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Paul SK, Guendouzi A, Banerjee A, Guendouzi A, Haldar R. Identification of approved drugs with ALDH1A1 inhibitory potential aimed at enhancing chemotherapy sensitivity in cancer cells: an in-silico drug repurposing approach. J Biomol Struct Dyn 2025; 43:3830-3844. [PMID: 38189344 DOI: 10.1080/07391102.2023.2300127] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2023] [Accepted: 12/21/2023] [Indexed: 01/09/2024]
Abstract
The aldehyde dehydrogenase 1A1 (ALDH1A1) also known as retinal dehydrogenase, is an enzyme normally involved in the cellular metabolism, development and detoxification processes in healthy cells. However, it's also considered a cancer stem cell marker and its high levels of expression in several cancers, including breast, lung, ovarian, and colon cancer have been associated with poor prognosis and resistance to chemotherapy. Given its crucial role in chemotherapy resistance by detoxification of chemotherapeutic drugs, ALDH1A1 has attracted significant research interest as a potential therapeutic target for cancer. Though a few synthetic inhibitors of ALDH1A1 have been synthesized and their efficacy has been proved in-vitro and in-vivo studies, none of them have passed clinical trials so far. In this scenario, we have performed an in-silico study to verify whether any of the already approved drugs used for various purposes has the ability to inhibit catalytic activity of ALDH1A1, so that they can be repurposed for cancer therapy. Keeping in mind the feasibility of repurposing in a larger population we have selected the approved drugs from five widely used drug categories such as antibiotic, antiviral, antifungal, anti diabetic and antihypertensive for screening. Computational techniques like molecular docking, molecular dynamics simulations and MM-PBSA binding energy calculation have been used in this study to screen the approved drugs. Based on the logical analysis of results, we propose that three drugs - telmisartan, irbesartan and maraviroc can inhibit the catalytic activity of ALDH1A1 and thus can be repurposed to increase chemotherapy sensitivity in cancer cells.
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Affiliation(s)
- Sanjay Kumar Paul
- Department of Physiology, University of Calcutta, Kolkata, India
- Department of Zoology, Rammohan College, Kolkata, West Bengal, India
| | - Abdelmadjid Guendouzi
- Center for Research in Pharmaceutical Sciences (CRSP), Constantine, Algeria
- Ecole Normale Supérieure ENS Constantine, Constantine, Algeria
| | | | | | - Rajen Haldar
- Department of Physiology, University of Calcutta, Kolkata, India
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Alhawari H, Jarrar Y, Zihlif M, Wahbeh A, Alshelleh S, Ojjoh K, Abdelrazaq D, Alhawari H. Variability in Response to Valsartan and Its Relationship With AGT M235T Genotype and Other Nongenetic Parameters Among a Sample of Hypertensive Individuals in Jordan: A Prospective Pilot Study. Health Sci Rep 2025; 8:e70611. [PMID: 40248396 PMCID: PMC12003916 DOI: 10.1002/hsr2.70611] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2024] [Revised: 02/23/2025] [Accepted: 03/11/2025] [Indexed: 04/19/2025] Open
Abstract
Background Valsartan, an angiotensin receptor antagonist widely used in hypertension and heart failure management, exhibits noticeable interindividual variation in response among hypertensive patients at the University of Jordan Hospital. The angiotensinogen (AGT) gene variant M235T, a functional genetic variant, influences the renin-angiotensin system. Aims This study aims to explore interindividual variations in the valsartan response, considering genetics, particularly the AGT M235T variant, and other nongenetic factors. Methods This cohort study involved 95 unrelated Arabic Jordanians diagnosed with essential hypertension. Systolic (SBP) and diastolic blood pressure (DBP) measurements were taken at the initiation of 160 mg valsartan and after 1 month of treatment, assessing the valsartan response for each patient. Genetic analysis of AGT M235T was done using the polymerase chain reaction-restriction fragment length polymorphism genotyping method. Anthropometric data were collected from University of Jordan Hospital computer records. Results Valsartan response assessment revealed diverse individual responses, the response to valsartan varied, with SBP reductions from < 10 to > 70 mmHg and DBP from < 2 to 30 mmHg. Patients with homozygous AGT M235T genotypes showed a less significant response (p < 0.05) to valsartan than heterozygous and reference genotypes. Additionally, results indicated a positive correlation of age (p = 0.03) and a negative correlation of height (p = 0.02-0.04) with the valsartan response. Regression analysis demonstrated that the patients' sex significantly influenced the valsartan response (p < 0.05). Conclusions This study identifies the AGT M235T genotype as a potential genetic contributor to variability in the valsartan response. Associations with age, height, and sex underscore the importance of considering genetic and demographic factors in tailoring valsartan therapy, for advancing personalized hypertension management.
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Affiliation(s)
- Hussein Alhawari
- Department of Internal MedicineSchool of Medicine, The University of JordanAmmanJordan
| | - Yazun Jarrar
- Department of Basic Medical SciencesFaculty of Medicine, Al‐Balqa Applied UniversityAl‐SaltJordan
| | - Malek Zihlif
- Department of PharmacologySchool of Medicine, The University of JordanAmmanJordan
| | - Ayman Wahbeh
- Department of Internal MedicineSchool of Medicine, The University of JordanAmmanJordan
| | - Sameeha Alshelleh
- Department of Internal MedicineSchool of Medicine, The University of JordanAmmanJordan
| | - Khaled Ojjoh
- Department of Internal MedicineSchool of Medicine, The University of JordanAmmanJordan
| | - Dalia Abdelrazaq
- Department of PharmacologySchool of Medicine, The University of JordanAmmanJordan
| | - Hussam Alhawari
- Department of Internal MedicineSchool of Medicine, The University of JordanAmmanJordan
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Ogura T, Shiraishi C. Comparison of Adverse Events Among Angiotensin Receptor Blockers in Hypertension Using the United States Food and Drug Administration Adverse Event Reporting System. Cureus 2025; 17:e81912. [PMID: 40342468 PMCID: PMC12061515 DOI: 10.7759/cureus.81912] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/08/2025] [Indexed: 05/11/2025] Open
Abstract
Background Angiotensin receptor blockers (ARBs) are pivotal in hypertension management. Despite sharing a common mechanism of blocking angiotensin II receptors, ARBs exhibit varying pharmacokinetic and pharmacodynamic properties that influence safety profiles. ARBs have been linked to adverse events (AEs) across multiple organ systems, including skin (e.g., angioedema), neurological (e.g., dizziness), and cardiovascular disorders (e.g., hypotension). Understanding these differences is essential for optimizing clinical decision-making. Objectives This study compared AE profiles of seven ARBs in patients with hypertension using data from the United States Food and Drug Administration Adverse Event Reporting System (FAERS). To enhance result reliability and control for confounding factors, only cases where ARBs were explicitly indicated for hypertension treatment were included. FAERS is a valuable post-marketing surveillance tool that captures spontaneous AE reports, although it has limitations such as reporting bias. The findings aim to generate hypotheses regarding ARB-associated AEs for future research using robust study designs. Methods A retrospective analysis of FAERS data between 2004 and 2024 was conducted. Patients prescribed ARBs for hypertension were included, while those with missing prescription indications or alternative uses were excluded. Reporting odds ratio (ROR) and adjusted ROR (aROR) were calculated to compare reporting proportions (RPs) among ARBs, with each ARB sequentially used as the reference in pairwise comparisons. The Bonferroni correction addressed multiple comparisons, with an adjusted significance level of 0.05/21=0.0024. For aROR calculations, cases with unknown values in adjustment variables were excluded. To enhance robustness, results were considered significant only when both ROR and aROR showed significance. Results Using losartan as the reference, valsartan, irbesartan, candesartan, telmisartan, and olmesartan demonstrated significantly lower RPs for skin disorders. For instance, the RP for skin disorders was 10.6 for losartan compared to 6.1 for valsartan (ROR: 0.545, p<0.0001; aROR: 0.648, p<0.0001) and 4.2 for olmesartan (ROR: 0.368, p<0.0001; aROR: 0.412, p<0.0001). Conversely, valsartan and olmesartan exhibited significantly higher RPs for cardiovascular disorders, with 23.7 for valsartan (ROR: 1.574, p<0.0001; aROR: 1.570, p<0.0001) and 19.0 for olmesartan (ROR: 1.186, p<0.0001; aROR: 1.278, p<0.0001) compared to 16.5 for losartan. Similar trends were observed when other ARBs were used as references, revealing a heterogeneous distribution of AE profiles among the seven ARBs. Conclusions This study reveals distinct AE patterns among ARBs in hypertension management. No single ARB exhibited universally favorable safety profiles across all AE categories, emphasizing the need for personalized prescribing. When selecting an ARB, prescribers should consider patient-specific risk factors and comorbidities. For instance, patients with a history of skin disorders may benefit from ARBs other than losartan. Conversely, patients with elevated cardiovascular risk may require closer monitoring when prescribed valsartan, including more frequent follow-up visits or additional cardiovascular diagnostics to detect early AEs. These findings enable healthcare providers to tailor ARB selection and monitoring strategies to optimize efficacy and safety in hypertension treatment.
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Affiliation(s)
- Toru Ogura
- Department of Biostatistics, Clinical Research Support Center, Mie University Hospital, Tsu, JPN
| | - Chihiro Shiraishi
- Department of Emergency and Disaster Medical Pharmacy, Fukuoka University, Fukuoka, JPN
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Farrera DO, Alaaldin MM, Lindberg P, Sample PA, Lenzen-Hammerel P, LaMadrid CS, Haymore R, Wright SH, Cherrington NJ. Alterations of valsartan pharmacokinetics in a rodent model of metabolic dysfunction-associated steatohepatitis. Drug Metab Dispos 2025; 53:100043. [PMID: 40054126 DOI: 10.1016/j.dmd.2025.100043] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2024] [Accepted: 01/21/2025] [Indexed: 03/30/2025] Open
Abstract
Valsartan (VAL) is commonly prescribed for patients with cardiovascular disease (CVD) to lower blood pressure, reduce heart failure risk, and prevent heart attacks or strokes by blocking the effects of angiotensin II. Many patients with CVD also suffer from metabolic dysfunction-associated steatohepatitis (MASH), which disrupts several xenobiotic transporters, affecting the pharmacokinetics of numerous drugs. Medications used in patients to treat comorbidities associated with MASH may be subject to this altered disposition and potential toxicity. This study aimed to assess how MASH alters the pharmacokinetics of VAL using a rodent model that mimics human MASH. MASH was induced in rats via a methionine- and choline-deficient (MCD) diet. Rats received VAL-a substrate of organic anion-transporting polypeptide (OATP) 1B1/1B3 and reported for multidrug resistance-associated protein-2-(2 mg/kg) through intravenous injection to isolate hepatic transport processes, and bile, serum, and liver concentrations measured using liquid chromatography-tandem mass spectrometry. Consistent with MASH progression, MCD rats presented with more gross pathology, including increased liver-to-body weight ratios, along with macrosteatosis, hepatocyte ballooning, and lobular inflammation. In MCD rats, the expression of Oatp1b2 was significantly reduced, and Mrp2 was internalized, resulting in higher systemic exposure to VAL compared with controls. Additionally, cumulative biliary excretion of VAL was lower in MCD rats. To further assess VAL disposition in MASH, transport kinetics were evaluated in human embryonic kidney 293 cells overexpressing OATP1B1 or OATP1B3, revealing similar affinity for VAL between both transporters. These findings suggest that changes in OATP function in MASH may alter VAL pharmacokinetics, which may have implications for personalized treatments. SIGNIFICANCE STATEMENT: Although expression of drug transporters in metabolic dysfunction-associated steatohepatitis (MASH) has been explored, the combined effect between MASH and genetic loss of transporters on the disposition of sartan drugs has not been determined. This study applied liquid chromatography-tandem mass spectrometry analyses and immunohistological staining to assess drug disposition and identify alterations to drug transporters in rodents on a methionine- and choline-deficient diet. The observations made in this study have significant implications regarding its disposition in the context of hepatic dysfunction associated with MASH.
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Affiliation(s)
- Dominique O Farrera
- College of Pharmacy, Department of Pharmacology & Toxicology, The University of Arizona, Tucson, Arizona
| | - Mina M Alaaldin
- College of Pharmacy, Department of Pharmacology & Toxicology, The University of Arizona, Tucson, Arizona
| | - Paige Lindberg
- College of Pharmacy, Department of Pharmacology & Toxicology, The University of Arizona, Tucson, Arizona
| | - Paxton A Sample
- College of Pharmacy, Department of Pharmacology & Toxicology, The University of Arizona, Tucson, Arizona
| | - Paige Lenzen-Hammerel
- College of Pharmacy, Department of Pharmacology & Toxicology, The University of Arizona, Tucson, Arizona
| | - Christopher S LaMadrid
- College of Pharmacy, Department of Pharmacology & Toxicology, The University of Arizona, Tucson, Arizona
| | - Ryan Haymore
- College of Pharmacy, Department of Pharmacology & Toxicology, The University of Arizona, Tucson, Arizona
| | - Stephen H Wright
- College of Medicine, Department of Physiology, The University of Arizona, Tucson, Arizona
| | - Nathan J Cherrington
- College of Pharmacy, Department of Pharmacology & Toxicology, The University of Arizona, Tucson, Arizona.
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Patil N, Patil VS, Punase N, Mapare G, Bhatt S, Patil CR. Comparative Efficacy of β-Carotene and Losartan Against Isoproterenol-Induced Cardiac Fibrosis: An Experimental and Computational Studies. JOURNAL OF THE AMERICAN NUTRITION ASSOCIATION 2025:1-16. [PMID: 39927680 DOI: 10.1080/27697061.2025.2461217] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/25/2024] [Revised: 01/05/2025] [Accepted: 01/28/2025] [Indexed: 02/11/2025]
Abstract
OBJECTIVE β-carotene, a vitamin A precursor is reported to inhibit molecular pathways cardinal to pathogenesis of fibrotic tissue alterations and in this study, the effectiveness of 14 days oral administration of β-carotene (10, 20, and 40 mg/kg/day) in the cardiac fibrosis (CF) in rats was studied and explored the mechanisms through network pharmacology. METHODS CF was induced by isoproterenol (ISO) 6 mg/kg/SC from day 1 to day 7. Losartan (LOS) 10 mg/kg/day/p.o. served as the standard. Both β-carotene and LOS were administered from day 1 to 14. On the 15th day, ECG and blood pressure (systolic, diastolic and mean) were recorded in the anesthetized rats followed by their euthanasia. The extent of cardiac fibrosis in the isolated hearts was determined using heart coefficient, tissue levels of hydroxyproline, histological examination. The oxidative stress in cardiac tissue was estimated, as GSH, SOD, catalase, MDA and NO. β-carotene targeted proteins pathway, process, and functional enrichment analysis were explored through network pharmacology. RESULTS β-carotene dose-dependently mitigated the biochemical and histological changes induced by ISO in heart tissues. In ECG, it restored ST height, QT, and QRS intervals. Additionally, it normalized systolic, diastolic, and mean arterial pressures. The reduction in heart coefficient suggests β-carotene's potential to inhibit collagen deposition in heart tissue. β-carotene normalized oxidative stress markers, and hydroxyproline levels. All other biochemical parameters were restored to normal levels with β-carotene treatment. β-carotene 40 mg/kg dose showed comparable effect to that of LOS 10 mg/kg. β-carotene modulated IL-17, TNF, NF-kappa B, HIF-1, Sphingolipid, Relaxin, Adipocytokine, cAMP, Toll-like receptor, MAPK, PI3K-Akt, cGMP-PKG, VEGF, Ras, and PPAR signaling pathways. CONCLUSIONS β-carotene dose-dependently protects against ISO-induced CF in rats, with 40 mg/kg as an effective antifibrotic dose.
