Your browser doesn't support javascript.
loading
: 20 | 50 | 100
1 - 20 de 13.212
1.
Clin Interv Aging ; 19: 681-693, 2024.
Article En | MEDLINE | ID: mdl-38706635

Aging and aging-related diseases present a global public health problem. Therefore, the development of efficient anti-aging drugs has become an important area of research. Traditional Chinese medicine is an important complementary and alternative branch of aging-related diseases therapy. Recently, a growing number of studies have revealed that traditional Chinese medicine has a certain delaying effect on the progression of aging and aging-related diseases. Here, we review the progress in research into using traditional Chinese medicine for aging and aging-related diseases (including neurodegenerative diseases, cardiovascular diseases, diabetes, and cancer). Furthermore, we summarize the potential mechanisms of action of traditional Chinese medicine and provide references for further studies on aging and aging-related diseases.


Aging , Drugs, Chinese Herbal , Medicine, Chinese Traditional , Neoplasms , Neurodegenerative Diseases , Humans , Aging/drug effects , Medicine, Chinese Traditional/methods , Neurodegenerative Diseases/drug therapy , Neoplasms/drug therapy , Drugs, Chinese Herbal/therapeutic use , Drugs, Chinese Herbal/pharmacology , Cardiovascular Diseases/drug therapy , Cardiovascular Diseases/prevention & control , Diabetes Mellitus/drug therapy
2.
J Nanobiotechnology ; 22(1): 263, 2024 May 17.
Article En | MEDLINE | ID: mdl-38760755

The prevalence of cardiovascular diseases continues to be a challenge for global health, necessitating innovative solutions. The potential of high-density lipoprotein (HDL) mimetic nanotherapeutics in the context of cardiovascular disease and the intricate mechanisms underlying the interactions between monocyte-derived cells and HDL mimetic showing their impact on inflammation, cellular lipid metabolism, and the progression of atherosclerotic plaque. Preclinical studies have demonstrated that HDL mimetic nanotherapeutics can regulate monocyte recruitment and macrophage polarization towards an anti-inflammatory phenotype, suggesting their potential to impede the progression of atherosclerosis. The challenges and opportunities associated with the clinical application of HDL mimetic nanotherapeutics, emphasize the need for additional research to gain a better understanding of the precise molecular pathways and long-term effects of these nanotherapeutics on monocytes and macrophages to maximize their therapeutic efficacy. Furthermore, the use of nanotechnology in the treatment of cardiovascular diseases highlights the potential of nanoparticles for targeted treatments. Moreover, the concept of theranostics combines therapy and diagnosis to create a selective platform for the conversion of traditional therapeutic medications into specialized and customized treatments. The multifaceted contributions of HDL to cardiovascular and metabolic health via highlight its potential to improve plaque stability and avert atherosclerosis-related problems. There is a need for further research to maximize the therapeutic efficacy of HDL mimetic nanotherapeutics and to develop targeted treatment approaches to prevent atherosclerosis. This review provides a comprehensive overview of the potential of nanotherapeutics in the treatment of cardiovascular diseases, emphasizing the need for innovative solutions to address the challenges posed by cardiovascular diseases.


Cardiovascular Diseases , Lipoproteins, HDL , Macrophages , Monocytes , Humans , Lipoproteins, HDL/chemistry , Lipoproteins, HDL/metabolism , Lipoproteins, HDL/pharmacology , Macrophages/drug effects , Macrophages/metabolism , Animals , Cardiovascular Diseases/drug therapy , Monocytes/drug effects , Nanoparticles/chemistry , Atherosclerosis/drug therapy , Plaque, Atherosclerotic/drug therapy , Nanomedicine/methods , Biomimetic Materials/chemistry , Biomimetic Materials/pharmacology
4.
BMC Geriatr ; 24(1): 444, 2024 May 21.
Article En | MEDLINE | ID: mdl-38773394

BACKGROUND: Randomized clinical trials have shown that, under optimal conditions, statins reduce the risk of cardiovascular events in older adults. Given the prevalence and consequences of suboptimal adherence to statin among older adults, it is essential to document strategies designed to increase statin adherence in this population. The objective of this systematic review is to describe and summarize the effectiveness of interventions to improve statin adherence in older adults (≥ 65 years old). METHODS: This review followed PRISMA guidelines. Studies were identified from PubMed, PsycINFO, Embase, CINAHL and Web of Science. Study selection was conducted independently by four reviewers working in pairs. Included studies reported data on interventions designed to increase adherence to statin therapy in older adults and were original trials or observational studies. Interventions were pragmatically regrouped into 8 different categories going from patient to administrative level. Two reviewers extracted study data and assessed study quality independently. Given the heterogeneity between the included studies, a narrative critique and summary was conducted. RESULTS: Twelve out of the 2889 identified articles were included in the review. Our review showed that simplifying patients' drug regimen, administrative improvements and large-scale pharmacy-led automated telephone interventions show positive effects on patient adherence to statin therapy, with odds ratios between > 1.0 and 3.0, while education-based strategies and intensified patient care showed mixed results. CONCLUSIONS: Current evidence suggests that some interventions can increase statin adherence in older adults, which could help in the reduction of the risk of a cardiovascular event in this population.


