE in a cohort of patients post-coronary artery bypass graft surgery irrespective of HF status.
Topics: Humans; Coronary Artery Bypass; Angiotensin-Converting Enzyme Inhibitors; Male; Female; Aged; Angiotensin Receptor Antagonists; Retrospective Studies; British Columbia; Middle Aged; Coronary Artery Disease; Treatment Outcome; Risk Factors; Myocardial Infarction; Time Factors; Postoperative Complications
PubMed: 38842283
DOI: 10.1161/JAHA.124.035215 -
Renal Failure Dec 2024To determine the efficacy and safety of Astragalus combined with renin-angiotensin-aldosterone system (RAAS) blockers in treating stage III diabetic nephropathy (DN) by... (Meta-Analysis)
Meta-Analysis
Efficacy of astragalus combined with renin-angiotensin-aldosterone system blockers in the treatment of stage III diabetic nephropathy: a systematic review and meta-analysis.
OBJECTIVE
To determine the efficacy and safety of Astragalus combined with renin-angiotensin-aldosterone system (RAAS) blockers in treating stage III diabetic nephropathy (DN) by meta-analysis.
METHODS
PubMed, Embase, Cochrane Library, Wiley, and Web of Science databases were searched for articles published between August 2007 and August 2022. Clinical studies on Astragalus combined with RAAS blockers for the treatment of stage III DN were included. Meta-analysis was performed by RevMan 5.1 and Stata 14.3 software.
RESULTS
A total of 32 papers were included in this meta-analysis, containing 2462 patients from randomized controlled trials, with 1244 receiving the combination treatment and 1218 solely receiving RAAS blockers. Astragalus combined with RAAS blockers yielded a significantly higher total effective rate (TER) (mean difference [MD] 3.63, 95% confidence interval [CI] 2.59-5.09) and significantly reduced urinary protein excretion rate (UPER), serum creatinine (Scr), blood urine nitrogen (BUN) and glycosylated hemoglobin (HbAlc) levels. In subgroup analysis, combining astragalus and angiotensin receptor blocker significantly lowered fasting plasma glucose (FPG) and 24 h urinary protein (24hUTP) levels, compared with the combined astragalus and angiotensin-converting enzyme inhibitor treatment. Meanwhile, the latter significantly decreased the urinary microprotein (β-MG). Importantly, the sensitivity analysis confirmed the study's stability, and publication bias was not detected for UPER, BUN, HbAlc, FPG, or β-MG. However, the TER, SCr, and 24hUTP results suggested possible publication bias.
CONCLUSIONS
The astragalus-RAAS blocker combination treatment is safe and improves outcomes; however, rigorous randomized, large-scale, multi-center, double-blind trials are needed to evaluate its efficacy and safety in stage III DN.
Topics: Humans; Diabetic Nephropathies; Angiotensin-Converting Enzyme Inhibitors; Renin-Angiotensin System; Drug Therapy, Combination; Angiotensin Receptor Antagonists; Astragalus Plant; Randomized Controlled Trials as Topic; Drugs, Chinese Herbal; Treatment Outcome; Creatinine; Glycated Hemoglobin; Proteinuria
PubMed: 38836372
DOI: 10.1080/0886022X.2024.2359033