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Affiliation(s)
- Niharika Patil
- Department of Pharmacology, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur, Maharashtra, India
| | - Vishal S Patil
- Department of Pharmacology, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur, Maharashtra, India
| | - Nandeeni Punase
- Department of Pharmacology, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur, Maharashtra, India
| | - Ghanshyam Mapare
- Department of Pharmacology, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur, Maharashtra, India
| | - Shvetank Bhatt
- School of Health Sciences and Technology, Vishwanath Karad MIT World Peace University, Kothrud, Pune, India
| | - Chandragouda R Patil
- Department of Pharmacology, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur, Maharashtra, India
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Wang J, Zhao Y, Chen Z, Huang R. Safety of combined drug use in patients with cardiovascular and cerebrovascular diseases: an analysis based on the spontaneous reporting database of adverse drug reactions in Hubei Province. Front Pharmacol 2025; 15:1451713. [PMID: 39845792 PMCID: PMC11751046 DOI: 10.3389/fphar.2024.1451713] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2024] [Accepted: 12/23/2024] [Indexed: 01/24/2025] Open
Abstract
Objective There is a lack of studies investigating the safety of combination regimens specifically for cardiovascular and cerebrovascular diseases. This study aimed to evaluate the safety of combination drugs for cardiovascular and cerebrovascular diseases using real-world data. Methods We analyzed adverse drug reaction data received by the Hubei Adverse Drug Reaction Center from the first quarter of 2014 to the fourth quarter of 2022. The safety of combined drugs for cardiovascular and cerebrovascular diseases in different people was assessed using the association rule method and Ω shrinkage measurement. Results A total of 53,038 reports were included in this study, revealing 9 signals of adverse reactions caused by combination drugs. The strongest signal found in this study was jaundice caused by the combination of amlodipine and atorvastatin (Ω 0.025:3.08, lift: 1116.69, conviction: 1.75). Additionally, the combination of aspirin with other drugs was associated with hemorrhaging in various organs. Female patients showed a cold signal when taking vitamin C and vitamin B6 together compared to male patients (Ω 0.025:0.89, lift: 7.15, conviction: 1.12). Patients under 60 years old had a palpitations signal when combining eritrea bei sha Tanzania and felodipine (Ω 0.025:0.41, lift: 14.65, conviction: 3.8), and an erythema signal when combining nifedipine (Ω 0.025:0.23, lift: 8.17, conviction: 1.077). Conclusion Among the 9 signals identified in this study, 4 were off-label adverse drug reactions that require further clinical research for exploration and confirmation, in order to provide more scientifically informed drug labeling. Five adverse events associated with aspirin-induced bleeding were identified. Notably, different adverse drug reactions were observed in different populations, suggesting the need for future studies to expedite the development of personalized medicine.
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Affiliation(s)
- Jia Wang
- Personnel section, Traditional Chinese and Western Medicine Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yuhang Zhao
- School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Zherui Chen
- School of Statistics and Mathematics, Zhongnan University of Economics and Law, Wuhan, China
| | - Rui Huang
- School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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O'Hara DV, Bassi A, Wilcox A, Jha V, Rathore V, D'Cruz S, Snelling TL, Jones M, Totterdell J, Bangi A, Jain MK, Pollock C, Burrell L, Fox G, Jones C, Kotwal S, Faridah Syed Omar S, Jardine M. Combination of the chemokine receptor type 2 (CCR2) antagonist DMX-200 and candesartan for COVID-19: a randomised controlled trial. BMJ Open 2024; 14:e081790. [PMID: 39438096 PMCID: PMC11499840 DOI: 10.1136/bmjopen-2023-081790] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2023] [Accepted: 09/17/2024] [Indexed: 10/25/2024] Open
Abstract
OBJECTIVE To determine whether a chemokine receptor type 2 antagonist, DMX-200 (repagermanium), in combination with an angiotensin receptor blocker, candesartan, improves clinical outcomes in people with COVID-19. DESIGN Prospective, multicentre, double-blind, placebo-controlled trial. SETTING Ten acute care hospitals in India. PARTICIPANTS Adults <65 years old intended for hospital admission with moderate/severe COVID-19 disease (respiratory rate ≥24 breaths per minute or oxygen saturation ≤93% on room air). INTERVENTION DMX-200 120 mg two times per day, or placebo, on background of titratable candesartan commencing at 4 mg two times per day, for 28 days. MAIN OUTCOME MEASURES The primary endpoint was COVID-19 disease severity on a modified WHO Clinical Progression Scale (WHO scale) on day 14. Secondary outcomes included the WHO scale at days 28, 60, 90 and 180; intensive care unit (ICU) admission, respiratory failure or death within 28 days; length of hospitalisation; and requirement for ventilatory support or dialysis. RESULTS Between December 2021 and August 2022, 518 people were screened, with 49 randomised to DMX-200 or placebo on a background of candesartan. The study was terminated early due to recruitment barriers, including an external requirement to restrict enrolment to adults <65 years old, contributing to a 91% screen failure rate. The median WHO Clinical Progression Scale (WHO scale) score at day 14 for both groups was 1 (IQR 1-1), indicating most participants were discharged with no limitations on activities by this time. Formal comparison was not performed due to the small sample size. One participant receiving DMX-200 died of COVID-19 disease progression. No participants required ICU admission, ventilation or dialysis. Median length of hospitalisation in both groups was 6 days (IQR 6-7 days). WHO scale scores were similar at 28, 60, 90 and 180 days. CONCLUSION Due to recruitment barriers, the study was unable to determine whether DMX-200 improves clinical outcomes in people with COVID-19. TRIAL REGISTRATION NUMBER ClinicalTrials.gov NCT05122182.
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Affiliation(s)
- Daniel Vincent O'Hara
- NHMRC Clinical Trials Centre, Camperdown, New South Wales, Australia
- Department of Renal Medicine, Royal North Shore Hospital, St Leonards, New South Wales, Australia
| | - Abhinav Bassi
- The George Institute for Global Health India, New Delhi, Delhi, India
| | - Arlen Wilcox
- NHMRC Clinical Trials Centre, Camperdown, New South Wales, Australia
| | - Vivekanand Jha
- The George Institute for Global Health India, New Delhi, Delhi, India
- Prasanna School of Public Health, Manipal Academy of Higher Education, Manipal, India
- School of Public Health, Imperial College, London, UK
| | - Vinay Rathore
- All India Institute of Medical Sciences, Raipur, India
| | - Sanjay D'Cruz
- Government Medical College and Hospital, Chandigarh, India
| | - Thomas L Snelling
- NHMRC Clinical Trials Centre, Camperdown, New South Wales, Australia
| | - Mark Jones
- NHMRC Clinical Trials Centre, Camperdown, New South Wales, Australia
| | - James Totterdell
- School of Public Health, The University of Sydney, Camperdown, New South Wales, Australia
| | | | | | - Carol Pollock
- Department of Renal Medicine, Royal North Shore Hospital, St Leonards, New South Wales, Australia
- Kolling Institute of Medical Research, St Leonards, New South Wales, Australia
- Sydney Medical School, The University of Sydney, Camperdown, New South Wales, Australia
| | - Louise Burrell
- Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia
- Institute for Breathing and Sleep, Heidelberg, Victoria, Australia
| | - Gregory Fox
- Central Clinical School, The University of Sydney, Camperdown, New South Wales, Australia
- Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia
| | - Cheryl Jones
- Sydney Medical School, The University of Sydney, Camperdown, New South Wales, Australia
| | - Sradha Kotwal
- Renal and Metabolic Division, George Institute for Global Health, Sydney, New South Wales, Australia
- Prince of Wales Hospital and Community Health Services, Randwick, New South Wales, Australia
| | | | - Meg Jardine
- NHMRC Clinical Trials Centre, Camperdown, New South Wales, Australia
- Concord Repatriation General Hospital, Concord, New South Wales, Australia
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Escobar C, Mazón P, Rivadulla C, Chandrappa S. The role of eprosartan in the management of essential hypertension: literature review and expert opinion. Expert Rev Cardiovasc Ther 2024; 22:575-587. [PMID: 39435482 DOI: 10.1080/14779072.2024.2418298] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2023] [Revised: 09/09/2024] [Accepted: 10/15/2024] [Indexed: 10/23/2024]
Abstract
INTRODUCTION Eprosartan is an angiotensin receptor blocker (ARB) used for management of essential hypertension. With unique pharmacological characteristics, dual action mechanism, and clinical effectiveness, eprosartan offers additional advantages over other ARBs in specific patient populations. AREAS COVERED A comprehensive review of the literature was performed across publicly available databases, with no time limitations, to ensure the inclusion of all relevant studies. The review focuses on presenting the efficacy and safety profile of eprosartan, alone or in combination with other agents. Additionally, it explores the etiology of hypertension concerning the structure and function of angiotensin II type 1 receptors. Further, the efficacy of eprosartan in special populations and its additional benefits are also discussed. EXPERT OPINION Eprosartan effectively reduces blood pressure (BP), with a 24-hour BP-lowering effect at 600 mg/day. Eprosartan demonstrates similar or better efficacy than other ARBs, such as telmisartan and losartan, particularly in managing coagulation-related abnormalities and peripheral resistance. In combination therapy, eprosartan with hydrochlorothiazide significantly enhances BP reduction. Eprosartan is well-tolerated, with a low incidence of adverse events, making it a reliable choice for long-term hypertension management across various patient populations, such as those with comorbid diabetes and renal disease and older adults.
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Affiliation(s)
- Carlos Escobar
- Cardiology Department, University Hospital La Paz, Madrid, Spain
| | - Pilar Mazón
- Cardiology Department, University Hospital, Santiago de Compostela, Spain
- Centro de Investigación Biomédica en Red - Enfermedades Cardiovasculares (CIBERCV), Spain
| | - Claudio Rivadulla
- Cardiology Department, 12 de Octubre University Hospital, Madrid, Spain
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Lee H, Park CS, Kim B, Rhee TM, Lee H, Kim YJ, Han K, Kim HK. Real-world efficacy of fimasartan vs. other angiotensin receptor blockers in combination with calcium channel blockers: a nationwide cohort study. Clin Hypertens 2024; 30:28. [PMID: 39350304 PMCID: PMC11443630 DOI: 10.1186/s40885-024-00287-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2024] [Accepted: 09/13/2024] [Indexed: 10/04/2024] Open
Abstract
BACKGROUND The antihypertensive efficacy of fimasartan was assessed based on the transition rate from a combination of calcium channel blockers (CCB) and angiotensin receptor blockers (ARB) to three-drug combination therapy, as compared to other ARBs. METHODS This nationwide cohort study used data obtained from the Korean National Health Insurance Service database. Patients who had received national health checkups within 2 years prior to January 1, 2017, and were concurrently prescribed ARBs and CCBs for > 30 days during the 6 months from January 1, 2017, to June 30, 2017 were included in the study. Patients were categorized into the 'fimasartan group' (those prescribed fimasartan) and the 'non-fimasartan group' (those prescribed ARBs other than fimasartan). The index date was set as the last day of a 30-day prescription period for ARBs and CCBs, with a subsequent 2.5-year follow-up to observe the potential addition of a third drug, such as beta-blockers or diuretics. RESULTS The study included 34,422 patients with a mean age of 60.3 years and 58.3% being male. The fimasartan group constituted 2.7% (n = 928) of the total, and the non-fimasartan group, 97.3% (n = 33,494). During the follow-up period, 38 patients in the fimasartan group (14.3 per 1,000 person-years) and 3,557 patients in the non-fimasartan group (42.8 per 1,000 person-years) required additional antihypertensive medications. After multivariate adjustment for age, sex, diabetes mellitus, dyslipidemia, cancer, heart failure, systolic blood pressure, and diastolic blood pressure, the fimasartan group showed a significantly lower rate of adding a third medication (hazard ratio 2.68, 95% confidence interval 1.95-3.69) compared to that of the non-fimasartan group. CONCLUSIONS Fimasartan is associated with a lower need for additional antihypertensive drugs compared to other ARBs. This implies its greater effectiveness in hypertension management, potentially enhancing cardiovascular outcomes, and minimizing polypharmacy.
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Affiliation(s)
- Huijin Lee
- Department of Critical Care Medicine, Seoul National University Hospital, Seoul, Republic of Korea
| | - Chan Soon Park
- Division of Cardiology, Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea
| | - Bongseong Kim
- Department of Statistics and Actuarial Science, Soongsil University, Seoul, Republic of Korea
| | - Tae-Min Rhee
- Division of Cardiology, Department of Internal Medicine, Seoul National University Hospital Healthcare System Gangnam Center, 152, Teheran-ro, Gangnam-gu, Seoul, Republic of Korea
| | - Heesun Lee
- Division of Cardiology, Department of Internal Medicine, Seoul National University Hospital Healthcare System Gangnam Center, 152, Teheran-ro, Gangnam-gu, Seoul, Republic of Korea
| | - Yong-Jin Kim
- Division of Cardiology, Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Kyungdo Han
- Department of Statistics and Actuarial Science, Soongsil University, Seoul, Republic of Korea
| | - Hyung-Kwan Kim
- Division of Cardiology, Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea.
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
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10
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Richardson JD, Kline HL, Ko BY, Hooper A, Komanapalli S, Alvarez-Del-Pino JD, Yeh E. Addressing Health Disparities in Hypertension: A Comprehensive Medical Elective and Survey Study Among Medical Students and Professionals. MEDICAL SCIENCE EDUCATOR 2024; 34:1107-1115. [PMID: 39450033 PMCID: PMC11496450 DOI: 10.1007/s40670-024-02099-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 06/05/2024] [Indexed: 10/26/2024]
Abstract
Introduction Medical education utilizes standard clinical practice and recommends clinical algorithms to inform trainee curricula. The use of race and ethnicity as a medical screening tool impacts medical outcomes by associating race with genetics without considering that race incorporates social, economic, and cultural variables that influence outcomes. Methods To evaluate underlying factors contributing to differences in hypertension prevalence, control, and treatment recommendations across race/ethnicities, a 2-week elective course was developed for third- and fourth-year medical students. In this elective course, students performed self-directed literature-based research on hypertension health disparities. We then developed three videos that addressed the racial/ethnic impact on hypertension prevalence and control and incorporated the students' research findings. The videos were presented at a lunch-and-learn session, open to medical students and health professionals, that was focused on healthcare inequities in hypertension. Pre- and post-session survey data was collected to assess how the discussion changed participant knowledge and impressions of the role race plays in hypertension prevalence, control, and treatment. Results Survey results denoted that 100% of lunch-and-learn participants increased their understanding of the impact of health inequities on hypertension. Overall, there were significant differences in knowledge gained and understanding of health disparities that influence hypertension treatment across participants from all genders and racial or ethnic groups. Notably, pre-session survey results indicated that participants tended to agree that treatment guidelines incorporating race improve equity in the treatment of hypertension whereas post-session results showed that participants were less likely to agree with this assertion. Conclusions Developing educational opportunities to discuss health inequities can influence perceptions of patient care.
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Affiliation(s)
- J. D. Richardson
- Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN 46202 USA
| | - H. L. Kline
- Indiana University School of Medicine, Indianapolis, IN 46202 USA
| | - B. Y. Ko
- Indiana University School of Medicine, Indianapolis, IN 46202 USA
| | - A. Hooper
- Indiana University School of Medicine, Indianapolis, IN 46202 USA
| | - S. Komanapalli
- Indiana University School of Medicine, Indianapolis, IN 46202 USA
| | | | - E.S. Yeh
- Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN 46202 USA
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11
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Testa EJ, Schmitt P, Callanan TC, Milner JD, Penvose IR, Owens BD. Angiotensin II receptor blockers and their applications in orthopaedic surgery and musculoskeletal medicine. ANNALS OF JOINT 2024; 9:39. [PMID: 39540070 PMCID: PMC11558279 DOI: 10.21037/aoj-24-12] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2024] [Accepted: 08/09/2024] [Indexed: 11/16/2024]
Abstract
Angiotensin II receptor blockers (ARBs) are commonly prescribed for hypertension and heart failure, and have well-described antifibrotic properties throughout medical literature. The etiology and pathogenesis of fibrosis is biologically complex with a multitude of factors playing a role in the process. Consequently, pathologic fibrosis may be significant within orthopaedics contributing to post-operative stiffness and, ultimately, negative patient outcomes. The pharmacology of ARBs has been described to combat fibrosis in preclinical settings, while the literature of ARBs antifibrotic properties in relation to orthopaedics remains scarce. However, fibrosis is one of the primary factors contributing to tissue healing and functional recovery in the field of orthopaedic surgery. Fibrosis has specifically been described in relation to shoulder surgery, knee arthroplasty and hip arthroscopy. As such, outcomes of various orthopaedic surgeries are dependent upon a balance between tissue healing and stiffness, both of which may be mediated by a fibrotic response. Importantly, ARBs have recently emerged as a potential therapy to combat fibrosis-mediated stiffness in orthopaedic surgery patients. Thus, the following review article seeks to highlight the basic and clinical science of ARBs with emphasis on their implications and indications for orthopaedic surgery and musculoskeletal medicine.