Hydroxymethylglutaryl-CoA Reductase Inhibitors , Medication Adherence , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Aged , Cardiovascular Diseases/prevention & control , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/drug therapy
5.
J Cell Mol Med ; 28(10): e18239, 2024 May.
Article En | MEDLINE | ID: mdl-38774996

The occurrence and development of diabetic vascular diseases are closely linked to inflammation-induced endothelial dysfunction. Puerarin (Pue), the primary component of Pueraria lobata, possesses potent anti-inflammatory properties. However, its vasoprotective role remains elusive. Therefore, we investigated whether Pue can effectively protect against vascular damage induced by diabetes. In the study, Pue ameliorated lipopolysaccharide-adenosine triphosphate (LPS-ATP) or HG-primed cytotoxicity and apoptosis, while inhibited reactive oxygen species (ROS)-mediated NLR family pyrin domain containing 3 (NLRP3) inflammasome in HUVECs, as evidenced by significantly decreased ROS level, NOX4, Caspase-1 activity and expression of NLRP3, GSDMD, cleaved caspase-1, IL-1ß and IL-18. Meanwhile, ROS inducer CoCI2 efficiently weakened the effects of Pue against LPS-ATP-primed pyroptosis. In addition, NLRP3 knockdown notably enhanced Pue's ability to suppress pyroptosis in LPS-ATP-primed HUVECs, whereas overexpression of NLRP3 reversed the inhibitory effects of Pue. Furthermore, Pue inhibited the expression of ROS and NLRP3 inflammasome-associated proteins on the aorta in type 2 diabetes mellitus rats. Our findings indicated that Pue might ameliorate LPS-ATP or HG-primed damage in HUVECs by inactivating the ROS-NLRP3 signalling pathway.


Adenosine Triphosphate , Human Umbilical Vein Endothelial Cells , Inflammasomes , Isoflavones , Lipopolysaccharides , NLR Family, Pyrin Domain-Containing 3 Protein , Reactive Oxygen Species , Signal Transduction , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Reactive Oxygen Species/metabolism , Isoflavones/pharmacology , Isoflavones/therapeutic use , Humans , Animals , Signal Transduction/drug effects , Human Umbilical Vein Endothelial Cells/metabolism , Rats , Male , Adenosine Triphosphate/metabolism , Inflammasomes/metabolism , Cardiovascular Diseases/metabolism , Cardiovascular Diseases/etiology , Cardiovascular Diseases/drug therapy , Diabetes Mellitus, Experimental/metabolism , Diabetes Mellitus, Experimental/complications , Pyroptosis/drug effects , Rats, Sprague-Dawley , Endothelial Cells/metabolism , Endothelial Cells/drug effects , Glucose/metabolism , Apoptosis/drug effects
6.
Curr Probl Cardiol ; 49(7): 102637, 2024 Jul.
Article En | MEDLINE | ID: mdl-38735347

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide. Hyperlipidemia, particularly elevated low-density lipoprotein cholesterol (LDL-C) is one of the major risk factors for CVD. Major landmark cardiovascular outcome clinical trials demonstrated that LDL-C lowering medications reduce cardiovascular events, and the lower the LDL-C the better the outcome. This article discusses the evolution of LDL-C lowering medications starting from bile acid sequestrants (BAS), statin therapy, bempedoic acid, the proprotein convertase subtilisin kexin 9 (PCSK9) synthesis inhibitor, novel small interfering RNA-based therapy (inclisiran) to the most recent oral PCSK9 inhibitors (MK-0616) which is currently under phase 3 clinical trial studies.


