Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 11.278
Filtrar
1.
Int J Mol Sci ; 22(11)2021 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-34198942

RESUMO

Empagliflozin (EMPA) is a sodium-glucose transporter 2 (SGLT2) inhibitor that functions as a new-generation glucose-lowering agent and has been proven to be beneficial for patients with cardiovascular diseases. However, the possible benefits and mechanisms of its antiarrhythmic effects in cardiac tissue have not yet been reported. In this study, we elucidated the possible antiarrhythmic effects and mechanisms of EMPA treatment in cardiac tissues of metabolic syndrome (MS) mice. A total of 20 C57BL/6J mice (age: 8 weeks) were divided into four groups: (1) control group, mice fed a standard chow for 16 weeks; (2) MS group, mice fed a high-fat diet for 16 weeks; (3) EMPA group, mice fed a high-fat diet for 12 weeks and administered EMPA at 10 mg/kg daily for the following 4 weeks; and (4) glibenclamide (GLI) group, mice fed a high-fat diet for 12 weeks and administered GLI at 0.6 mg/kg daily for the following 4 weeks. All mice were sacrificed after 16 weeks of feeding. The parameters of electrocardiography (ECG), echocardiography, and the effective refractory period (ERP) of the left ventricle were recorded. The histological characteristics of cardiac tissue, including connexin (Cx) expression and fibrotic areas, were also evaluated. Compared with the MS group, the ECG QT interval in the EMPA group was significantly shorter (57.06 ± 3.43 ms vs. 50.00 ± 2.62 ms, p = 0.011). The ERP of the left ventricle was also significantly shorter in the EMPA group than that in the GLI group (20.00 ± 10.00 ms vs. 60.00 ± 10.00 ms, p = 0.001). The expression of Cx40 and Cx43 in ventricular tissue was significantly lower in the MS group than in the control group. However, the downregulation of Cx40 and Cx43 was significantly attenuated in the EMPA group compared with the MS and GLI groups. The fibrotic areas of ventricular tissue were also fewer in the EMPA group than that in the MS group. In this study, the ECG QT interval in the EMPA group was shorter than that in the MS group. Compared with the MS group, the EMPA group exhibited significant attenuation of downregulated connexin expression and significantly fewer fibrotic areas in ventricles. These results may provide evidence of possible antiarrhythmic effects of EMPA.


Assuntos
Compostos Benzidrílicos/farmacologia , Doenças Cardiovasculares/tratamento farmacológico , Conexina 43/genética , Conexinas/genética , Glucosídeos/farmacologia , Transportador 2 de Glucose-Sódio/genética , Animais , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/patologia , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Ecocardiografia , Eletrocardiografia , Regulação da Expressão Gênica/efeitos dos fármacos , Glucose/metabolismo , Glibureto/farmacologia , Humanos , Síndrome Metabólica/tratamento farmacológico , Síndrome Metabólica/genética , Camundongos , Transportador 2 de Glucose-Sódio/efeitos dos fármacos
2.
Curr Protoc ; 1(7): e189, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34232575

RESUMO

Cardiovascular pharmacogenomics is the study and identification of genomic markers that are associated with variability in cardiovascular drug response, cardiovascular drug-related outcomes, or cardiovascular drug-related adverse events. This overview presents an introduction and historical background to cardiovascular pharmacogenomics, and a protocol for designing a cardiovascular pharmacogenomics study. Important considerations are also included for constructing a cardiovascular pharmacogenomics phenotype, designing the replication or validation strategy, common statistical approaches, and how to put the results in context with the cardiovascular drug or cardiovascular disease under investigation. © 2021 Wiley Periodicals LLC. Basic Protocol: Designing a cardiovascular pharmacogenomics study.