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Affiliation(s)
- Edward J Testa
- Department of Orthopaedic Surgery, Warren Alpert Medical School, Brown University, Providence, RI, USA
| | - Phillip Schmitt
- Department of Orthopaedic Surgery, Warren Alpert Medical School, Brown University, Providence, RI, USA
| | - Tucker C Callanan
- Department of Orthopaedic Surgery, Warren Alpert Medical School, Brown University, Providence, RI, USA
| | - John D Milner
- Department of Orthopaedic Surgery, Warren Alpert Medical School, Brown University, Providence, RI, USA
| | - Ian R Penvose
- Department of Orthopaedic Surgery, Warren Alpert Medical School, Brown University, Providence, RI, USA
| | - Brett D Owens
- Department of Orthopaedic Surgery, Warren Alpert Medical School, Brown University, Providence, RI, USA
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12
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Fukuda Y, Kawada T, Kataoka Y, Peterson J, Saku K, Alexander J, Sunagawa K. Influence of angiotensin II and telmisartan on in vivo high-resolution renal arterial impedance in rats. Am J Physiol Regul Integr Comp Physiol 2024; 327:R349-R361. [PMID: 39005079 DOI: 10.1152/ajpregu.00009.2024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2024] [Revised: 06/18/2024] [Accepted: 07/03/2024] [Indexed: 07/16/2024]
Abstract
Angiotensin II (ANG II) is known to play an important role in regulating renal hemodynamics. We sought to quantify this effect in an in vivo rat model with high-resolution renal arterial (RA) impedance. This study examines the effects of ANG II and its type 1 receptor blocker telmisartan (TELM) on RA impedance. In baroreflex-deactivated rats, we measured RA pressure (Pr) and blood flow (Fr) during random ventricular pacing to induce pressure fluctuation at three different mean Pr (60, 80, and 100 mmHg). We then estimated RA impedance as the transfer function from Fr to Pr. The RA impedance was found to align with a three-element Windkessel model consisting of proximal (Rp) and distal (Rd) resistance and compliance (C). Our study showed Rd reflected the composite characteristics of afferent and efferent arterioles. Rd increased with increasing Pr under the baseline condition with a slope of 1.03 ± 0.21 (× 10-1) min·mL-1. ANG II significantly increased the slope by 0.72 ± 0.29 (× 10-1) min·mL-1 (P < 0.05) without affecting the intercept. TELM significantly reduced the intercept by 34.49 ± 4.86 (× 10-1) mmHg·min·mL-1 (P < 0.001) from the baseline value of 37.93 ± 13.36 (× 10-1) mmHg·min·mL-1, whereas it did not affect the slope. In contrast, Rp was less sensitive than Rd to ANG II or TELM, suggesting Rp may represent the characteristics of elastic large arteries. Our findings provide valuable insights into the influence of ANG II on the dynamics of the renal vasculature.NEW & NOTEWORTHY This present method of quantifying high-resolution renal arterial impedance could contribute to elucidating the characteristics of renal vasculature influenced by physiological mechanisms, renal diseases, or pharmacological effects. The present findings help construct a lumped-parameter renal hemodynamic model that reflects the influence of angiotensin II.
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Affiliation(s)
- Yukiko Fukuda
- Medical and Health Informatics Laboratories, NTT Research, Inc., Sunnyvale, California, United States
| | - Toru Kawada
- Department of Cardiovascular Dynamics, National Cerebral and Cardiovascular Center, Osaka, Japan
| | - Yasuyuki Kataoka
- Medical and Health Informatics Laboratories, NTT Research, Inc., Sunnyvale, California, United States
| | - Jon Peterson
- Medical and Health Informatics Laboratories, NTT Research, Inc., Sunnyvale, California, United States
| | - Keita Saku
- Department of Cardiovascular Dynamics, National Cerebral and Cardiovascular Center, Osaka, Japan
- Bio Digital Twin Center, National Cerebral and Cardiovascular Center, Osaka, Japan
| | - Joe Alexander
- Medical and Health Informatics Laboratories, NTT Research, Inc., Sunnyvale, California, United States
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13
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Yoshihara F, Matsuzawa Y, Nakatsuka K, Kirigaya J, Takeuchi I, Kimura K, Konishi M, Tamura K, Fukui K, Tsukahara K, Shimizu H, Iwabuchi K, Yamada Y, Saka K, Sato Y, Ogawa M, Hayakawa K, Ohmagari N, Ikeda S, Akao M, Shimomura H, Kihara Y, Yoshimoto A, Morita M, Kumada N, Ogata S, Nishimura K, Arisato T, Matsuo M, Kishida M, Yasuda S, Ogawa H. Relationship between 2nd-generation angiotensin receptor blockers and the risk of hypotension in COVID-19 patients admitted to hospital. Hypertens Res 2024; 47:1943-1951. [PMID: 38664510 DOI: 10.1038/s41440-024-01682-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2023] [Revised: 03/04/2024] [Accepted: 03/31/2024] [Indexed: 07/03/2024]
Abstract
It has not yet been established whether angiotensin II receptor blockers (ARB), statins, and multiple drugs affect the severity of COVID-19. Therefore, we herein performed an observational study on the effects of 1st- and 2nd-generation ARB, statins, and multiple drugs, on COVID-19 in patients admitted to 15 Japanese medical facilities. The results obtained showed that ARB, statins, and multiple drugs were not associated with the primary outcome (odds ratio: 1.040, 95% confidence interval: 0.688-0.571; 0.696, 0.439-1.103; 1.056, 0.941-1.185, respectively), each component of the primary outcome (in-hospital death, ventilator support, extracorporeal membrane oxygenation support, and admission to the intensive care unit), or the secondary outcomes (oxygen administration, disturbed consciousness, and hypotension, defined as systolic blood pressure ≤90 mmHg). ARB were divided into 1st- and 2nd-generations based on their approval for use (before 2000 and after 2001), with the former consisting of losartan, candesartan, and valsartan, and the latter of telmisartan, olmesartan, irbesartan, and azilsartan. The difference of ARB generation was not associated with the primary outcome (odds ratio with 2nd-generation ARB relative to 1st-generation ARB: 1.257, 95% confidence interval: 0.613-2.574). The odd ratio for a hypotension as one of the secondary outcomes with 2nd-generation ARB was 1.754 (95% confidence interval: 1.745-1.763) relative to 1st-generation ARB. These results suggest that patients taking 2nd-generation ARB may be at a higher risk of hypotension than those taking 1st-generation ARB and also that careful observations are needed. Further studies are continuously needed to support decisions to adjust medications for co-morbidities.
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Affiliation(s)
- Fumiki Yoshihara
- Division of Nephrology and Hypertension, National Cerebral and Cardiovascular Center, Osaka, Japan.
| | - Yasushi Matsuzawa
- Division of Cardiology, Yokohama City University Medical Center, Yokohama city, Japan
- Department of Cardiovascular Medicine, Kumamoto University Hospital, Kumamoto, Japan
| | - Kiyomasa Nakatsuka
- Department of Preventive Medicine and Epidemiology, National Cerebral and Cardiovascular Center Research Institute, Suita, Osaka, Japan
| | - Jin Kirigaya
- Division of Cardiology, Yokohama City University Medical Center, Yokohama city, Japan
| | - Ichiro Takeuchi
- Advanced Critical Care and Emergency Center, Yokohama City University Medical Center, Yokohama City, Japan
| | - Kazuo Kimura
- Division of Cardiology, Yokohama City University Medical Center, Yokohama city, Japan
| | - Masaaki Konishi
- Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Kouichi Tamura
- Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan
| | - Kazuki Fukui
- Department of Cardiology, Kanagawa Cardiovascular and Respiratory Center, Yokohama, Japan
| | - Kengo Tsukahara
- Division of Cardiology, Fujisawa City Hospital, Fujisawa, Japan
| | - Hiroyuki Shimizu
- Department of Clinical Laboratory Medicine, Fujisawa City Hospital, Fujisawa, Japan
| | - Keisuke Iwabuchi
- Department of General Medicine, Kanagawa Prefectural Ashigarakami Hospital, Ashigara, Japan
| | - Yu Yamada
- Division of Cardiology, Kanagawa Prefectural Ashigarakami Hospital, Ashigara, Japan
| | - Kenichiro Saka
- Division of Cardiology, Yokosuka City Hospital, Yokosuka, Japan
| | - Yukihito Sato
- Department of Cardiology, Hyogo Prefectural Amagasaki General Medical Center, Amagasaki, Japan
| | - Masahiro Ogawa
- Department of Cardiology, Fukuoka University Hospital, Fukuoka, Japan
| | - Kayoko Hayakawa
- Disease Control and Prevention Center, National Center for Global Health and Medicine, Tokyo, Japan
| | - Norio Ohmagari
- Disease Control and Prevention Center, National Center for Global Health and Medicine, Tokyo, Japan
| | - Syuhei Ikeda
- Department of Cardiology, National Hospital Organization Kyoto Medical Center, 1-1 Mukaihata-cho, Fukakusa, Fushimi-ku, Kyoto, Japan
| | - Masaharu Akao
- Department of Cardiology, National Hospital Organization Kyoto Medical Center, 1-1 Mukaihata-cho, Fukakusa, Fushimi-ku, Kyoto, Japan
| | - Hideki Shimomura
- Division of Cardiology, Fukuoka Tokushukai Hospital, Fukuoka, Japan
| | - Yasuki Kihara
- Kobe City Medical Center General Hospital, 2-1-1, Minamimachi, Minatojima, Chuoku, Kobe, Hyogo, Japan
| | - Akihiro Yoshimoto
- Department of Nephrology, Kobe City Medical Center General Hospital, Kobe, Japan
| | - Masanori Morita
- Critical Care Medical Center Sakai City Medical Center, Sakai, Japan
| | - Norihiko Kumada
- Department of Urology, Suita Municipal Hospital, Suita, Japan
| | - Soshiro Ogata
- Department of Preventive Medicine and Epidemiology, National Cerebral and Cardiovascular Center Research Institute, Suita, Osaka, Japan
| | - Kunihiro Nishimura
- Department of Preventive Medicine and Epidemiology, National Cerebral and Cardiovascular Center Research Institute, Suita, Osaka, Japan
| | - Tetsuya Arisato
- Division of Nephrology and Hypertension, National Cerebral and Cardiovascular Center, Osaka, Japan
| | - Miki Matsuo
- Division of Nephrology and Hypertension, National Cerebral and Cardiovascular Center, Osaka, Japan
| | - Masatsugu Kishida
- Division of Nephrology and Hypertension, National Cerebral and Cardiovascular Center, Osaka, Japan
| | - Satoshi Yasuda
- Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan
- Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan
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Twala NMS, Tade G, Dessein PH, Teckie G. Causes of Chronic Kidney Disease and Their Associations with Cardiovascular Risk and Disease in a Sub-Saharan Low-Income Population. Int J Nephrol Renovasc Dis 2024; 17:175-195. [PMID: 38882658 PMCID: PMC11180468 DOI: 10.2147/ijnrd.s463751] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2024] [Accepted: 05/15/2024] [Indexed: 06/18/2024] Open
Abstract
Introduction The causes of chronic kidney disease (CKD) in people living in Sub-Saharan Africa await identification. Also, whether cardiovascular risk and disease extent differ among patients with different CKD etiologies is uncertain. Methods In this prospective cross-sectional study, we examined the presumed causes of chronic kidney disease (CKD) and their relationships with cardiovascular risk and disease in 743 consecutive patients from a sub-Saharan low-income population. Results Hypertensive nephropathy (HNP) (60.2%), diabetic nephropathy (DNP) (24.4%), HIV associated CKD (20.0%) and glomerular disease (13.6%) comprised the major CKD etiologies upon enrolment at the hospital nephrology clinic. Pulse pressure was larger in patients with concurrent HNP and DNP than in those with HNP only (p<0.001). Pulse pressure and systolic blood pressure were larger in HNP or/and DNP patients than those with HIV associated CKD and glomerular disease (p=0.04 to <0.001). Cardiovascular disease was more prevalent in patients with HNP and concurrent HNP and DNP than those from other etiologic categories (p<0.05). HNP and DNP were associated with pulsatile pressures (pulse pressure and systolic blood pressure) independent of one another (p<0.01). In adjusted product of coefficient mediation analysis, mean arterial or distending pressure accounted fully for the potential impact of HNP on pulsatile pressures (103.9-115.7%) but not for that of DNP on the respective pressures (-2.0%-(-)7.5%). Conclusion HNP is by far the most prevalent presumed cause of CKD in this African population. Cardiovascular risk and disease differ markedly across CKD etiological categories.
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Affiliation(s)
- Nkosingiphile Matthew Sandile Twala
- Department of Medicine, Chris Hani Baragwanath Hospital and Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa
| | - Grace Tade
- Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa
| | - Patrick Hector Dessein
- Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa
- Internal Medicine Department, Rheumatology division, University of Witwatersrand, Johannesburg, South Africa
| | - Gloria Teckie
- Department of Medicine, Chris Hani Baragwanath Hospital and Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa
- Division of Nephrology, Department of Medicine, Chris Hani Baragwanath Academic Hospital and Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa
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15
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Minvielle Moncla LH, Briend M, Sokhna Sylla M, Mathieu S, Rufiange A, Bossé Y, Mathieu P. Mendelian randomization reveals interactions of the blood proteome and immunome in mitral valve prolapse. COMMUNICATIONS MEDICINE 2024; 4:108. [PMID: 38844506 PMCID: PMC11156961 DOI: 10.1038/s43856-024-00530-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2023] [Accepted: 05/21/2024] [Indexed: 06/09/2024] Open
Abstract
BACKGROUND Mitral valve prolapse (MVP) is a common heart disorder characterized by an excessive production of proteoglycans and extracellular matrix in mitral valve leaflets. Large-scale genome-wide association study (GWAS) underlined that MVP is heritable. The molecular underpinnings of the disease remain largely unknown. METHODS We interrogated cross-modality data totaling more than 500,000 subjects including GWAS, 4809 molecules of the blood proteome, and genome-wide expression of mitral valves to identify candidate drivers of MVP. Data were investigated through Mendelian randomization, network analysis, ligand-receptor inference and digital cell quantification. RESULTS In this study, Mendelian randomization identify that 33 blood proteins, enriched in networks for immunity, are associated with the risk of MVP. MVP- associated blood proteins are enriched in ligands for which their cognate receptors are differentially expressed in mitral valve leaflets during MVP and enriched in cardiac endothelial cells and macrophages. MVP-associated blood proteins are involved in the renewal-polarization of macrophages and regulation of adaptive immune response. Cytokine activity profiling and digital cell quantification show in MVP a shift toward cytokine signature promoting M2 macrophage polarization. Assessment of druggability identify CSF1R, CX3CR1, CCR6, IL33, MMP8, ENPEP and angiotensin receptors as actionable targets in MVP. CONCLUSIONS Hence, integrative analysis identifies networks of candidate molecules and cells involved in immune control and remodeling of the extracellular matrix, which drive the risk of MVP.
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Affiliation(s)
| | - Mewen Briend
- Genomic Medicine Laboratory, Quebec Heart and Lung Institute, Laval University, Quebec City, QC, Canada
| | - Mame Sokhna Sylla
- Genomic Medicine Laboratory, Quebec Heart and Lung Institute, Laval University, Quebec City, QC, Canada
| | - Samuel Mathieu
- Genomic Medicine Laboratory, Quebec Heart and Lung Institute, Laval University, Quebec City, QC, Canada
| | - Anne Rufiange
- Genomic Medicine Laboratory, Quebec Heart and Lung Institute, Laval University, Quebec City, QC, Canada
| | - Yohan Bossé
- Department of Molecular Medicine, Laval University, Quebec City, QC, Canada
| | - Patrick Mathieu
- Genomic Medicine Laboratory, Quebec Heart and Lung Institute, Laval University, Quebec City, QC, Canada.
- Department of Surgery, Laval University, Quebec City, QC, Canada.
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Li X, Bijlsma MJ, de Vos S, Bos JHJ, Mubarik S, Schuiling-Veninga CCM, Hak E. Comparative effectiveness of antihypertensive monotherapies in primary prevention of cardiovascular events-a real-world longitudinal inception cohort study. Front Pharmacol 2024; 15:1357567. [PMID: 38903996 PMCID: PMC11188318 DOI: 10.3389/fphar.2024.1357567] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2023] [Accepted: 05/13/2024] [Indexed: 06/22/2024] Open
Abstract
Introduction Antihypertensive drugs are used preventatively to lower the risk of cardiovascular disease events. Comparative effectiveness studies on angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), beta-blockers (BBs), calcium channel blockers (CCBs), and thiazides have yielded inconsistent results and given little consideration to patient adherence. Using a longitudinal cohort and considering time-varying adherence and confounding factors, we aimed to estimate the real-world effectiveness of five major antihypertensive drug monotherapies in the primary prevention of cardiovascular events. Methods Eligible patients for a retrospective inception cohort study were selected using information obtained from the University of Groningen IADB.nl pharmacy prescription database. Cohort 1 comprised adherent patients with a follow-up time exceeding 1 year, and cohort 2 comprised all patients independent of adherence. The exposures were ACEIs, ARBs, BBs, CCBs, and thiazides. The primary outcome was the time to the first prescription for an acute cardiac drug therapy (CDT) measured using valid drug proxies to identify the first major cardiovascular event. A per-protocol analytical approach was adopted with inverse probability of treatment weighted (IPTW), time-varying Cox regression analysis to obtain the hazard ratios (HRs) and 95% confidence intervals (CIs). Results In cohort 1 (n = 22,441), 1,294 patients (5.8%) were prescribed an acute CDT with an average follow-up time of 4.2 ± 2.8 years. Following IPTW, the hazard measures of ARBs and thiazides were lower than those of BBs (HRs: 0.79 and 0.80, respectively; 95% CIs: 0.64-0.97 and 0.69-0.94, respectively). Among drug-treated diabetic patients, the hazard measures were even lower, with HR point estimates of 0.43 (CI: 0.19-0.98) for ARBs and 0.32 (CI: 0.13-0.82) for thiazides. In cohort 2 (n = 33,427) and sensitivity analysis, the comparative effectiveness results for thiazides and BBs were similar to those for cohort 1. Conclusion The findings of this real-world analysis suggest that the incidence of CDT associated with long-term thiazide or ARB monotherapy is lower than the incidence of CDT with BBs, notably among high-risk patients. Incidences of CDT associated with ACEIs and CCBs were comparable relative to those associated with BBs.