Cardiovascular Diseases , Cholesterol, LDL , Humans , Cardiovascular Diseases/prevention & control , Cardiovascular Diseases/drug therapy , Cholesterol, LDL/blood , Anticholesteremic Agents/therapeutic use , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , PCSK9 Inhibitors , Dicarboxylic Acids , Fatty Acids , RNA, Small Interfering
7.
Molecules ; 29(9)2024 May 02.
Article En | MEDLINE | ID: mdl-38731591

Angelica sinensis (Oliv.) Diels (A. sinensis) is a medicinal and edible values substance, which could promote blood circulation and enrich blood. It possesses rich chemical components and nutrients, which have significant therapeutic effects on cardiovascular and cerebrovascular diseases. It is commonly used for the prevention and treatment of cardiovascular and cerebrovascular diseases in the elderly, especially in improving ischemic damage to the heart and brain, protecting vascular cells, and regulating inflammatory reactions. This article reviews the main pharmacological effects and clinical research of A. sinensis on cardiovascular and cerebrovascular diseases in recent years, explores the effect of its chemical components on cardiovascular and cerebrovascular diseases by regulating the expression of functional proteins and inhibiting inflammation, anti-apoptosis, and antioxidant mechanisms. It provides a reference for further research on A. sinensis and the development of related drugs. It provides a new reference direction for the in-depth research and application of A. sinensis in the prevention, improvement, and treatment of cardiovascular and cerebrovascular diseases.


Angelica sinensis , Cardiovascular Diseases , Cerebrovascular Disorders , Humans , Angelica sinensis/chemistry , Cerebrovascular Disorders/drug therapy , Cerebrovascular Disorders/metabolism , Cardiovascular Diseases/drug therapy , Animals , Antioxidants/pharmacology , Antioxidants/chemistry , Plant Extracts/pharmacology , Plant Extracts/chemistry
8.
Respir Res ; 25(1): 207, 2024 May 15.
Article En | MEDLINE | ID: mdl-38750572

BACKGROUND: The evidence regarding effects of statins on exacerbation risk in COPD remains controversial. Previous studies often excluded patients with cardiovascular comorbidities despite their high prevalence in COPD and role for exacerbations. Based on the cardioprotective properties of statins, we hypothesised that statins may reduce the risk of exacerbations especially in patients with cardiovascular comorbidities. METHODS: One thousand eight hundred eighty seven patients of the German COPD cohort COSYCONET (COPD and Systemic Consequences Comorbidities Network) of GOLD grades 1-4 (37.8% female, mean age 64.78 ± 8.3) were examined at baseline and over a period of 4.5 years for the occurrence of at least one exacerbation or severe exacerbation per year in cross-sectional and longitudinal analyses adjusted for age, gender, BMI, GOLD grade and pack-years. Due to their collinearity, various cardiovascular diseases were tested in separate analyses, whereby the potential effect of statins in the presence of a specific comorbidity was tested as interaction between statins and comorbidity. We also identified patients who never took statins, always took statins, or initiated statin intake during the follow-up. RESULTS: One thousand three hundred six patients never took statins, 31.6% were statin user, and 12.9% initiated statins during the follow-up. Most cardiovascular diseases were significantly (p < 0.05)may associated with an increased risk of COPD exacerbations, but in none of them the intake of statins was a significant attenuating factor, neither overall nor in modulating the increased risk linked to the specific comorbidities. The results of the cross-sectional and longitudinal analyses were consistent with each other, also those regarding at least 1 exacerbation or at least 1 severe exacerbation per year. CONCLUSION: These findings complement the existing literature and may suggest that even in patients with COPD, cardiovascular comorbidities and a statin therapy that targets these comorbidities, the effects of statins on exacerbation risk are either negligible or more subtle than a reduction in exacerbation frequency. TRIAL REGISTRATION: Trial registration ClinicalTrials.gov, Identifier: NCT01245933. Other Study ID (BMBF grant): 01GI0881, registered 18 November 2010, study start 2010-11, primary completion 2013-12, study completion 2023-09. https://clinicaltrials.gov/study/NCT01245933?cond=COPD&term=COSYCONET&rank=3.


Cardiovascular Diseases , Comorbidity , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Pulmonary Disease, Chronic Obstructive , Humans , Pulmonary Disease, Chronic Obstructive/epidemiology , Pulmonary Disease, Chronic Obstructive/drug therapy , Pulmonary Disease, Chronic Obstructive/diagnosis , Female , Male , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Middle Aged , Aged , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/drug therapy , Cardiovascular Diseases/prevention & control , Cross-Sectional Studies , Cohort Studies , Longitudinal Studies , Disease Progression , Germany/epidemiology , Follow-Up Studies
9.
Nat Commun ; 15(1): 3962, 2024 May 10.
Article En | MEDLINE | ID: mdl-38730247