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Affiliation(s)
- Xuechun Li
- PharmacoTherapy, Epidemiology and Economics, Groningen Research Institute of Pharmacy, University of Groningen, Groningen, Netherlands
| | - Maarten J. Bijlsma
- PharmacoTherapy, Epidemiology and Economics, Groningen Research Institute of Pharmacy, University of Groningen, Groningen, Netherlands
- Max Planck Institute for Demographic Research, Rostock, Germany
| | - Stijn de Vos
- PharmacoTherapy, Epidemiology and Economics, Groningen Research Institute of Pharmacy, University of Groningen, Groningen, Netherlands
| | - Jens H. J. Bos
- PharmacoTherapy, Epidemiology and Economics, Groningen Research Institute of Pharmacy, University of Groningen, Groningen, Netherlands
| | - Sumaira Mubarik
- PharmacoTherapy, Epidemiology and Economics, Groningen Research Institute of Pharmacy, University of Groningen, Groningen, Netherlands
| | - Catharina C. M. Schuiling-Veninga
- PharmacoTherapy, Epidemiology and Economics, Groningen Research Institute of Pharmacy, University of Groningen, Groningen, Netherlands
| | - Eelko Hak
- PharmacoTherapy, Epidemiology and Economics, Groningen Research Institute of Pharmacy, University of Groningen, Groningen, Netherlands
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17
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Fadaly WAA, Elshaier YAMM, Ali FEM, El-Bahrawy AH, Abdellatif KRA, Nemr MTM. Vicinal diaryl pyrazole with tetrazole/urea scaffolds as selective angiotensin converting enzyme-1/cyclooxygenase-2 inhibitors: Design, synthesis, anti-hypertensive, anti-fibrotic, and anti-inflammatory. Drug Dev Res 2024; 85:e22217. [PMID: 38845214 DOI: 10.1002/ddr.22217] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2024] [Revised: 05/05/2024] [Accepted: 05/18/2024] [Indexed: 06/15/2024]
Abstract
As a hybrid weapon, two novel series of pyrazoles, 16a-f and 17a-f, targeting both COX-2 and ACE-1-N-domain, were created and their anti-inflammatory, anti-hypertensive, and anti-fibrotic properties were evaluated. In vitro, 17b and 17f showed COX-2 selectivity (SI = 534.22 and 491.90, respectively) compared to celecoxib (SI = 326.66) and NF-κB (IC50 1.87 and 2.03 μM, respectively). 17b (IC50 0.078 μM) and 17 f (IC50 0.094 μM) inhibited ACE-1 comparable to perindopril (PER) (IC50 0.048 μM). In vivo, 17b decreased systolic blood pressure by 18.6%, 17b and 17f increased serum NO levels by 345.8%, and 183.2%, respectively, increased eNOS expression by 0.97 and 0.52 folds, respectively and reduced NF-κB-p65 and P38-MAPK expression by -0.62, -0.22, -0.53, and -0.24 folds, respectively compared to l-NAME (-0.34, -0.45 folds decline in NF-κB-p65 and P38-MAPK, respectively). 17b reduced ANG-II expression which significantly reversed the cardiac histological changes induced by L-NAME.
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Affiliation(s)
- Wael A A Fadaly
- Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt
| | - Yaseen A M M Elshaier
- Organic & Medicinal Chemistry Department, Faculty of Pharmacy, University of Sadat City, Menoufia, Egypt
| | - Fares E M Ali
- Department of Pharmacology & Toxicology, Faculty of Pharmacy, Al-Azhar University, Assiut Branch, Assiut, Egypt
| | - Ali H El-Bahrawy
- Department of Clinical Pharmacy, Faculty of Pharmacy, Al-Azhar University, Assiut Branch, Assiut, Egypt
| | - Khaled R A Abdellatif
- Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt
- Pharmaceutical Sciences Department, Ibn Sina National College for Medical Studies, Jeddah, Kingdom of Saudi Arabia
| | - Mohamed T M Nemr
- Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt
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18
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MacLaughlin EJ, Saseen JJ. It's About Blood Pressure Reduction and Control. Am J Hypertens 2024; 37:396-398. [PMID: 38447001 DOI: 10.1093/ajh/hpae023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2024] [Accepted: 03/03/2024] [Indexed: 03/08/2024] Open
Affiliation(s)
- Eric J MacLaughlin
- Department of Pharmacy Practice, Texas Tech University Health Sciences Center Jerry H. Hodge School of Pharmacy, Amarillo, Texas, USA
- Department of Community and Family Medicine, Texas Tech University Health Sciences Center School of Medicine, Amarillo, Texas, USA
- Department of Internal Medicine, Texas Tech University Health Sciences Center School of Medicine, Amarillo, Texas, USA
| | - Joseph J Saseen
- Department of Clinical Pharmacy, University of Colorado Anschutz Medical Campus Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, Colorado, USA
- Department of Family Medicine, University of Colorado Anschutz Medical Campus School of Medicine, Aurora, Colorado, USA
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Yoo YG, Lim MJ, Kim JS, Jeong HE, Ko H, Shin JY. Risk of myocardial infarction, heart failure, and cerebrovascular disease with the use of valsartan, losartan, irbesartan, and telmisartan in patients. Medicine (Baltimore) 2023; 102:e36098. [PMID: 37986329 PMCID: PMC10659604 DOI: 10.1097/md.0000000000036098] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/11/2023] [Revised: 09/23/2023] [Accepted: 10/23/2023] [Indexed: 11/22/2023] Open
Abstract
There is a lack of studies comparing the risk of cardio-cerebrovascular disease between angiotensin receptor blockers (ARBs) of different half-lives. We aimed to compare the risks of myocardial infarction (MI), heart failure (HF), and cerebrovascular disease with the use of valsartan, losartan, irbesartan, and telmisartan with different half-lives in a national claim-based retrospective cohort of patients aged ≥ 40 years with hypertension. To establish a cohort exposed to valsartan, losartan, irbesartan, or telmisartan, we performed propensity score (PS) matching and used an as-treated approach to evaluate exposure. The Cox regression model was employed to calculate hazard ratios, which were based on the incidence rate for each newly occurring event of MI, heart failure, or cerebrovascular disease. These hazard ratios were calculated to compare the risk of MI, heart failure, and cerebrovascular disease associated with valsartan, losartan, and irbesartan in comparison to telmisartan. A PS-matched cohort of 148,229 patients was established for each of valsartan, losartan, irbesartan, or telmisartan. The matched cohort analysis showed that the adjusted hazard ratio (aHRs, 95% confidence interval) for MI was higher for valsartan use (1.39, 1.33-1.45) and losartan use (1.10, 1.05-1.15) but lower for irbesartan use (0.90, 0.86-0.94) compared with the reference (telmisartan). The aHRs for HF were not different among these ARBs (angiotensin receptor blockers). The aHR for cerebrovascular disease was lower for valsartan use (0.85, 0.83-0.87) and losartan use (0.80, 0.78-0.82) but higher for irbesartan use (1.11, 1.09-1.13) compared with the reference. We found differences in the risk of MI and cerebrovascular disease with the use of different ARBs compared to telmisartan use. Valsartan, and losartan with a short half-life, which showed a higher risk of MI, had a lower risk of cerebrovascular disease. Conversely, irbesartan with a long half-life, which showed a lower risk of MI, had a higher risk of cerebrovascular disease.
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Affiliation(s)
- Yung-Geun Yoo
- School of Pharmacy, Sungkyunkwan University, Suwon, South Korea
| | - Min-Jung Lim
- School of Pharmacy, Sungkyunkwan University, Suwon, South Korea
- Department of Biohealth Regulatory Science, Sungkyunkwan University, Suwon, South Korea
| | - Jin-Seob Kim
- School of Pharmacy, Sungkyunkwan University, Suwon, South Korea
- Department of Biohealth Regulatory Science, Sungkyunkwan University, Suwon, South Korea
| | - Han-Eol Jeong
- School of Pharmacy, Sungkyunkwan University, Suwon, South Korea
- Department of Biohealth Regulatory Science, Sungkyunkwan University, Suwon, South Korea
| | - HeeJoo Ko
- College of Medicine, The Catholic University of Korea, Seoul, South Korea
| | - Ju-Young Shin
- School of Pharmacy, Sungkyunkwan University, Suwon, South Korea
- Department of Biohealth Regulatory Science, Sungkyunkwan University, Suwon, South Korea
- Department of Clinical Research Design and Evaluation, Samsung Advanced Institute for Health Science & Technology, Sungkyunkwan University, Seoul, South Korea
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20
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Dahlqvist C, Delaunois L, Demeure F. Sartan-induced interstitial lung disease. Respir Med Case Rep 2023; 46:101946. [PMID: 38025246 PMCID: PMC10663810 DOI: 10.1016/j.rmcr.2023.101946] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2023] [Accepted: 11/01/2023] [Indexed: 12/01/2023] Open
Abstract
Background Lung toxicity of angiotensin receptor blockers (sartans) have very seldom been reported in the literature despite their wide use. We here report a case of interstitial lung disease elicited by sartans, with two episodes induced by two different sartans at 10 years of interval. Case presentation In 2012, eprosartan was the very likely cause of a drug induced interstitial lung disease in a 60 year old man. Indeed, his symptoms, consisting in a MMRC2 dyspnea and recurrent hemoptysis, completely disappeared after the removal of this drug. When the circumstances rendered it necessary to start another angiotensin receptor blocker (namely valsartan) ten years later we did not expect the same reaction to occur given among other things a very poor literature on the topic. After a few months with this medication, he however developed similar symptoms and a Chest CT imaging that was comparable to what he had in 2012.This time also the clinical picture resolved completely when the sartan was stopped. Conclusion We report this first case of a drug induced interstitial lung disease induced by two different angiotensin receptor blockers (sartans) with a new drug challenge ten years after the first one.
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Haji Ali B, Shirvaliloo M, Fathi-Karkan S, Mirinejad S, Ulucan-Karnak F, Sargazi S, Sargazi S, Sheervalilou R, Rahman MM. Nanotechnology-Based Strategies for Extended-Release Delivery of Angiotensin Receptor Blockers (ARBs): A Comprehensive Review. Chem Biodivers 2023; 20:e202301157. [PMID: 37796134 DOI: 10.1002/cbdv.202301157] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2023] [Revised: 09/30/2023] [Accepted: 10/05/2023] [Indexed: 10/06/2023]
Abstract
There has been a significant shift in the perception of hypertension as an important contributor to the global disease burden. Approximately 6 % and 8 % of pregnancies are affected by hypertension, which can adversely affect the mother and the fetus. Furthermore, a hypertensive individual is at increased risk of developing kidney disease, arterial hardening, eye damage, and strokes. Using angiotensin receptor blockers (ARBs) is widespread in treating hypertension, heart failure, coronary artery disease, and diabetic nephropathy. Despite this, some ARBs have limited use due to their poor oral bioavailability and water solubility. To tackle this, a variety of nanoparticle (NP)-based systems, such as polymeric NPs (i. e., dendrimers), polymeric micelles, polymer-drug conjugates, lipid NPs, nanoemulsions, self-emulsifying drug delivery systems (SEDDS), solid lipid NPs (SLNs), nanostructured lipid carriers (NLCs), carbon-based nanocarriers, inorganic NPs, and nanocrystals, have been recently developed for efficient delivery of losartan, Valsartan (Val), Olmesartan (OLM), Telmisartan (TEL), Candesartan, Eprosartan, Irbesartan, and Azilsartan to target cells. This review article provides a literature-based comparison of the various classes of ARBs, their mechanisms of action, and an overview of the nanoformulations developed for ARB delivery and successfully applied to managing hypertension, diabetic complications, and other conditions.
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Affiliation(s)
- Bahareh Haji Ali
- Department of Medical Physics, Iran University of Medical Sciences, Tehran, Iran
| | - Milad Shirvaliloo
- Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Sonia Fathi-Karkan
- Natural Products and Medicinal Plants Research Center, North Khorasan University of Medical Sciences, Bojnurd, 9453155166, Iran
- Department of Advanced Sciences and Technologies in Medicine, School of Medicine, North Khorasan University of Medical Sciences, Bojnurd, 9414974877, Iran
| | - Shekoufeh Mirinejad
- Cellular and Molecular Research Center, Research Institute of Cellular and Molecular Sciences in Infectious Diseases, Zahedan University of Medical Sciences, Zahedan, Iran
| | - Fulden Ulucan-Karnak
- Department of Medical Biochemistry, Institute of Health Sciences, Ege University, İzmir, 35100, Turkey
| | - Saman Sargazi
- Cellular and Molecular Research Center, Research Institute of Cellular and Molecular Sciences in Infectious Diseases, Zahedan University of Medical Sciences, Zahedan, Iran, Department of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran
| | - Sara Sargazi
- Cellular and Molecular Research Center, Research Institute of Cellular and Molecular Sciences in Infectious Diseases, Zahedan University of Medical Sciences, Zahedan, Iran
| | - Roghayeh Sheervalilou
- Pharmacology Research Center, Zahedan University of Medical Sciences, Zahedan, 9816743463, Iran
| | - Mohammed M Rahman
- Center of Excellence for Advanced Materials Research (CEAMR) & Department of Chemistry, Faculty of Science, King Abdulaziz University, Jeddah, 21589, Saudi Arabia
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22
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Dagher YG, El Helou S, Haifa KG, Chalhoub IG, Boulos RT, Atallah B, Nasr F, Kassab I, Chahine MN. The association between angiotensin receptor blockers and lung, bladder, and colon cancer development: A 10-year multicentric retrospective Lebanese study. Medicine (Baltimore) 2023; 102:e34901. [PMID: 37682163 PMCID: PMC10489396 DOI: 10.1097/md.0000000000034901] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2023] [Accepted: 08/03/2023] [Indexed: 09/09/2023] Open
Abstract
Cardiovascular diseases (CVD) are the leading cause of death globally, followed by cancer. Angiotensin II contributes greatly to CVD pathogenesis, and Angiotensin II receptor blockers (ARBs) constitute a mainstay in hypertension and CVD management. However, the relationship between ARBs and cancer initiation is controversial, with no clear data in Lebanon. Therefore, our study aimed to determine the association between ARBs intake and lung, bladder, and colorectal cancers development in the Lebanese population. A retrospective study was conducted on 709 subjects divided into 2 main groups: Control (subjects without cancer; n = 177), and Cases (patients with cancer (n = 532): lung, bladder, or colorectal), taking ARBs (n = 236, (n = 121 in control and n = 115 in cases)) or not (n = 473). Collected information included the patients demographics, comorbidities, cancer's risk factors, and ARBs dose and duration intake. Bivariate, multivariate, and binary logistic analyses were enrolled. ARBs use was significantly protective (P value = 0.000) against overall cancer development (odds ratio [OR] = 0.127) and against each, lung (OR < 1), bladder (OR < 1), and colorectal cancers (OR < 1). A duration-response relationship was established. This protective effect and the time-dependent relationship remained unchanged after omitting the most relevant risk factors. In summary, a significant overall protective effect of ARBs against lung, bladder and colorectal cancers was found. This beneficial response was time-dependent. These results can guide patients on treatment options and clinicians for informed decision-making.
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Affiliation(s)
- Yara G. Dagher
- Faculty of Medical Sciences, Lebanese University, Hadath, Lebanon
| | - Sandra El Helou
- Faculty of Medical Sciences, Lebanese University, Hadath, Lebanon
| | - Karen G. Haifa
- Faculty of Medical Sciences, Lebanese University, Hadath, Lebanon
| | | | - Rita T. Boulos
- Faculty of Medical Sciences, Lebanese University, Hadath, Lebanon
| | | | - Fadi Nasr
- Faculty of Medical Sciences, Lebanese University, Hadath, Lebanon
- Hematology-Oncology Department, Hotel Dieu DE France, Achrafieh, Beirut, Lebanon
| | - Issam Kassab
- National Center of Pharmacovigilance, Faculty of Pharmacy, Lebanese University, Hadath, Lebanon
| | - Mirna N. Chahine
- Faculty of Medical Sciences, Lebanese University, Hadath, Lebanon
- Basic Sciences Department, Faculty of Medical Sciences, Lebanese University, Hadath, Lebanon
- Foundation-Medical Research Institutes (F-MRI), Beirut, Lebanon/Geneva, Switzerland
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23
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Garcia-Tarazona YM, Morantes SJ, Gordillo JFI, Sepúlveda P, Ramos FA, Lafaurie GI. Candesartan exhibits low intrinsic permeation capacity and affects buccal tissue viability and integrity: An ex vivo study in porcine buccal mucosa. Eur J Pharm Sci 2023; 188:106495. [PMID: 37329923 DOI: 10.1016/j.ejps.2023.106495] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2022] [Revised: 06/12/2023] [Accepted: 06/14/2023] [Indexed: 06/19/2023]
Abstract
Candesartan is a nonpeptide angiotensin II receptor blocker that selectively binds to angiotensin II receptor subtype 1. It is administered orally in its ester form (candesartan cilexetil). However, its poor aqueous solubility results in its low bioavailability; therefore, other routes of administration must be explored. The buccal mucosa has been extensively studied as an alternative route for drug delivery as it improves the bioavailability of drugs administered via the peroral route. Porcine buccal mucosa has been widely used as an ex vivo model to study the permeability of various diffusants; however, studies on candesartan are limited. This study aimed to evaluate the ex vivo permeation profile of candesartan and its effects on the viability and integrity of porcine buccal mucosa. Initially, we evaluated the viability, integrity, and barrier function of the buccal tissue before performing permeability tests using freshly excised tissues or tissues after 12 h of resection. Here, three indicators were used: caffeine, β-estradiol, and FD-20 penetration; mucosal metabolic activity, as determined using MTT reduction assay; and haematoxylin and eosin staining. Our results indicated that the porcine buccal mucosa preserved its viability, integrity, and barrier function before the permeation assay, allowing the passage of molecules with a molecular mass of less than 20 kDa, such as caffeine, but not β-estradiol and FD-20. Furthermore, we analyzed the intrinsic capacity of candesartan to diffuse through the fresh porcine buccal mucosa under two pH conditions. The concentration of candesartan in the receptor chamber of Franz diffusion cell was quantified using ultra-high liquid chromatography. In the permeation assay, candesartan exhibited a low intrinsic permeation capacity that impacted the buccal tissue viability and integrity, suggesting that using the buccal mucosa as an alternative route of administration requires developing a pharmaceutical formulation that reduces the adverse effects on mucosa and increasing the buccal permeability of candesartan.
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Affiliation(s)
- Yenny M Garcia-Tarazona
- Universidad El Bosque, Unidad de Investigación Básica Oral UIBO, Bogotá, Colombia; Universidad El Bosque, Facultad de Odontología, Maestría en Ciencias Odontológicas, Bogotá, Colombia
| | - Sandra Johanna Morantes
- Universidad El Bosque, Unidad de Investigación Básica Oral UIBO, Bogotá, Colombia; Facultad de Ciencias, Programa Química Farmacéutica, Grupo de Investigación en Química Aplicada INQA, Universidad El Bosque, Bogotá, Colombia.
| | | | - Paula Sepúlveda
- Facultad de Ciencias, Departamento de Farmacia, Universidad Nacional de Colombia, Bogotá, Colombia
| | - Freddy A Ramos
- Facultad de Ciencias, Departamento de Química, Universidad Nacional de Colombia, Bogotá, Colombia
| | - Gloria Inés Lafaurie
- Universidad El Bosque, Unidad de Investigación Básica Oral UIBO, Bogotá, Colombia
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Bager JE, Manhem K, Andersson T, Hjerpe P, Bengtsson-Boström K, Ljungman C, Mourtzinis G. Hypertension: sex-related differences in drug treatment, prevalence and blood pressure control in primary care. J Hum Hypertens 2023; 37:662-670. [PMID: 36658330 PMCID: PMC10403353 DOI: 10.1038/s41371-023-00801-5] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2022] [Revised: 12/15/2022] [Accepted: 01/05/2023] [Indexed: 01/20/2023]
Abstract
Antihypertensive treatment is equally beneficial for reducing cardiovascular risk in both men and women. Despite this, the drug treatment, prevalence and control of hypertension differ between men and women. Men and women respond differently, particularly with respect to the risk of adverse events, to many antihypertensive drugs. Certain antihypertensive drugs may also be especially beneficial in the setting of certain comorbidities - of both cardiovascular and extracardiac nature - which also differ between men and women. Furthermore, hypertension in pregnancy can pose a considerable therapeutic challenge for women and their physicians in primary care. In addition, data from population-based studies and from real-world data are inconsistent regarding whether men or women attain hypertension-related goals to a higher degree. In population-based studies, women with hypertension have higher rates of treatment and controlled blood pressure than men, whereas real-world, primary-care data instead show better blood pressure control in men. Men and women are also treated with different antihypertensive drugs: women use more thiazide diuretics and men use more angiotensin-enzyme inhibitors and calcium-channel blockers. This narrative review explores these sex-related differences with guidance from current literature. It also features original data from a large, Swedish primary-care register, which showed that blood pressure control was better in women than men until they reached their late sixties, after which the situation was reversed. This age-related decrease in blood pressure control in women was not, however, accompanied by a proportional increase in use of antihypertensive drugs and female sex was a significant predictor of less intensive antihypertensive treatment.
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Affiliation(s)
- Johan-Emil Bager
- Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
- Department of Emergency Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden.
| | - Karin Manhem
- Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Department of Emergency Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Tobias Andersson
- Primary Health Care, School of Public Health and Community Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Regionhälsan R&D Centre, Skaraborg Primary Care, Skövde, Sweden
| | - Per Hjerpe
- Primary Health Care, School of Public Health and Community Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Regionhälsan R&D Centre, Skaraborg Primary Care, Skövde, Sweden
| | - Kristina Bengtsson-Boström
- Primary Health Care, School of Public Health and Community Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Regionhälsan R&D Centre, Skaraborg Primary Care, Skövde, Sweden
| | - Charlotta Ljungman
- Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Georgios Mourtzinis
- Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Department of Medicine and Emergency Mölndal, Sahlgrenska University Hospital, Gothenburg, Sweden
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25
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Wang Z, Wang S, Zhang L, Wang J, Wang R, Chen S, Shi Q, Wu H, Wang L, Li N. Two-Drug Combinations Therapy of Different Doses of Valsartan Existing Diverse Significance for Hypertensive Patients. Rev Cardiovasc Med 2023; 24:187. [PMID: 39077003 PMCID: PMC11266496 DOI: 10.31083/j.rcm2407187] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2022] [Revised: 02/17/2023] [Accepted: 02/20/2023] [Indexed: 07/31/2024] Open
Abstract
Background The incidence of hypertension and clinical complications (e.g., heart, cerebrovascular and kidney injury) is increasing worldwide. It is widely known that a relatively large dose of valsartan (320 mg) could alleviate clinical complications. The current network meta-analysis assessed which drug could be combined with a relatively large dose of valsartan to control blood pressure (BP) more effectively. And which combination therapy with different dosages of valsartan did not induce excessive BP reduction with increasing dosages of valsartan. Methods The PubMed, Embase, Medline, Cochrane Library, CNKI, Wanfang, and CSTJ databases were searched from inception to October 2022 for relevant randomized controlled trials (RCTs). The search strategies included concepts related to hypertension and two-drug combination therapy of different doses of valsartan, and there were no language or data restrictions. The outcomes included adverse effects and changes in systolic BP and diastolic BP. Permanent discontinuations related to treatment were the most accurate and objective measure of adverse effects. The common adverse effects of most studies (i.e., dizziness, headache, nasopharyngitis, asthenia and urticaria) were also included. A Bayesian network meta-analysis was performed, and mean differences with 95% confidence intervals were calculated. ADDIS and STATA were used for Bayesian model network meta-calculation. Results Thirty-four RCTs were included involving 26,752 patients, and the interventions included different doses of valsartan combined with various types and doses of drugs. Among many combination therapies, the combination of valsartan 320 mg with amlodipine 10 mg (p < 0.01) had the best antihypertensive effect without significant adverse effects. Compared with valsartan 80 mg and 160 mg, valsartan 320 mg combined with hydrochlorothiazide 25 mg (p > 0.05) did not further reduce BP and was not shown to increase the incidence of adverse effects. Conclusions Combination therapy with a relatively large dose of valsartan could control BP and improve clinical complications effectively. However, for hypertensive patients with different treatment requirements, specific choices should be made regarding whether to control BP, treat clinical complications, or both.
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Affiliation(s)
- Zerong Wang
- The Second Clinical Medical College, Lanzhou University, 730000 Lanzhou, Gansu, China
| | - Shixiong Wang
- Department of Cardiac Surgery, Lanzhou University Second Hospital, 730030 Lanzhou, Gansu, China
| | - Liqiong Zhang
- The Second Clinical Medical College, Lanzhou University, 730000 Lanzhou, Gansu, China
| | - Jiaxuan Wang
- The Second Clinical Medical College, Lanzhou University, 730000 Lanzhou, Gansu, China
| | - Rong Wang
- The Second Clinical Medical College, Lanzhou University, 730000 Lanzhou, Gansu, China
| | - Shude Chen
- The Second Clinical Medical College, Lanzhou University, 730000 Lanzhou, Gansu, China
| | - Qiling Shi
- The Second Clinical Medical College, Lanzhou University, 730000 Lanzhou, Gansu, China
| | - Hongye Wu
- The Second Clinical Medical College, Lanzhou University, 730000 Lanzhou, Gansu, China
| | - Liuyang Wang
- The Second Clinical Medical College, Lanzhou University, 730000 Lanzhou, Gansu, China
| | - Ningyin Li
- Cardiovascular Department, Lanzhou University Second Hospital, 730030 Lanzhou, Gansu, China
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26
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Kim JD, Fisher A, Dormuth CR. Trends in antihypertensive drug utilization in British Columbia, 2004-2019: a descriptive study. CMAJ Open 2023; 11:E662-E671. [PMID: 37527901 PMCID: PMC10400081 DOI: 10.9778/cmajo.20220023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 08/03/2023] Open
Abstract
BACKGROUND Clinical guidelines for hypertension were updated with lower blood pressure targets following new studies in 2015; the real-world impact of these changes on antihypertensive drug use is unknown. We aimed to describe trends in antihypertensive drug utilization from 2004 to 2019 in British Columbia. METHODS We conducted a longitudinal study to describe the annual prevalence and incidence rate of use of 5 antihypertensive drug classes (thiazides, angiotensin-converting enzyme [ACE] inhibitors, angiotensin II receptor blockers [ARBs], calcium channel blockers and β-blockers) among BC residents aged 30-75 years. We also conducted a cohort study to compare the risk of discontinuation and switch or add-on therapy between incident users of the above drug classes. We used linkable administrative health databases from BC. We performed a Fine-Gray competing risk analysis to estimate subhazard ratios. RESULTS Among BC residents aged 30-75 years (population: 2 376 282 [2004] to 3 014 273 [2019]), the incidence rate of antihypertensive drug use decreased from 23.7 per 1000 person-years in 2004 to 18.3 per 1000 person-years in 2014, and subsequently increased to 22.6 per 1000 person-years in 2019. The incidence rate of thiazide use decreased from 8.9 per 1000 person-years in 2004 to 3.2 per 1000 person-years in 2019, and incidence rates for the other drug classes increased. Incident users receiving thiazide monotherapy had an increased risk of discontinuing any antihypertensive treatment compared with ACE inhibitor monotherapy (subhazard ratio 0.96, 95% confidence interval [CI] 0.95-0.97), ARB monotherapy (subhazard ratio 0.84, 95% CI 0.81-0.87) and thiazide combination with ACE inhibitor or ARB (subhazard ratio 0.86, 95% CI 0.84-0.88), and had the highest risk of switching or adding on. INTERPRETATION First-line use of thiazides continued to decrease despite a marked increase in incident antihypertensive therapy following updated guidelines; incident users receiving ARB monotherapy were least likely to discontinue, and incident users receiving thiazide monotherapy were more likely to switch or add on than users of other initial monotherapy or combination. Further research is needed on the factors influencing treatment decisions to understand the differences in trends and patterns of antihypertensive drug use.
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Affiliation(s)
- Jason D Kim
- Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver, BC
| | - Anat Fisher
- Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver, BC
| | - Colin R Dormuth
- Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver, BC
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27
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Kim J, Kang D, Kim SE, Park H, Park TK, Lee JM, Yang JH, Song YB, Choi JH, Choi SH, Gwon HC, Guallar E, Cho J, Hahn JY. Comparison Between Fimasartan Versus Other Angiotensin Receptor Blockers in Patients With Heart Failure After Acute Myocardial Infarction. J Korean Med Sci 2023; 38:e202. [PMID: 37365730 PMCID: PMC10293657 DOI: 10.3346/jkms.2023.38.e202] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2022] [Accepted: 03/08/2023] [Indexed: 06/28/2023] Open
Abstract
BACKGROUNDS Fimasartan is the most recently developed, potent, and long-acting angiotensin II receptor blocker (ARB). However, data are limited regarding treatment effects of fimasartan in patients with heart failure. METHODS Between 2010 and 2016, patients who underwent coronary revascularization for myocardial infarction (MI) with heart failure and prescription of ARB at hospital discharge were enrolled from the Korean nationwide medical insurance data. Clinical outcomes were compared between patients receiving fimasartan and those receiving other ARBs (candesartan, valsartan, losartan, telmisartan, olmesartan, and irbesartan). The primary outcome was a composite of all-cause death, recurrent MI, hospitalization for heart failure, and stroke. RESULTS Of 2,802 eligible patients, fimasartan was prescribed to 124 patients (4.4%). During a median follow-up of 2.2 years (interquartile range, 1.0-3.9), 613 events of the primary outcome occurred. There was no significant difference in the primary outcome between patients receiving fimasartan and those receiving other ARBs (adjusted hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.46-1.45). Compared with patients receiving other ARBs, those receiving fimasartan had comparable incidence of all-cause death (adjusted HR, 0.70; 95% CI, 0.30-1.63), recurrent MI (adjusted HR, 1.28; 95% CI, 0.49-3.34), hospitalization for heart failure (adjusted HR, 0.70; 95% CI, 0.27-1.84), and stroke (adjusted HR, 0.59; 95% CI, 0.18-1.96). CONCLUSION In this nationwide cohort, fimasartan, compared with other ARBs, had comparable treatment effects for a composite of all-cause death, recurrent MI, hospitalization for heart failure, and stroke in patients with heart failure after MI.
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Affiliation(s)
- Jihoon Kim
- Division of Cardiology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Danbee Kang
- Center for Clinical Epidemiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Sung Eun Kim
- Division of Cardiology, Inje University Ilsan Paik Hospital, Goyang, Korea
| | - Hyejeong Park
- Center for Clinical Epidemiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Taek Kyu Park
- Division of Cardiology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Joo Myung Lee
- Division of Cardiology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jeong Hoon Yang
- Division of Cardiology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Young Bin Song
- Division of Cardiology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jin-Ho Choi
- Division of Cardiology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Seung-Hyuk Choi
- Division of Cardiology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Hyeon-Cheol Gwon
- Division of Cardiology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Eliseo Guallar
- Center for Clinical Epidemiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Juhee Cho
- Center for Clinical Epidemiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
| | - Joo-Yong Hahn
- Division of Cardiology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
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Tong PCY, Chan SCP, Chan WB, Ho KKL, Leung GTC, Lo SHK, Mak GYK, Tse TS. Consensus Statements from the Diabetologists & Endocrinologists Alliance for the Management of People with Hypertension and Type 2 Diabetes Mellitus. J Clin Med 2023; 12:jcm12103403. [PMID: 37240509 DOI: 10.3390/jcm12103403] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2023] [Revised: 05/04/2023] [Accepted: 05/10/2023] [Indexed: 05/28/2023] Open
Abstract
Hypertension and type 2 diabetes mellitus (T2DM) are important, intertwined public health issues. People with both conditions face significantly elevated risks of cardiovascular (CV) and renal complications. To optimize patient care, a multidisciplinary expert panel met to review recent evidence on optimal blood pressure (BP) targets, implications of albuminuria, and treatment regimens for hypertensive patients with T2DM, with the aim of providing recommendations for physicians in Hong Kong. The panel reviewed the relevant literature, obtained by searching PubMed for the publication period from January 2015 to June 2021, to address five discussion areas: (i) BP targets based on CV/renal benefits; (ii) management of isolated systolic or diastolic hypertension; (iii) roles of angiotensin II receptor blockers; (iv) implications of albuminuria for CV/renal events and treatment choices; and (v) roles and tools of screening for microalbuminuria. The panel held three virtual meetings using a modified Delphi method to address the discussion areas. After each meeting, consensus statements were derived and anonymously voted on by every panelist. A total of 17 consensus statements were formulated based on recent evidence and expert insights regarding cardioprotection and renoprotection for hypertensive patients with T2DM.