Lanifibranor, a pan-PPAR agonist, improves liver histology in patients with metabolic dysfunction-associated steatohepatitis (MASH), who have poor cardiometabolic health (CMH) and cardiovascular events as major mortality cause. NATIVE trial secondary and exploratory outcomes (ClinicalTrials.gov NCT03008070) were analyzed for the effect of lanifibranor on IR, lipid and glucose metabolism, systemic inflammation, blood pressure (BP), hepatic steatosis (imaging and histological grading) for all patients of the original analysis. With lanifibranor, triglycerides, HDL-C, apolipoproteins, insulin, HOMA-IR, HbA1c, fasting glucose (FG), hs-CRP, ferritin, diastolic BP and steatosis improved significantly, independent of diabetes status: most patients with prediabetes returned to normal FG levels. Significant adiponectin increases correlated with hepatic and CMH marker improvement; patients had an average weight gain of 2.5 kg, with 49% gaining ≥2.5% weight. Therapeutic benefits were similar regardless of weight change. Here, we show that effects of lanifibranor on liver histology in MASH are accompanied with CMH improvement, indicative of potential cardiovascular clinical benefits.


Chalcones , Adult , Aged , Female , Humans , Male , Middle Aged , Adiponectin/metabolism , Adiponectin/blood , Blood Glucose/metabolism , Blood Glucose/drug effects , Blood Pressure/drug effects , Cardiovascular Diseases/drug therapy , Chalcones/therapeutic use , Chalcones/pharmacology , Fatty Liver/drug therapy , Fatty Liver/metabolism , Insulin Resistance , Lipid Metabolism/drug effects , Liver/drug effects , Liver/pathology , Liver/metabolism , Peroxisome Proliferator-Activated Receptors/agonists , Peroxisome Proliferator-Activated Receptors/metabolism , Propionates , Triglycerides/blood , Triglycerides/metabolism
10.
BMC Med ; 22(1): 201, 2024 May 20.
Article En | MEDLINE | ID: mdl-38764043

BACKGROUND: Lipid-lowering drugs and antihypertensive drugs are commonly combined for cardiovascular disease (CVD). However, the relationship of combined medications with CVD remains controversial. We aimed to explore the associations of genetically proxied medications of lipid-lowering and antihypertensive drugs, either alone or both, with risk of CVD, other clinical and safety outcomes. METHODS: We divided 423,821 individuals in the UK Biobank into 4 groups via median genetic scores for targets of lipid-lowering drugs and antihypertensive drugs: lower low-density lipoprotein cholesterol (LDL-C) mediated by targets of statins or proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, lower systolic blood pressure (SBP) mediated by targets of ß-blockers (BBs) or calcium channel blockers (CCBs), combined genetically lower LDL-C and SBP, and reference (genetically both higher LDL-C and SBP). Associations with risk of CVD and other clinical outcomes were explored among each group in factorial Mendelian randomization. RESULTS: Independent and additive effects were observed between genetically proxied medications of lipid-lowering and antihypertensive drugs with CVD (including coronary artery disease, stroke, and peripheral artery diseases) and other clinical outcomes (ischemic stroke, hemorrhagic stroke, heart failure, diabetes mellitus, chronic kidney disease, and dementia) (P > 0.05 for interaction in all outcomes). Take the effect of PCSK9 inhibitors and BBs on CVD for instance: compared with the reference, PCSK9 group had a 4% lower risk of CVD (odds ratio [OR], 0.96; 95%CI, 0.94-0.99), and a 3% lower risk was observed in BBs group (OR, 0.97; 95%CI, 0.94-0.99), while combined both were associated with a 6% additively lower risk (OR, 0.94; 95%CI, 0.92-0.97; P = 0.87 for interaction). CONCLUSIONS: Genetically proxied medications of combined lipid-lowering and antihypertensive drugs have an independent and additive effects on CVD, other clinical and safety outcomes, with implications for CVD clinical practice, subsequent trials as well as drug development of polypills.


Antihypertensive Agents , Cardiovascular Diseases , Mendelian Randomization Analysis , Humans , Antihypertensive Agents/therapeutic use , Cardiovascular Diseases/genetics , Cardiovascular Diseases/drug therapy , Male , Female , Hypolipidemic Agents/therapeutic use , Middle Aged , Aged , Genetic Variation , United Kingdom/epidemiology , Drug Therapy, Combination , Blood Pressure/drug effects
11.
Mar Drugs ; 22(5)2024 May 03.
Article En | MEDLINE | ID: mdl-38786601

Ageing represents a main risk factor for several pathologies. Among them, cardiovascular diseases (CVD) and type 2 diabetes mellitus (T2DM) are predominant in the elderly population and often require prolonged use of multiple drugs due to their chronic nature and the high proportion of co-morbidities. Hence, research is constantly looking for novel, effective molecules to treat CVD and T2DM with minimal side effects. Marine active compounds, holding a great diversity of chemical structures and biological properties, represent interesting therapeutic candidates to treat these age-related diseases. This review summarizes the current state of research on marine compounds for the treatment of CVD and T2DM, from pre-clinical studies to clinical investigations and approved drugs, highlighting the potential of marine compounds in the development of new therapies, together with the limitations in translating pre-clinical results into human application.