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Affiliation(s)
| | | | - Wing-Bun Chan
- Diabetologists & Endocrinologists Alliance, Hong Kong SAR, China
| | | | | | | | | | - Tak-Sun Tse
- Diabetologists & Endocrinologists Alliance, Hong Kong SAR, China
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Haque SM, Kabir A, Rahman N, Azmi SNH. Response surface methodology combined Box-Behnken design optimized green kinetic spectrophotometric and HPLC methods to quantify angiotensin receptor blocker valsartan in pharmaceutical formulations. SPECTROCHIMICA ACTA. PART A, MOLECULAR AND BIOMOLECULAR SPECTROSCOPY 2023; 298:122805. [PMID: 37156177 DOI: 10.1016/j.saa.2023.122805] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/07/2023] [Revised: 04/07/2023] [Accepted: 04/26/2023] [Indexed: 05/10/2023]
Abstract
The high-performance liquid chromatographic (HPLC) and kinetic spectrophotometric methods were established to compute valsartan (VAL) in pharmaceutical formulations. The spectrophotometric procedures adopted initial rate, fixed time, and equilibrium strategies to assess VAL. The method was based on the carboxylic acid group of the oxidized VAL with a mixture of potassium iodate (KIO3) and potassium iodide (KI) at room temperature, producing a stable, yellow-coloured absorb at 352 nm. The critical parameters were optimized using green process optimization methodology such as Box-Behnken design (BBD) which belongs to response surface methodology (RSM). After the screening, experiments identified them as significant, and then three crucial factors were optimised: KI volume, KIO3 volume, and reaction time against response as absorbance. The HPLC procedure was also optimized based on the desirability function on RSM-BBD. The parameters such as pH, methanol (%), and flow rate (ml/min) were optimized with the best responses: peak area, symmetry, and theoretical plates. The linearity of spectrophotometric and HPLC methods was within the range of 2-24 and 0.25-11.25 µg/ml, respectively. The developed procedures produced excellent accuracy and precision. The design of the experiment (DoE) setting explained and discussed the individual steps and the importance of independent and dependent variables used to develop the model and optimization. The method was validated as per the International Conference on Harmonization (ICH) guidelines. Furthermore, Youden's robustness study was applied with factorial combinations of the preferred analytical parameters and explored their influence with alternative conditions. The analytical Eco-Scale score was calculated and was found a better option as green methods to quantify VAL. The results were reproducible with the analysis completed with biological fluid and wastewater samples.
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Affiliation(s)
- Sk Manirul Haque
- Industrial Chemistry Division, Department of Chemical Engineering, Jubail Industrial College, Jubail Industrial City, P.O. Box No-10099, Saudi Arabia.
| | - Abuzar Kabir
- International Forensic Research Institute, Department of Chemistry and Biochemistry, Florida International University, Miami, FL 33131, USA
| | - Nafisur Rahman
- Department of Chemistry, Aligarh Muslim University, Aligarh 202002, Uttar Pradesh, India
| | - Syed Najmul Hejaz Azmi
- Department of Applied Sciences, College of Applied Sciences and Pharmacy, University of Technology and Applied Sciences-Muscat, P.O. Box 74, Al-Khuwair 133, Sultanate of Oman
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Swiderski J, Gadanec LK, Apostolopoulos V, Moore GJ, Kelaidonis K, Matsoukas JM, Zulli A. Role of Angiotensin II in Cardiovascular Diseases: Introducing Bisartans as a Novel Therapy for Coronavirus 2019. Biomolecules 2023; 13:787. [PMID: 37238657 PMCID: PMC10216788 DOI: 10.3390/biom13050787] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2023] [Revised: 04/26/2023] [Accepted: 04/27/2023] [Indexed: 05/28/2023] Open
Abstract
Cardiovascular diseases (CVDs) are the main contributors to global morbidity and mortality. Major pathogenic phenotypes of CVDs include the development of endothelial dysfunction, oxidative stress, and hyper-inflammatory responses. These phenotypes have been found to overlap with the pathophysiological complications of coronavirus disease 2019 (COVID-19). CVDs have been identified as major risk factors for severe and fatal COVID-19 states. The renin-angiotensin system (RAS) is an important regulatory system in cardiovascular homeostasis. However, its dysregulation is observed in CVDs, where upregulation of angiotensin type 1 receptor (AT1R) signaling via angiotensin II (AngII) leads to the AngII-dependent pathogenic development of CVDs. Additionally, the interaction between the spike protein of severe acute respiratory syndrome coronavirus 2 with angiotensin-converting enzyme 2 leads to the downregulation of the latter, resulting in the dysregulation of the RAS. This dysregulation favors AngII/AT1R toxic signaling pathways, providing a mechanical link between cardiovascular pathology and COVID-19. Therefore, inhibiting AngII/AT1R signaling through angiotensin receptor blockers (ARBs) has been indicated as a promising therapeutic approach to the treatment of COVID-19. Herein, we review the role of AngII in CVDs and its upregulation in COVID-19. We also provide a future direction for the potential implication of a novel class of ARBs called bisartans, which are speculated to contain multifunctional targeting towards COVID-19.
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Affiliation(s)
- Jordan Swiderski
- Institute for Health and Sport, Victoria University, Melbourne, VIC 3030, Australia; (J.S.); (L.K.G.); (V.A.)
| | - Laura Kate Gadanec
- Institute for Health and Sport, Victoria University, Melbourne, VIC 3030, Australia; (J.S.); (L.K.G.); (V.A.)
| | - Vasso Apostolopoulos
- Institute for Health and Sport, Victoria University, Melbourne, VIC 3030, Australia; (J.S.); (L.K.G.); (V.A.)
- Immunology Program, Australian Institute for Musculoskeletal Science, Melbourne, VIC 3021, Australia
| | - Graham J. Moore
- Pepmetics Incorporated, 772 Murphy Place, Victoria, BC V8Y 3H4, Canada;
- Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada
| | | | - John M. Matsoukas
- Institute for Health and Sport, Victoria University, Melbourne, VIC 3030, Australia; (J.S.); (L.K.G.); (V.A.)
- Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada
- NewDrug PC, Patras Science Park, 26500 Patras, Greece;
- Department of Chemistry, University of Patras, 26504 Patras, Greece
| | - Anthony Zulli
- Institute for Health and Sport, Victoria University, Melbourne, VIC 3030, Australia; (J.S.); (L.K.G.); (V.A.)
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Zhang P, Hou Y, Tu W, Campbell N, Pieper AA, Leverenz JB, Gao S, Cummings J, Cheng F. Population-based discovery and Mendelian randomization analysis identify telmisartan as a candidate medicine for Alzheimer's disease in African Americans. Alzheimers Dement 2023; 19:1876-1887. [PMID: 36331056 PMCID: PMC10156891 DOI: 10.1002/alz.12819] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2022] [Revised: 08/11/2022] [Accepted: 09/02/2022] [Indexed: 11/06/2022]
Abstract
INTRODUCTION African Americans (AAs) and European Americans (EAs) differ in Alzheimer's disease (AD) prevalence, risk factors, and symptomatic presentation and AAs are less likely to enroll in AD clinical trials. METHODS We conducted race-conscious pharmacoepidemiologic studies of 5.62 million older individuals (age ≥60) to investigate the association of telmisartan exposure and AD outcome using Cox analysis, Kaplan-Meier analysis, and log-rank test. We performed Mendelian randomization (MR) analysis of large ethnically diverse genetic data to test likely causal relationships between telmisartan's target and AD. RESULTS We identified that moderate/high telmisartan exposure was significantly associated with a reduced incidence of AD in the AAs compared to low/no telmisartan exposure (hazard ratio [HR] = 0.77, 95% CI: 0.65-0.91, p-value = 0.0022), but not in the non-Hispanic EAs (HR = 0.97, 95% CI: 0.89-1.05, p-value = 0.4110). Sensitivity and sex-/age-stratified patient subgroup analyses identified that telmisartan's medication possession ratio (MPR) and average hypertension daily dosage were significantly associated with a stronger reduction in the incidence of both AD and dementia in AAs. Using MR analysis from large genome-wide association studies (GWAS) (over 2 million individuals) across AD, hypertension, and diabetes, we further identified AA-specific beneficial effects of telmisartan for AD. DISCUSSION Randomized controlled trials with ethnically diverse patient cohorts are warranted to establish causality and therapeutic outcomes of telmisartan and AD. HIGHLIGHTS Telmisartan is associated with lower risk of Alzheimer's disease (AD) in African Americans (AAs). Telmisartan is the only angiotensin II receptor blockers having PPAR-γ agonistic properties with beneficial anti-diabetic and renal function effects, which mitigate AD risk in AAs. Mendelian randomization (MR) analysis demonstrates the specificity of telmisartan's protective mechanism to AAs.
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Affiliation(s)
- Pengyue Zhang
- Department of Biostatistics and Health Data Science, Indiana University, Indianapolis, Indiana, USA
| | - Yuan Hou
- Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA
| | - Wanzhu Tu
- Department of Biostatistics and Health Data Science, Indiana University, Indianapolis, Indiana, USA
| | - Noll Campbell
- Department of Pharmacy Practice, Purdue University, West Lafayette, Indiana, USA
| | - Andrew A. Pieper
- Harrington Discovery Institute, University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA
- Department of Psychiatry, Case Western Reserve University, Cleveland, Ohio, USA
- Geriatric Psychiatry, GRECC, Louis Stokes Cleveland VA Medical Center, Cleveland, Ohio, USA
- Institute for Transformative Molecular Medicine, School of Medicine, Case Western Reserve University, Cleveland, Ohio, USA
- Department of Neuroscience, Case Western Reserve University, School of Medicine, Cleveland, Ohio, USA
| | - James B. Leverenz
- Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, Ohio, USA
- Lou Ruvo Center for Brain Health, Neurological Institute, Cleveland Clinic, Cleveland, Ohio, USA
| | - Sujuan Gao
- Department of Biostatistics and Health Data Science, Indiana University, Indianapolis, Indiana, USA
| | - Jeffrey Cummings
- Chambers-Grundy Center for Transformative Neuroscience, Department of Brain Health, School of Integrated Health Sciences, University of Nevada Las Vegas, Las Vegas, Nevada, USA
| | - Feixiong Cheng
- Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA
- Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, Ohio, USA
- Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA
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Lee S, Kim H, Woo Yim H, Hun-Sung K, Han Kim J. Comparison of cardiocerebrovascular disease incidence between angiotensin converting enzyme inhibitor and angiotensin receptor blocker users in a real-world cohort. J Appl Biomed 2023; 21:7-14. [PMID: 37016775 DOI: 10.32725/jab.2023.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2022] [Accepted: 03/22/2023] [Indexed: 03/29/2023] Open
Abstract
BACKGROUND Both angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) are known to be effective in managing cardiovascular diseases, but more evidence supports the use of an ACEI. This study investigated the difference in cardiovascular disease incidence between relatively low-compliance ACEIs and high-compliance ARBs in the clinical setting. METHODS Patients who were first prescribed ACEIs or ARBs at two tertiary university hospitals in Korea were observed in this retrospective cohort study for the incidence of heart failure, angina, acute myocardial infarction, cerebrovascular disease, ischemic heart disease, and major adverse cardiovascular events for 5 years after the first prescription. Additionally, 5-year Kaplan-Meier survival curves were used based on the presence or absence of statins. RESULTS Overall, 2,945 and 9,189 patients were prescribed ACEIs and ARBs, respectively. When compared to ACEIs, the incidence of heart failure decreased by 52% in those taking ARBs (HR [95% CI] = 0.48 [0.39-0.60], P < 0.001), and the incidence of cerebrovascular disease increased by 62% (HR [95% CI] = 1.62 [1.26-2.07], P < 0.001). The incidence of ischemic heart disease (P = 0.223) and major adverse cardiovascular events (P = 0.374) did not differ significantly between the two groups. CONCLUSIONS ARBs were not inferior to ACEIs in relation to reducing the incidence of cardiocerebrovascular disease in the clinical setting; however, there were slight differences for each disease. The greatest strength of real-world evidence is that it allows the follow-up of specific drug use, including drug compliance. Large-scale studies on the effects of relatively low-compliance ACEIs and high-compliance ARBs on cardiocerebrovascular disease are warranted in the future.
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Oh H, Kim KY, Yoo DW, Yoon IM. Blood Pressure-Lowering Effect of Fimasartan Versus Comparators: A Cross-Inference With a Systematic Review and Meta-Analysis Through a Quality Management System. Clin Ther 2023:S0149-2918(23)00025-5. [PMID: 36925383 DOI: 10.1016/j.clinthera.2023.01.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2022] [Revised: 12/09/2022] [Accepted: 01/05/2023] [Indexed: 03/18/2023]
Abstract
PURPOSE Fimasartan, one of the newest angiotensin receptor blockers (ARBs) available worldwide, has been investigated extensively since its initial development. Our study group conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating fimasartan and comparators for their blood pressure (BP)-lowering effect. Moreover, we employed a cross-inference (frequentist and Bayesian inference) system, which has never been used in the medical field, to confirm the results of our study. In addition, a quality management system was integrated throughout the study for data quality. METHODS PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, ClinicalKey, and ClinicalTrial.gov were searched for RCT studies from March 1998 to March 2022. In each study, the mean differences (MDs) and 95% CIs were identified for reductions in clinic sitting systolic and diastolic BP (SiSBP/SiDBP) or 24-hour mean systolic BP and diastolic BP by ambulatory BP monitoring (ASBP/ADBP) from baseline between the fimasartan and comparator groups, followed by meta-analysis. A subsequent meta-analysis was performed with frequentist and Bayesian inference as a tool in the cross-checking system. FINDINGS Eleven RCTs with a total of 2459 subjects were included in the study. The clinic SiSBP/SiDBP-lowering effect of fimasartan was significantly greater relative to those of comparators (MD for clinic SiSBP, -2.58 mm Hg [95% CI, -4.35 to -0.81; P = 0.004]; MD for clinic SiDBP, -2.13 mm Hg [95% CI, -2.96 to -1.30; P = 0.00001]). The ASBP/ADBP-lowering effect of fimasartan was also significantly greater relative to those of comparators (MD for ASBP, -3.58 mm Hg [95% CI, -5.74 to -1.43; P = 0.001]; MD for ADBP, -1.99 mm Hg [95% CI, -3.34 to -0.63; P = 0.004]). IMPLICATIONS Fimasartan seems to be more effective in lowering BP than its comparators, including other ARBs. Although there is a limited amount of data and a minuscule number of study subjects available, the results of cross-inference (frequentist + Bayesian) were fairly consistent with the meta-analysis results through our quality management system.
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Affiliation(s)
- Hojin Oh
- Oh Medicine and Methodology Research Institute, Seoryeong-ro, Seosan, Chungcheongnam-do, Republic of Korea; Chung-Ang Herb Dental Clinic, Seosan, Chungcheongnam-do, Republic of Korea.
| | - Kang-Yeon Kim
- Yonsei Da-on Family Medicine Clinic, Seosan, Chungcheongnam-do, Republic of Korea
| | - Duk-Woo Yoo
- Chung-Ang Herb Dental Clinic, Seosan, Chungcheongnam-do, Republic of Korea
| | - In Mo Yoon
- Unimedi Plastic Surgery Clinic, Gangnam-gu, Seoul, Republic of Korea
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de Carvalho WC, de Sousa TL, de Jesus ACL, Souza LA, Dos Santos LC, da Silva SVS, Santos DCMB, de Freitas Santos Júnior A, Korn MDGA. Effect of losartan potassium, metformin hydrochloride, and simvastatin on in vitro bioaccessibility of Cu, Fe, Mn, and Zn in oat flour from Brazil. J Trace Elem Med Biol 2022; 73:127032. [PMID: 35797925 DOI: 10.1016/j.jtemb.2022.127032] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2022] [Revised: 06/23/2022] [Accepted: 06/29/2022] [Indexed: 10/17/2022]
Abstract
BACKGROUND The simultaneous administration of drugs with food can compromise the bioaccessibility and absorption of nutrients. The objective of this study was to evaluate the influence of the use of losartan potassium (LP), metformin hydrochloride (MH), and simvastatin (S) on the in vitro bioaccessibility of micronutrients (Cu, Fe, Mn, and Zn) in oat flour from Bahia, Brazil. METHODS The experimental procedure consisted of the in vitro extraction of the bioaccessible fraction of Cu, Fe, Mn, and Zn in oat flour-with and without LP (50 mg), MH (500 mg), and S (20 mg)-using the unified bioaccessibility method (UBM), simulating the conditions of the gastrointestinal tract. For decomposition of the samples (oat flour and residue), a digester block with a closed system was used. To determine the total content (flour and residual fraction) and bioaccessible micronutrients, inductively coupled plasma optical emission spectrometry (ICP OES) was used. RESULTS The bioaccessible contents (µg g-1) without the addition of drugs were: Cu 5.86 ± 0.21, Fe 32.80 ± 1.32, Mn 87.90 ± 1.90, and Zn 30.33 ± 2.05, with bioaccessibility ranging from 31.5 % for Fe to 99 % for Mn. The in vitro extraction method was validated by mass balance with recovery values from 89.78 % for Cu to 101.94 % for Mn. The range of bioaccessible contents (µg g-1) were: Cu (<4.14), Fe (32.10 ± 0.20-54.10 ± 2.03), Mn (81.40 ± 0.93-93.22 ± 0.80), and Zn (<10.80-29.11 ± 2.20). The estimation of the bioaccessibility of Cu, Mn, and Zn in oat flour were compromised in the presence of LP, MH, and S (p < 0.05). CONCLUSION Chemical interactions can occur between drugs and micronutrients. Taken together, our results highlight that LP, MH, and S can interfere with the bioaccessibility of Cu, Fe, Mn, and Zn in oat flour in patients who use these drugs, suggesting its rational use in further investigations.