Aquatic Organisms , Cardiovascular Diseases , Diabetes Mellitus, Type 2 , Humans , Cardiovascular Diseases/drug therapy , Diabetes Mellitus, Type 2/drug therapy , Animals , Hypoglycemic Agents/therapeutic use , Hypoglycemic Agents/pharmacology , Aging/drug effects , Biological Products/therapeutic use , Biological Products/pharmacology , Drug Evaluation, Preclinical
12.
Mar Drugs ; 22(5)2024 May 17.
Article En | MEDLINE | ID: mdl-38786620

Heart disease is one of the leading causes of death worldwide, and it is estimated that 17.9 million people die of it each year. The risk factors for cardiovascular diseases are attributable to an unhealthy and sedentary lifestyle, poor nutrition, stress, genetic predisposition, diabetes, obesity, and aging. Marine microalgae have been the subject of numerous studies for their potential activity against several human diseases. They produce a plethora of primary and secondary metabolites such as essential nutrients, vitamins, pigments, and omega-3 fatty acid. Many of these molecules have antioxidant properties and have been shown to play a role in the prevention of heart diseases. The aim of this review is to summarize recent studies on the discovery of marine microalgal compounds and bioactivities for cardiovascular diseases, including in vitro and in vivo studies, showing and discussing recent discoveries and trends. The most promising results were found for microalgal polysaccharides, peptides and carotenoids. In conclusion, the overall data summarized here show that microalgae-based supplementation has the potential to improve age-related cardiovascular diseases and we expect more clinical studies in the future.


Cardiovascular Diseases , Microalgae , Humans , Cardiovascular Diseases/drug therapy , Animals , Aging/drug effects , Antioxidants/pharmacology , Biological Products/pharmacology , Aquatic Organisms , Dietary Supplements
13.
BMJ Open ; 14(5): e082228, 2024 May 22.
Article En | MEDLINE | ID: mdl-38777587

OBJECTIVE: Hospitalisation due to medication-related problems is a major health concern, particularly for those with pre-existing, or those at high risk of developing cardiovascular disease (CVD). Postdischarge medication reviews (PDMRs) may form a core component of reducing hospital readmissions due to medication-related problems. This study aimed to explore postdischarge CVD patients' perspectives of, and experiences with, pharmacist-led medication management services. A secondary aim explored attitudes towards the availability of PDMRs. DESIGN: An interpretative qualitative study involving 16 semistructured interviews. Data were analysed using an inductive thematic approach. SETTING: Patients with CVD discharged to a community setting from the John Hunter Hospital, an 820-bed tertiary referral hospital based in New South Wales, Australia. PARTICIPANTS: Patients with pre-existing or newly diagnosed CVD who were recently discharged from the hospital. RESULTS: A total of 16 interviews were conducted to reach thematic saturation. Nine participants (56%) were male. The mean age of participants was 57.5 (±13.2) years. Three emergent themes were identified: (1) poor medication understanding impacts transition from the hospital to home; (2) factors influencing medication concordance following discharge and (3) perceived benefits of routine PDMRs. CONCLUSIONS: There is a clear need to further improve the quality use of medicines and health literacy of transition-of-care patients with CVD. Our findings indicate that the engagement of transition-of-care patients with CVD with pharmacist-led medication management services is minimal. Pharmacists are suitable to provide essential and tailored medication review services to patients with CVD as part of a multidisciplinary healthcare team. The implementation of routine, pharmacist-led PDMRs may be a feasible means of providing patients with access to health education following their transition from hospital back to community, improving their health literacy and reducing rehospitalisations due to medication-related issues.


Cardiovascular Diseases , Patient Discharge , Pharmacists , Qualitative Research , Humans , Male , Female , Middle Aged , Cardiovascular Diseases/drug therapy , Aged , New South Wales , Medication Therapy Management/organization & administration , Adult , Interviews as Topic , Professional Role , Medication Adherence
14.
Int J Mol Sci ; 25(10)2024 May 12.
Article En | MEDLINE | ID: mdl-38791306

Computational drug-repositioning technology is an effective tool for speeding up drug development. As biological data resources continue to grow, it becomes more important to find effective methods to identify potential therapeutic drugs for diseases. The effective use of valuable data has become a more rational and efficient approach to drug repositioning. The disease-drug correlation method (DDCM) proposed in this study is a novel approach that integrates data from multiple sources and different levels to predict potential treatments for diseases, utilizing support-vector regression (SVR). The DDCM approach resulted in potential therapeutic drugs for neoplasms and cardiovascular diseases by constructing a correlation hybrid matrix containing the respective similarities of drugs and diseases, implementing the SVR algorithm to predict the correlation scores, and undergoing a randomized perturbation and stepwise screening pipeline. Some potential therapeutic drugs were predicted by this approach. The potential therapeutic ability of these drugs has been well-validated in terms of the literature, function, drug target, and survival-essential genes. The method's feasibility was confirmed by comparing the predicted results with the classical method and conducting a co-drug analysis of the sub-branch. Our method challenges the conventional approach to studying disease-drug correlations and presents a fresh perspective for understanding the pathogenesis of diseases.


Algorithms , Drug Repositioning , Drug Repositioning/methods , Humans , Support Vector Machine , Computational Biology/methods , Neoplasms/drug therapy , Cardiovascular Diseases/drug therapy
15.
J Ethnopharmacol ; 331: 118287, 2024 Sep 15.
Article En | MEDLINE | ID: mdl-38705429

ETHNOPHARMACOLOGICAL RELEVANCE: Cardiovascular and cerebrovascular diseases are the leading causes of death worldwide and interact closely with each other. Danhong Injection (DHI) is a widely used preparation for the co-treatment of brain and heart diseases (CTBH). However, the underlying molecular endotype mechanisms of DHI in the CTBH remain unclear. AIM OF THIS STUDY: To elucidate the underlying endotype mechanisms of DHI in the CTBH. MATERIALS AND METHODS: In this study, we proposed a modular-based disease and drug-integrated analysis (MDDIA) strategy for elucidating the systematic CTBH mechanisms of DHI using high-throughput transcriptome-wide sequencing datasets of DHI in the treatment of patients with stable angina pectoris (SAP) and cerebral infarction (CI). First, we identified drug-targeted modules of DHI and disease modules of SAP and CI based on the gene co-expression networks of DHI therapy and the protein-protein interaction networks of diseases. Moreover, module proximity-based topological analyses were applied to screen CTBH co-module pairs and driver genes of DHI. At the same time, the representative driver genes were validated via in vitro experiments on hypoxia/reoxygenation-related cardiomyocytes and neuronal cell lines of H9C2 and HT22. RESULTS: Seven drug-targeted modules of DHI and three disease modules of SAP and CI were identified by co-expression networks. Five modes of modular relationships between the drug and disease modules were distinguished by module proximity-based topological analyses. Moreover, 13 targeted module pairs and 17 driver genes associated with DHI in the CTBH were also screened. Finally, the representative driver genes AKT1, EDN1, and RHO were validated by in vitro experiments. CONCLUSIONS: This study, based on clinical sequencing data and modular topological analyses, integrated diseases and drug targets. The CTBH mechanism of DHI may involve the altered expression of certain driver genes (SRC, STAT3, EDN1, CYP1A1, RHO, RELA) through various enriched pathways, including the Wnt signaling pathway.


Drugs, Chinese Herbal , Protein Interaction Maps , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/administration & dosage , Humans , Animals , Cerebrovascular Disorders/drug therapy , Cerebrovascular Disorders/genetics , Gene Regulatory Networks/drug effects , Cardiovascular Diseases/drug therapy , Cardiovascular Diseases/genetics , Transcriptome/drug effects , Myocytes, Cardiac/drug effects , Myocytes, Cardiac/metabolism , Injections
16.
J Med Chem ; 67(10): 7825-7835, 2024 May 23.
Article En | MEDLINE | ID: mdl-38729623

Cardiac myosin activation has been shown to be a viable approach for the treatment of heart failure with reduced ejection fraction. Here, we report the discovery of nelutroctiv (CK-136), a selective cardiac troponin activator intended for patients with cardiovascular conditions where cardiac contractility is reduced. Discovery of nelutroctiv began with a high-throughput screen that identified compound 1R, a muscle selective cardiac sarcomere activator devoid of phosphodiesterase-3 activity. Optimization of druglike properties for 1R led to the replacement of the sulfonamide and aniline substituents which resulted in improved pharmacokinetic (PK) profiles and a reduced potential for human drug-drug interactions. In vivo echocardiography assessment of the optimized leads showed concentration dependent increases in fractional shortening and an improved pharmacodynamic window compared to myosin activator CK-138. Overall, nelutroctiv was found to possess the desired selectivity, a favorable pharmacodynamic window relative to myosin activators, and a preclinical PK profile to support clinical development.