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Affiliation(s)
- Wellington Correia de Carvalho
- Chemistry Institute, Universidade Federal da Bahia, Salvador, Bahia 40170-115, Brazil; Instituto Federal de Educação, Ciência e Tecnologia da Bahia (IFBA), Campus Porto Seguro, Porto Seguro, Bahia 45810-000, Brazil
| | - Thaís Luz de Sousa
- Chemistry Institute, Universidade Federal da Bahia, Salvador, Bahia 40170-115, Brazil
| | | | - Laís Araújo Souza
- Chemistry Institute, Universidade Federal da Bahia, Salvador, Bahia 40170-115, Brazil
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Gallo G, Volpe M, Rubattu S. Angiotensin Receptor Blockers in the Management of Hypertension: A Real-World Perspective and Current Recommendations. Vasc Health Risk Manag 2022; 18:507-515. [PMID: 35846737 PMCID: PMC9285525 DOI: 10.2147/vhrm.s337640] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2022] [Accepted: 07/07/2022] [Indexed: 12/13/2022] Open
Abstract
Hypertension represents a major common cardiovascular risk factor. Optimal control of high blood pressure levels is recommended to reduce the global burden of hypertensive-mediated organ damage and cardiovascular (CV) events. Among the first-line drugs recommended in international guidelines, renin-angiotensin-aldosterone system antagonists [angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs)] have long represented a rational, effective, and safe anti-hypertensive pharmacological strategy. In fact, current US and European guidelines recommend ACEi and ARBs as a suitable first choice for hypertension treatment together with calcium channel blockers (CCBs) and thiazide diuretics. Different studies have demonstrated that ARBs and ACEi exert a comparable effect in lowering blood pressure levels. However, ARBs are characterized by better pharmacological tolerability. Most importantly, the clinical evidence supports a relevant protective role of ARBs toward the CV and renal damage development, as well as the occurrence of major adverse CV events, in hypertensive patients. Moreover, a neutral metabolic effect has been reported upon ARBs administration, in contrast to other antihypertensive agents, such as beta-blockers and diuretics. These properties highlight the use of ARBs as an excellent pharmacological strategy to manage hypertension and its dangerous consequences. The present review article summarizes the available evidence regarding the beneficial effects and current recommendations of ARBs in hypertension. The specific properties performed by these agents in various clinical subsets are discussed, also including an overview of their implications for the current COVID-19 pandemic.
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Affiliation(s)
- Giovanna Gallo
- Department of Clinical and Molecular Medicine, Sapienza University of Rome, Sant'Andrea Hospital, Rome, Italy
| | - Massimo Volpe
- Department of Clinical and Molecular Medicine, Sapienza University of Rome, Sant'Andrea Hospital, Rome, Italy
| | - Speranza Rubattu
- Department of Clinical and Molecular Medicine, Sapienza University of Rome, Sant'Andrea Hospital, Rome, Italy.,IRCCS Neuromed, Pozzilli, IS, Italy
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Yang XF, Wang H, Huang Y, Huang JH, Ren HL, Xu Q, Su XM, Wang AM, Ren F, Zhou MS. Myeloid Angiotensin II Type 1 Receptor Mediates Macrophage Polarization and Promotes Vascular Injury in DOCA/Salt Hypertensive Mice. Front Pharmacol 2022; 13:879693. [PMID: 35721173 PMCID: PMC9204513 DOI: 10.3389/fphar.2022.879693] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2022] [Accepted: 04/19/2022] [Indexed: 11/22/2022] Open
Abstract
Activation of the renin–angiotensin system has been implicated in hypertension. Angiotensin (Ang) II is a potent proinflammatory mediator. The present study investigated the role of myeloid angiotensin type 1 receptor (AT1R) in control of macrophage phenotype in vitro and vascular injury in deoxycorticosterone acetate (DOCA)/salt hypertension. In human THP-1/macrophages, Ang II increased mRNA expressions of M1 cytokines and decreased M2 cytokine expressions. Overexpression of AT1R further increased Ang II-induced expressions of M1 cytokines and decreased M2 cytokines. Silenced AT1R reversed Ang II-induced changes in M1 and M2 cytokines. Ang II upregulated hypoxia-inducible factor (HIF)1α, toll-like receptor (TLR)4, and the ratio of pIκB/IκB, which were prevented by silenced AT1R. Silenced HIF1α prevented Ang II activation of the TLR4/NFκB pathway. Furthermore, Ang II increased HIF1α via reactive oxygen species-dependent reduction in prolyl hydroxylase domain protein 2 (PHD2) expression. The expressions of AT1R and HIF1α and the ratio of pIκB/IκB were upregulated in the peritoneal macrophages of DOCA hypertensive mice, and the specific deletion of myeloid AT1R attenuated cardiac and vascular injury and vascular oxidative stress, reduced the recruitment of macrophages and M1 cytokine expressions, and improved endothelial function without significant reduction in blood pressure. Our results demonstrate that Ang II/AT1R controls the macrophage phenotype via stimulating the HIF1α/NFκB pathway, and specific myeloid AT1R KO improves endothelial function, vascular inflammation, and injury in salt-sensitive hypertension. The results support the notion that myeloid AT1R plays an important role in the regulation of the macrophage phenotype, and dysfunction of this receptor may promote vascular dysfunction and injury in salt-sensitive hypertension.
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Affiliation(s)
- Xue-Feng Yang
- Department of Physiology, Jinzhou Medical University, Jinzhou, China
| | - Huan Wang
- Department of Physiology, Shenyang Medical College, Shenyang, China
| | - Yue Huang
- The First Affiliated Hospital, Jinzhou Medical University, Jinzhou, China
| | - Jian-Hua Huang
- The First Affiliated Hospital, Jinzhou Medical University, Jinzhou, China
| | - Hao-Lin Ren
- Radiology Department of the First Affiliated Hospital, Dalian Medical University, Dalian, China
| | - Qian Xu
- Department of Physiology, Shenyang Medical College, Shenyang, China
| | - Xiao-Min Su
- Department of Physiology, Shenyang Medical College, Shenyang, China
| | - Ai-Mei Wang
- Department of Physiology, Jinzhou Medical University, Jinzhou, China
| | - Fu Ren
- Department of Anatomy, Shenyang Medical College, Shenyang, China
- *Correspondence: Ming-Sheng Zhou, ; Fu Ren,
| | - Ming-Sheng Zhou
- Department of Physiology, Shenyang Medical College, Shenyang, China
- *Correspondence: Ming-Sheng Zhou, ; Fu Ren,
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Fooladi M, Cheki M, Shirazi A, Sheikhzadeh P, Amirrashedi M, Ghahramani F, Khoobi M. Histopathological Evaluation of Protective Effect of Telmisartan against Radiation-Induced Bone Marrow Injury. J Biomed Phys Eng 2022; 12:277-284. [PMID: 35698535 PMCID: PMC9175127 DOI: 10.31661/jbpe.v0i0.2012-1243] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2020] [Accepted: 01/20/2021] [Indexed: 06/15/2023]
Abstract
BACKGROUND Radiation-induced hematopoietic suppression and myelotoxicity can occur due to the nuclear accidents, occupational irradiation and therapeutic interventions. Bone marrow dysfunction has always been one of the most important causes of morbidity and mortality after ionizing irradiation. OBJECTIVE This study aims to investigate the protective effect of telmisartan against radiation-induced bone marrow injuries in a Balb/c mouse model. MATERIAL AND METHODS In this experimental study, male Balb/c mice were divided into four groups as follow: group 1: mice received phosphate buffered saline (PBS) without irradiation, group 2: mice received a solution of telmisartan in PBS without irradiation, group 3: mice received PBS with irradiation, and group 4: mice received a solution of telmisartan in PBS with irradiation. A solution of telmisartan was prepared and administered orally at 12 mg/kg body weight for seven consecutive days prior to whole body exposing to a single sub-lethal dose of 5 Gy X-rays. Protection of bone marrow against radiation induced damage was investigated by Hematoxylin-Eosin (HE) staining assay at 3, 9, 15 and 30 days after irradiation. RESULTS Histopathological analysis indicated that administration of telmisartan reduced X-radiation-induced damage and improved bone marrow histology. The number of different cell types in bone marrow, including polymorphonuclear /mononuclear cells and megakaryocytes significantly increased in telmisartan treated group compared to the only irradiated group at all-time points. CONCLUSION The results of the present study demonstrated an efficient radioprotective effect of telmisartan in mouse bone marrow against sub-lethal X-irradiation.
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Affiliation(s)
- Masoomeh Fooladi
- PhD Candidate, Department of Medical Physics and Biomedical Engineering, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohsen Cheki
- PhD, Department of Medical Imaging and Radiation Sciences, Faculty of Paramedicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Alireza Shirazi
- PhD Candidate, Department of Medical Physics and Biomedical Engineering, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Peyman Sheikhzadeh
- PhD, Department of Nuclear Medicine, Imam khomeini Hospital complex, Tehran University of Medical Sciences, Tehran, Iran
| | - Mahsa Amirrashedi
- PhD Candidate, Department of Medical Physics and Biomedical Engineering, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
- PhD Candidate, Research Center for Molecular and Cellular Imaging, Tehran University of Medical Sciences, Tehran, Iran
| | - Fatemeh Ghahramani
- MSc, Radiotherapy-Oncology Center, Yas Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Mehdi Khoobi
- PhD, Biomaterials Group, Pharmaceutical Sciences Research Center, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran
- PhD, Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
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Barroso WKS, Brandão AA, Vitorino PVDO, Feitosa ADDM, Barbosa ECD, Miranda RD, Redon J, Camafort-Babkowski M, Coca A, Gomes MAM. Angiotensin Receptor Blockers Evaluated by Office and Home Blood Pressure Measurements. TeleHBPM Study. Arq Bras Cardiol 2022; 118:S0066-782X2022005005204. [PMID: 35544853 PMCID: PMC9345159 DOI: 10.36660/abc.20210504] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2021] [Revised: 08/08/2021] [Accepted: 09/01/2021] [Indexed: 11/23/2022] Open
Abstract
BACKGROUND Adequate treatment of arterial hypertension and achieving arterial hypertension goals in are important in reducing cardiovascular outcomes. OBJECTIVES To describe angiotensin receptor blockers in monotherapy or double combination therapy and the rate of arterial hypertension control. METHODS This cross-sectional study evaluated patients who were using angiotensin receptor blockers between 2017 and 2020. Those using three or more antihypertensive drugs were excluded. The analyzed variables included sex, age, body mass index, valid home blood pressure monitoring (HBPM) measurements, casual and HBPM systolic and diastolic blood pressure measurements, blood pressure variability, and antihypertensive and angiotensin receptor blocker class. Paired t, chi-square, and Fisher's exact tests were used, as well as overlapping 95% confidence intervals and a significance level of 5% (p < 0.05). RESULTS Of 17,013 patients, 12,813 met the inclusion criteria, 62.1% of whom were female. The mean number of valid measurements was 23.3 (SD, 2.0). The mean HBPM and casual measurements for systolic blood pressure were 126.8 (SD, 15.8) mmHg and 133.5 (SD, 20.1) mmHg (p <0.001), respectively, while those for diastolic blood pressure were 79.1 (SD, 9.7 mmHg) and 83.6 (SD, 11.9) mmHg (p <0.001), respectively. Losartan was the most common angiotensin receptor blocker and resulted in the highest blood pressure values. Combinations of angiotensin receptor blockers with diuretics or calcium channel antagonists resulted in lower blood pressure values. CONCLUSIONS More than half of the patients used losartan, although it was the least efficient drug for reducing and controlling blood pressure.
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Affiliation(s)
- Weimar Kunz Sebba Barroso
- Universidade Federal de GoiásLiga de Hipertensão ArterialGoiâniaGOBrasilUniversidade Federal de Goiás - Liga de Hipertensão Arterial, Goiânia, GO – Brasil
| | - Andréa Araujo Brandão
- Universidade do Estado do Rio de JaneiroRio de JaneiroRJBrasilUniversidade do Estado do Rio de Janeiro – Cardiologia, Rio de Janeiro, RJ – Brasil
| | - Priscila Valverde de Oliveira Vitorino
- Pontifícia Universidade Católica de GoiásEscola de Ciências Sociais e da SaúdeGoiâniaGOBrasilPontifícia Universidade Católica de Goiás - Escola de Ciências Sociais e da Saúde,Goiânia, GO – Brasil
| | - Audes Diógenes de Magalhães Feitosa
- Universidade de PernambucoRecifePEBrasilUniversidade de Pernambuco, Recife, PE – Brasil
- Universidade Católica de PernambucoRecifePEBrasilUniversidade Católica de Pernambuco, Recife, PE – Brasil
| | - Eduardo Costa Duarte Barbosa
- Complexo Hospitalar Santa Casa de Misericórdia de Porto AlegrePorto AlegreRSBrasilComplexo Hospitalar Santa Casa de Misericórdia de Porto Alegre – Cardiologia, Porto Alegre, RS - Brasil
| | - Roberto Dischinger Miranda
- Universidade Federal de São PauloEscola Paulista de MedicinaSão PauloSPBrasilUniversidade Federal de São Paulo - Escola Paulista de Medicina, São Paulo, SP – Brasil
| | - Josep Redon
- University of ValenciaValenciaEspanhaUniversity of Valencia – Hypertension, Valencia, Comunitat Valenciana – Espanha
| | - Miguel Camafort-Babkowski
- University of BarcelonaHospital ClínicHypertension UnitBarcelonaCatalunyaEspanhaUniversity of Barcelona - Hospital Clínic. Hypertension Unit, Barcelona, Catalunya – Espanha
| | - Antonio Coca
- Hypertension and Vascular Risk UnitHospital ClinicUniversity of BarcelonaBarcelonaEspanhaHypertension and Vascular Risk Unit. Hospital Clinic. University of Barcelona,Barcelona – Espanha
| | - Marco Antônio Mota Gomes
- Centro Universitário CESMACHospital do CoraçãoMaceióALBrasilCentro Universitário CESMAC - Hospital do Coração, Maceió, AL – Brasil
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Synthesis and evaluation of new sartan derivatives. Med Chem Res 2022. [DOI: 10.1007/s00044-022-02877-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
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40
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Munjal A, Khandia R, Paladhi S, Pandey M, Parihar A, Pathe C, Rajukumar K, Bin Emran T, Alqahtani T, Alqahtani AM, Alamri AH, Chidambara K, Dhama K. Evaluating the Effects of Hypotensive Drug Valsartan on Angiogenesis and Associated Breast Ductal Carcinoma Cell Metastasis. INT J PHARMACOL 2022. [DOI: 10.3923/ijp.2022.817.825] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
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Devan AR, Nair B, Kumar AR, Nath LR. An insight into the role of telmisartan as PPAR-γ/α dual activator in the management of nonalcoholic fatty liver disease. Biotechnol Appl Biochem 2022; 69:461-468. [PMID: 33578449 DOI: 10.1002/bab.2123] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2020] [Accepted: 02/07/2021] [Indexed: 02/05/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the most common hepatic disease. It is rapidly emerging as the frequent cause for liver transplantation with the risk of disease recurrence, even after transplantation. Clinical evidence showed an abnormally altered expression of different peroxisome proliferator-activated receptor (PPAR) isotypes (PPAR-α/γ/δ) in NAFLD with an involvement in the induction of insulin resistance, hepatic steatosis, reactive oxygen species (ROS) formation, and hepatic inflammation. Recently, several dual PPAR-γ/α agonists were developed to simultaneously achieve the insulin-sensitizing effect of PPAR-γ as well as lipid catabolizing effect of PPAR-α. PPAR-α activation could counterbalance the steatogenic and adipogenic effects of PPAR-γ. But most of the drugs were ended in the initial level itself due to harmful adverse effects. In the present review, we discuss the possible mechanism of telmisartan, a typical angiotensin receptor blocker with excellent safety and pharmacokinetic profile, as a PPAR-γ/α dual agonist in the treatment of NAFLD.