Myocardial Contraction , Humans , Animals , Myocardial Contraction/drug effects , Cardiovascular Diseases/drug therapy , Rats , Structure-Activity Relationship , Male , Drug Discovery , Troponin/metabolism , Mice , Rats, Sprague-Dawley , Sulfonamides/pharmacology , Sulfonamides/pharmacokinetics , Sulfonamides/chemistry , Sulfonamides/therapeutic use , Sulfonamides/chemical synthesis
17.
Am J Ther ; 31(3): e237-e245, 2024.
Article En | MEDLINE | ID: mdl-38691663

BACKGROUND: Sex differences (SDs) in pharmacology of cardiovascular (CV) drugs have been described previously; however, paradoxically, there are scarce recommendations in therapy based on these differences. It is of utmost importance to identify whether these SDs determine a modified clinical response and the potential practical implications for this, to provide a base for personalized medicine. AREA OF UNCERTAINTY: The aim of this article was to outline the most important pharmacological drivers of cardiovascular drugs that differ between women and men, along with their implications and challenges in clinical practice. DATA SOURCES: A detailed assessment of English-written resources reflecting SDs impact in CV drug pharmacology was performed using PubMed and Embase databases. RESULTS: Despite large variations in CV drug pharmacokinetics and pharmacodynamics in individuals, correcting for height, weight, surface area, and body composition compensate for most "sex-dependent" differences. In addition, individual, cultural, and social factors significantly impact disease management in women versus men. Gender-biased prescribing patterns and gender-dependent adherence to therapy also influence outcomes. The development of sex-specific guidelines requires that they should reflect the SDs implications for the management of a disease and that the evidence should be carefully evaluated as to whether there is an adequate representation of both sexes and whether sex-disaggregated data are reported. CONCLUSIONS: Pharmacological drivers are under the influence of an impressive number of differences between women and men. However, to establish their significance in clinical practice, an adequate representation of women in studies and the reporting of distinct results is mandatory.


Cardiovascular Agents , Cardiovascular Diseases , Humans , Female , Male , Cardiovascular Diseases/drug therapy , Sex Factors , Cardiovascular Agents/therapeutic use , Cardiovascular Agents/pharmacology , Sex Characteristics , Practice Patterns, Physicians'/statistics & numerical data , Practice Patterns, Physicians'/standards
18.
Sr Care Pharm ; 39(6): 212-217, 2024 Jun 01.
Article En | MEDLINE | ID: mdl-38803027

Background In 2019, the American College of Cardiology and American Heart Association updated their joint guidelines stating low-dose aspirin should not be used on a routine basis for primary prevention of atherosclerotic cardiovascular disease (ASCVD) among people older than 70 years of age because of increased bleeding risk.1 In addition to these updated guidelines, a statement released by the US Preventive Services Task Force in April 2022 recommends against the initiation of low-dose aspirin for primary prevention of cardiovascular disease in people 60 years of age or older.² Despite these updated recommendations, aspirin continues to be a common medication older patients take, providing an opportunity for a clinical pharmacist deprescribing intervention. Objective To identify the role of a pharmacist-led aspirin deprescribing intervention within a safety-net health system in the outpatient setting. Methods This project included patients 70 years of age and older who had aspirin listed as an active medication without documented ASCVD. This project assessed aspirin deprescribing rates, time spent on pharmacist outreach, and reasons for patient and/or provider refusal to discontinue aspirin. Results One hundred thirty-one eligible patients were contacted. Of those, 78 (60%) patients discontinued aspirin after speaking with the pharmacist, and 8 patients discontinued aspirin after a clinical pharmacist recommendation to the patient's primary care provider (PCP). The median time spent on outreach was approximately eight minutes. Of the 6 patients who consented to the project but declined to discontinue aspirin therapy based on pharmacist intervention, 5 preferred to discuss the issue with their PCP, while 1 patient was told by an outside provider to take aspirin. Conclusion Results indicate the successful impact a clinical pharmacist may have in deprescribing aspirin in a high-risk population. These data may also suggest that an active and intentional approach to deprescribing is likely to be more effective than a written recommendation to providers.


Aspirin , Deprescriptions , Pharmacists , Humans , Aspirin/therapeutic use , Aspirin/administration & dosage , Aged , Male , Female , Aged, 80 and over , Outpatients , Professional Role , Cardiovascular Diseases/prevention & control , Cardiovascular Diseases/drug therapy , Primary Prevention/methods , Platelet Aggregation Inhibitors/therapeutic use , Platelet Aggregation Inhibitors/administration & dosage , Ambulatory Care
19.
Sr Care Pharm ; 39(6): 218-227, 2024 Jun 01.
Article En | MEDLINE | ID: mdl-38803024