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Affiliation(s)
- Aswathy R Devan
- Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Science Campus, Kochi, Kerala, India
| | - Bhagyalakshmi Nair
- Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Science Campus, Kochi, Kerala, India
| | - Ayana R Kumar
- Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Science Campus, Kochi, Kerala, India
| | - Lekshmi R Nath
- Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Science Campus, Kochi, Kerala, India
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Abstract
Tremendous efforts are being made around the world to develop efficient ways to prevent/treat the novel β-coronavirus disease (COVID-19) caused by SARS-CoV-2. There are currently many studies and clinical trials (either based on computational predictions or clinical experiences), in progress, focusing on finding relevant protein targets and medications anti-COVID-19. In the present study, we report a hydrogel drug delivery system based on Laponite® RD (Lap) entrapped in a poly(vinyl alcohol) (PVA) matrix obtained by freezing/thawing method. The PVA/Lap hydrogels were characterized in terms of their morphological, rheological, and swelling properties. Moreover, in vitro drug delivery investigations were performed with a promising drug, Rifampicin (Rif). Rif is an antitubercular drug and was selected for this study in order to demonstrate its efficacy as an anti-COVID-19 repurposed drug. In vitro studies were supplemented by in silico molecular docking simulations of Rif capacity of inhibition against SARS-CoV-2 target protein 3-chymotrypsin-like protease (3CLpro). The results obtained in this study are encouraging and we propose the Rif loaded PVA/Lap hydrogels as promising drug delivery systems for COVID-19 treatment, promoting a synergistic therapeutic effect by dual targeting of viral 3CLpro and S proteins.
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Design and rationale for a comparison study of Olmesartan and Valsartan On myocardial metabolism In patients with Dilated cardiomyopathy (OVOID) trial: study protocol for a randomized controlled trial. Trials 2022; 23:36. [PMID: 35033178 PMCID: PMC8760768 DOI: 10.1186/s13063-021-05970-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2020] [Accepted: 12/23/2021] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Dilated cardiomyopathy (DCMP) is characterized by ventricular chamber enlargement and systolic dysfunction which may cause heart failure. Patients with DCMP have overactivation of the renin-angiotensin-aldosterone systems, which can also adversely affect myocardial metabolism in heart failure. The impairment of myocardial metabolism can contribute to the progression of left ventricular remodeling and contractile dysfunction in heart failure. Although angiotensin II receptor blockers (ARBs) have been used to treat patients with DCMP, there has been no direct comparison of the efficacy of these agents. The objective of this study is to compare the effects of olmesartan and valsartan on myocardial metabolism in patients with DCMP. METHODS/DESIGN The OVOID study (a comparison study of Olmesartan and Valsartan On myocardial metabolism In patients with Dilated cardiomyopathy) is designed as a non-blinded, open-label, parallel-group, prospective, randomized, controlled, multicenter clinical trial. A total of 40 DCMP patients aged between 20 and 85 years will be randomly allocated into the olmesartan or the valsartan group. 18F-fluoro-2-deoxyglucose (FDG) cardiac positron emission tomography (PET) will be performed at baseline and six months after receiving the study agent. The primary endpoint is myocardial glucose consumption per square meter, measured using 18F-FDG PET 6 months after receiving the study agent. DISCUSSION The purpose of this trial is to compare the efficacy between olmesartan and valsartan in improving myocardial metabolism in DCMP patients. This will be the first randomized comparative study investigating the differential effects of ARBs on heart failure. TRIAL REGISTRATION ClinicalTrials.gov NCT04174456 . Registered on 18 November 2019.
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Clinical characteristics of two groups commonly referred to an Irish hypertension service-patients with resistant hypertension and young adults with hypertension. Ir J Med Sci 2022; 191:2549-2557. [PMID: 35000115 DOI: 10.1007/s11845-021-02870-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2021] [Accepted: 11/24/2021] [Indexed: 10/19/2022]
Abstract
BACKGROUND The management of hypertension is primarily performed in primary care settings in many health systems. However, two groups of patients often require specialist input: patients with resistant hypertension (RH) and young adults with hypertension. AIMS To elucidate these groups by examining the characteristics of patients attending an Irish hypertension service, thus informing future management of hypertension. METHODS Patients were recruited at consecutive hypertension clinics at St James Hospital, Dublin from July to September 2019. Following patient consent, patient data were recorded to identify patient characteristics as well as the results of investigations, blood pressure (BP) measurements and the anti-hypertensive treatment of the study participants which were then analysed. RESULTS Two hundred thirty-six patients were included in the study. Compared to those without RH, the RH group were more likely to be obese (OR 2.59 [95% CI 1.06 to 6.33]), to have cardiovascular disease (OR 3.07 [95% CI 1.56 to 6.02]) and to have a non-dipping BP pattern (OR 3.86 [95% CI 1.57 to 9.47]). Young adults comprised 27% of the cohort. Forty-seven percent of these patients were obese, 15.9% had hypertension in pregnancy and 22.2% had chronic headaches. Despite being prescribed less anti-hypertensives (1.41 vs 2.28; p < 0.05), the majority of young patients had a BP less than 140/90 mmHg, comparing favourably with older patients (OR 2.25 [95% CI 1.20 to 4.27]). CONCLUSION This contemporary study highlights the high prevalence of obesity among RH patients and young adults with hypertension. Findings suggest that programs to combat hypertension must include interventions to address obesity.
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Soe HMSH, Sripetch S, Loftsson T, Stefánsson E, Jansook P. Effect of Soluplus ® on γ-cyclodextrin solubilization of irbesartan and candesartan and their nanoaggregates formation. Pharm Dev Technol 2021; 27:9-18. [PMID: 34895036 DOI: 10.1080/10837450.2021.2017968] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
The poor aqueous solubility of irbesartan (IRB) and candesartan cilexetil (CAC) may hamper their bioavailability when orally or topically administered. Among several attempts, the promising nanoaggregate formation by γ-cyclodextrin (γCD) complexation of drugs in aqueous solution with or without water-soluble polymers was investigated. According to phase solubility studies, Soluplus® showed the highest complexation efficiency (CE) of drug/γCD complexes among the polymers tested. The aqueous solubility of IRB and CAC was markedly increased as a function of Soluplus® concentrations. The binary drug/γCD and ternary drug/γCD/Soluplus® complex formations were supported and confirmed by solid-state characterizations, including differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and Fourier transform infrared (FT-IR) spectroscopy. The true inclusion mode was also proved by proton nuclear magnetic resonance (1H-NMR) spectroscopy. The nanoaggregate size and morphology of binary and ternary systems were observed using dynamic light scattering (DLS), and transmission electron microscopy (TEM) techniques. The size of these nanocarriers depends on the concentration of Soluplus®. The use of Soluplus® could significantly enhance drug solubility and stabilize complex nanoaggregates, which could be a prospective platform for drug delivery systems.
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Affiliation(s)
| | - Suppakan Sripetch
- Faculty of Pharmaceutical Sciences, University of Iceland, Reykjavik, Iceland
| | - Thorsteinn Loftsson
- Faculty of Pharmaceutical Sciences, University of Iceland, Reykjavik, Iceland
| | - Einar Stefánsson
- Department of Ophthalmology, Faculty of Medicine, National University Hospital, University of Iceland, Reykjavik, Iceland
| | - Phatsawee Jansook
- Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand
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Solanki N, Pandit D, Desai S. Effectiveness and safety assessment of beta-blockers, calcium channel blockers, and angiotensin receptor blockers in hypertensive patients: a prospective study. AMERICAN JOURNAL OF CARDIOVASCULAR DISEASE 2021; 11:601-610. [PMID: 34849291 PMCID: PMC8611269] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 07/02/2021] [Accepted: 08/23/2021] [Indexed: 06/13/2023]
Abstract
BACKGROUND Hypertension is most common prevailing cardiovascular disease worldwide. In this condition the effectiveness and safety of already available and many time-tested medications should be regularly reviewed. METHODOLOGY Ethical approval of study was obtained from human research ethics committee of the hospital. 180 patients were enrolled with three groups of antihypertensive medication groups as calcium channel blocker (amlodipine), beta blocker (metoprolol) and angiotensin receptor blocker (telmisartan) over a span of eight months. The data was obtained from week zero to twelve (SBP: Systolic Blood Pressure and DBP: Diastolic Blood Pressure). Safety of Beta blocker, calcium channel blocker and angiotensin receptor blocker were investigated. RESULTS Comparison of efficacy between the beta blocker, calcium channel blocker and angiotensin blocker receptor blocker were shown to be non-significant. It indicated that all drug therapies have the same successful reduction of SBP (P-0.4819). No significant adverse reactions were observed in either class of the medicines. CONCLUSION The study showed the efficacy of Calcium Channel Blocker, Beta Blocker and Angiotensin Receptor Blocker in reduction of SBP & DBP was same, while Calcium Channel Blockers were superior to other two medications.
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Affiliation(s)
- Nilay Solanki
- Department of Pharmacology, Ramanbhai Patel College of Pharmacy, Charotar University of Science and Technology, CHARUSAT CampusChanga 388421, Gujarat, India
| | - Dhruvi Pandit
- Department of Pharmacology, Ramanbhai Patel College of Pharmacy, Charotar University of Science and Technology, CHARUSAT CampusChanga 388421, Gujarat, India
| | - Shubha Desai
- Research Department, Dr. Jivraj Mehta Smarak and Health FoundationAhmedabad, Gujarat, India
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Humphrey TJL, James G, Wittbrodt ET, Zarzuela D, Hiemstra TF. Adverse clinical outcomes associated with RAAS inhibitor discontinuation: analysis of over 400 000 patients from the UK Clinical Practice Research Datalink (CPRD). Clin Kidney J 2021; 14:2203-2212. [PMID: 34804520 PMCID: PMC8598122 DOI: 10.1093/ckj/sfab029] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2020] [Accepted: 01/11/2021] [Indexed: 12/25/2022] Open
Abstract
BACKGROUND Users of guideline-recommended renin-angiotensin-aldosterone system (RAAS) inhibitors may experience disruptions to their treatment, e.g. due to hyperkalaemia, hypotension or acute kidney injury. The risks associated with treatment disruption have not been comprehensively assessed; therefore, we evaluated the risk of adverse clinical outcomes in RAAS inhibitor users experiencing treatment disruptions in a large population-wide database. METHODS This exploratory, retrospective analysis utilized data from the UK's Clinical Practice Research Datalink, linked to Hospital Episodes Statistics and the Office for National Statistics databases. Adults (≥18 years) with first RAAS inhibitor use (defined as angiotensin-converting enzyme inhibitors or angiotensin receptor blockers) between 1 January 2009 and 31 December 2014 were eligible for inclusion. Time to the first occurrence of adverse clinical outcomes [all-cause mortality, all-cause hospitalization, cardiac arrhythmia, heart failure hospitalization, cardiac arrest, advancement in chronic kidney disease (CKD) stage and acute kidney injury] was compared between RAAS inhibitor users with and without interruptions or cessations to treatment during follow-up. Associations between baseline characteristics and adverse clinical outcomes were also assessed. RESULTS Among 434 027 RAAS inhibitor users, the risk of the first occurrence of all clinical outcomes, except advancement in CKD stage, was 8-75% lower in patients without interruptions or cessations versus patients with interruptions/cessations. Baseline characteristics independently associated with increased risk of clinical outcomes included increasing age, smoking, CKD, diabetes and heart failure. CONCLUSIONS These findings highlight the need for effective management of factors associated with RAAS inhibitor interruptions or cessations in patients for whom guideline-recommended RAAS inhibitor treatment is indicated.
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Affiliation(s)
| | - Glen James
- Global Medical Affairs, AstraZeneca, Cambridge, UK
| | - Eric T Wittbrodt
- Biopharmaceuticals Medical Unit, AstraZeneca, Gaithersburg, MD, USA
| | - Donna Zarzuela
- Biopharmaceuticals Medical Unit, AstraZeneca, Gaithersburg, MD, USA
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Pulipati VP, Mares JW, Bakris GL. Optimizing Blood Pressure Control Without Adding Anti-Hypertensive Medications. Am J Med 2021; 134:1195-1198. [PMID: 34197786 DOI: 10.1016/j.amjmed.2021.05.021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2021] [Revised: 05/06/2021] [Accepted: 05/07/2021] [Indexed: 11/18/2022]
Affiliation(s)
| | - Jon W Mares
- Department of Medicine, American Heart Association Comprehensive Hypertension Center, Section of Endocrinology, Diabetes and Metabolism, University of Chicago Medicine, Ill
| | - George L Bakris
- Department of Medicine, American Heart Association Comprehensive Hypertension Center, Section of Endocrinology, Diabetes and Metabolism, University of Chicago Medicine, Ill
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Kravchun PG, Kadykova OI, Herasymchuk US. Adipokines in patients with hypertensive disease with obesity in the dynamics of combined antihypertensive therapy. REGULATORY MECHANISMS IN BIOSYSTEMS 2021. [DOI: 10.15421/022149] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
Hypertensive disease today is one of the most common cardiovascular diseases, as well as the most common disease associated with obesity. Evaluation of the level of adipokines, namely adiponutrin and galanin, depending on the degree and duration of hypertension, the degree of obesity and their correction against the background of combined antihypertensive therapy is relevant for further understanding of this comorbidity and improvement of the early diagnostics. 127 people were examined, including 107 patients with hypertension of degree 1–3 and 20 healthy persons. Of the patients included in the study, the adiponutrin and the galanin levels were determined in 58 patients, out of which 22 were prescribed different regimens of combined antihypertensive therapy. To determine the level of adiponutrin and galanin, an enzyme-linked immunosorbent assay was used. A significant increase was found in the blood serum of the examined adipokines in comparison with the control group: the galanin level was 4.8 times higher than in the control group, the adiponutrin level in patients with this comorbid pathology was 3.3 times higher than that in the control group. The galanin level is most pronounced in patients with hypertension of degree 3 and obesity of degree 3, which is confirmed by the presence of a direct correlation with systolic, diastolic and pulse blood pressure, very low density lipoprotein cholesterol. The adiponutrin level in the blood serum increased correspondingly to the increase in body mass index: in patients with obesity of degree 3 it was 15.8 times higher than this indicator in patients with normal body weight, 8.8 times higher than in patients with overweight, 6.1 times higher than in patients with obesity of degree 1 and 2.5 times higher than in patients with obesity of degree 2. The levels of the studied adipokines in patients differed also relative to the duration of hypertension. There was a 1.8-, 5.1-, 5.2-fold increase (respectively, ≤5, 6–10, >10 years) of the galanin content in the blood serum compared to the control group. Also an increase of the serum adiponutrin level was noted in comparison with the control group. Against the background of combined antihypertensive therapy, we observed favourable dynamics of galanin and adiponutrin. It is important to conduct further studies to assess the activity of galanin and adiponutrin with a longer follow-up period in wider populations.
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Rao VU, Reeves DJ, Chugh AR, O'Quinn R, Fradley MG, Raghavendra M, Dent S, Barac A, Lenihan D. Clinical Approach to Cardiovascular Toxicity of Oral Antineoplastic Agents: JACC State-of-the-Art Review. J Am Coll Cardiol 2021; 77:2693-2716. [PMID: 34045027 DOI: 10.1016/j.jacc.2021.04.009] [Citation(s) in RCA: 39] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2021] [Revised: 03/30/2021] [Accepted: 04/06/2021] [Indexed: 12/14/2022]
Abstract
Precision medicine has ushered in a new era of targeted treatments for numerous malignancies, leading to improvements in overall survival. Unlike traditional chemotherapy, many molecular targeted antineoplastic agents are available in oral formulation, leading to enhanced patient convenience and a perception of reduced risk of adverse effects. Although oral antineoplastic agents are generally well-tolerated, cardiovascular toxicities are being reported with increasing frequency in part due to U.S. Food and Drug Administration and manufacturer recommended cardiac monitoring. Monitoring strategies have focused on left ventricular dysfunction, hypertension, and QT prolongation/arrhythmias. Given the rapid pace of development and availability of new oral antineoplastic agents, the purpose of this review is to provide clinicians with an up-to-date practical approach to monitoring and management of cardiovascular toxicities with the aim of improving overall outcomes for patients with cancer.
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Affiliation(s)
- Vijay U Rao
- Franciscan Cardio-Oncology Center, Indiana Heart Physicians, Franciscan Health, Indianapolis, Indiana, USA.
| | - David J Reeves
- Division of Oncology, Franciscan Health and Butler University College of Pharmacy and Health Sciences, Indianapolis, Indiana, USA
| | - Atul R Chugh
- Franciscan Cardio-Oncology Center, Indiana Heart Physicians, Franciscan Health, Indianapolis, Indiana, USA
| | - Rupal O'Quinn
- Cardio-Oncology Center of Excellence, Division of Cardiology, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Michael G Fradley
- Cardio-Oncology Center of Excellence, Division of Cardiology, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Meghana Raghavendra
- Franciscan Cardio-Oncology Center, Oncology and Hematology Specialists, Franciscan Health, Indianapolis, Indiana, USA
| | - Susan Dent
- Duke Cancer Institute, Duke University, Durham, North Carolina, USA
| | - Ana Barac
- Medstar Heart and Vascular Institute, Georgetown University, Washington, DC, USA
| | - Daniel Lenihan
- Cardio-Oncology Center of Excellence, Washington University in St. Louis, St. Louis, Missouri, USA
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