Background National guidelines no longer recommend adults 60 years of age and older to begin treatment with low-dose daily aspirin for primary prevention of atherosclerotic cardiovascular disease (CVD) due to a lack of proven net benefit and a higher risk of bleeding. Objective The objective of this cross-sectional retrospective analysis was to evaluate the appropriateness of low-dose aspirin prescribing and subsequent gastrointestinal bleeding in older persons receiving primary care in a large academic health system. Setting Large, academic health system within Colorado. Patients Patients with an active order for daily low-dose aspirin as of July 1, 2021, were assessed for appropriateness based on indication (primary vs secondary prevention) and use of a concomitant proton-pump inhibitor (PPI). Incident gastrointestinal bleeds (GIBs) in the subsequent 12 months and GIB risk factors were also evaluated. Results A total of 19,525 patients were included in the analysis. Eighty-nine percent of patients identified as White and 54% identified as male. Of the total cohort, 44% had CVD and 19% were co-prescribed a PPI. GIB occurred in 247 patients (1.27%) within the subsequent year. Risk factors significantly associated with a GIB within 1 year included: history of GIB, history of peptic ulcer disease, other esophageal issue (esophagitis, Barrett's esophagus, Mallory Weiss tears, etc.), 75 years of age or older, and history of gastroesophageal reflux disease. Conclusion This evaluation found that many older persons at this institution may be inappropriately prescribed aspirin, providing opportunities for pharmacists to improve medication safety by deprescribing aspirin among primary prevention patients or potentially co-prescribing a PPI in secondary prevention patients.


Aspirin , Gastrointestinal Hemorrhage , Humans , Aspirin/adverse effects , Aspirin/therapeutic use , Aspirin/administration & dosage , Male , Gastrointestinal Hemorrhage/prevention & control , Gastrointestinal Hemorrhage/chemically induced , Gastrointestinal Hemorrhage/epidemiology , Female , Aged , Retrospective Studies , Middle Aged , Cross-Sectional Studies , Proton Pump Inhibitors/therapeutic use , Proton Pump Inhibitors/administration & dosage , Proton Pump Inhibitors/adverse effects , Aged, 80 and over , Colorado/epidemiology , Primary Health Care , Risk Factors , Platelet Aggregation Inhibitors/adverse effects , Platelet Aggregation Inhibitors/therapeutic use , Platelet Aggregation Inhibitors/administration & dosage , Primary Prevention , Academic Medical Centers , Secondary Prevention/methods , Cardiovascular Diseases/prevention & control , Cardiovascular Diseases/drug therapy
20.
BMJ Open ; 14(5): e078431, 2024 May 09.
Article En | MEDLINE | ID: mdl-38724060

OBJECTIVES: To investigate the time course of medication adherence and some of the factors involved in this process in undocumented migrants with chronic diseases. DESIGN: Retrospective cohort study. SETTING: A big non-governmental organisation in Milano, Italy, giving medical assistance to undocumented migrants. PARTICIPANTS: 1918 patients, 998 females and 920 males, with at least one chronic condition (diabetes, cardiovascular diseases (CVDs), mental health disorders) seen over a period of 10 years (2011-2020). Their mean age was 49.2±13 years. RESULTS: Adherence to medications decreased over 1 year in all patients. This was more evident during the first 2 months of treatment. Patients on only one medication were less adherent than those on more than one medication; at 6 months the percentage of patients with high adherence was 33% vs 57% (p<0.0001) for diabetes, 15% vs 46% (p<0.0001) for mental disorders and 35% vs 59% (p<0.0001) for CVDs. Patients with mental disorders had the lowest adherence: 25% at 6 months and 3% at 1 year. Mental disorders, when present as comorbidities, greatly reduced the probability of being highly adherent: risk ratio (RR) 0.72 (95% CI 0.57 to 0.91; p=0.006) at 3 months, RR 0.77, (95% CI 0.59 to 1.01; p=0.06) at 6 months, RR 0.35 (95% CI 0.13 to 0.94; p=0.04) at 1 year. This was especially evident for patients with CVDs, whose percentage of high adherents decreased to 30% (p=0.0008) at 6 months and to 3% (p=0.01) at 1 year. We also noted that highly adherent patients usually were those most frequently seen by a doctor. CONCLUSIONS: Interventions to increase medication adherence of undocumented migrants with chronic diseases are necessary, particularly in the first 2 months after beginning treatment. These should be aimed at people-centred care and include more outpatient consultations. Educational interventions should especially be taken into consideration for patients on monotherapy.


Medication Adherence , Mental Disorders , Transients and Migrants , Humans , Male , Female , Retrospective Studies , Medication Adherence/statistics & numerical data , Middle Aged , Chronic Disease/drug therapy , Italy , Adult , Transients and Migrants/statistics & numerical data , Transients and Migrants/psychology , Mental Disorders/drug therapy , Cardiovascular Diseases/drug therapy , Diabetes Mellitus/drug therapy
...