Assuntos
Fármacos Cardiovasculares , Doenças Cardiovasculares , Fármacos Cardiovasculares/efeitos adversos , Doenças Cardiovasculares/tratamento farmacológico , Humanos , Farmacogenética , Testes Farmacogenômicos , Fenótipo
3.
S D Med ; 74(3): 132-135, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34232594

RESUMO

Diabetes mellitus remains one of the most common and disabling diseases in the world. Patients with diabetes tend to have more cardiovascular complications, regardless of their prior cardiac history. Tight glycemic control has been shown to prevent microvascular complications as it relates to nephropathy and retinopathy; however, it hasn't been proven beneficial in patients with macrovascular diseases, i.e., cardiovascular disease. In fact, two groups of diabetic medications, dual peroxisome-proliferator-activated receptor - agonists and sulfonylurea, are known to worsen cardiovascular disease. Patients using this group of medications have shown increased heart failure readmission rates and increased risk for cardiovascular death. Insulin and Metformin have been the gold standard treatment for diabetes management to prevent worsening cardiac outcomes, and now a newer class of medications have demonstrated similar results. These drug classes includes sodium glucose cotransporter 2(SGLT 2) inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, and glucagon like peptide-1 (GLP 1) analogues.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Inibidores da Dipeptidil Peptidase IV , Inibidores do Transportador 2 de Sódio-Glicose , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Peptídeo 1 Semelhante ao Glucagon , Humanos , Hipoglicemiantes/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico
4.
Int J Mol Sci ; 22(12)2021 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-34207143

RESUMO

Epidemiological studies have emphasized the association between a diet rich in fruits and vegetables and a lower frequency of occurrence of inflammatory-related disorders. Black chokeberry (Aronia melanocarpa L.) is a valuable source of biologically active compounds that have been widely investigated for their role in health promotion and cardiovascular disease prevention. Many in vitro and in vivo studies have demonstrated that consumption of these fruits is associated with significant improvements in hypertension, LDL oxidation, lipid peroxidation, total plasma antioxidant capacity and dyslipidemia. The mechanisms for these beneficial effects include upregulation of endothelial nitric oxide synthase, decreased oxidative stress, and inhibition of inflammatory gene expression. Collected findings support the recommendation of such berries as an essential fruit group in a heart-healthy diet. The aim of this review was to summarize the reports on the impact of black chokeberry fruits and extracts against several cardiovascular diseases, e.g., hyperlipidemia, hypercholesterolemia, hypertension, as well as to provide an analysis of the antioxidant and anti-inflammatory effect of these fruits in the abovementioned disorders.


Assuntos
Frutas/química , Photinia/química , Extratos Vegetais/farmacologia , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/prevenção & controle , Humanos , Doenças Metabólicas/diagnóstico , Doenças Metabólicas/tratamento farmacológico , Doenças Metabólicas/etiologia , Estrutura Molecular , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/química , Polifenóis/química , Polifenóis/farmacologia
5.
Ann Med ; 53(1): 874-884, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34096808

RESUMO

BACKGROUND: Statins are widely used to treat people with metabolic and cardiovascular disorders. The effect of statins on coronavirus disease 2019 (COVID-19) is unclear. To investigate the association between statins and COVID-19 outcomes and, if possible, identify the subgroup population that benefits most from statin use. MATERIALS AND METHODS: A systematic review and meta-analysis of published studies that included statin users and described COVID-19 outcomes through 10 November 2020. This study used the generic inverse variance method to perform meta-analyses with random-effects modelling. The main outcomes were evaluation of the need for invasive mechanical ventilator (IMV) support, the need for intensive care unit (ICU) care and death. All outcomes were measured as dichotomous variables. RESULTS: A total of 28 observational studies, covering data from 63,537 individuals with COVID-19, were included. The use of statins was significantly associated with decreased mortality (odds ratio [OR] = 0.71, 95% confidence interval [CI]: 0.55-0.92, I2=72%) and the need for IMV (OR = 0.81, 95% CI: 0.69-0.95, I2=0%) but was not linked to the need for ICU care (OR = 0.91, 95% CI: 0.55-1.51, I2=66%). Subgroup analysis further identified five types of studies in which statin users had even lower odds of death. CONCLUSIONS: The use of statins was significantly associated with a reduced need for IMV and decreased mortality among individuals with COVID-19. Statins may not need to be discontinued because of concern for COVID-19 on admission. Further randomized controlled trial (RCTs) are needed to clarify the causal effect between statin use and severe COVID-19 outcomes.Key messagesParticipants in five types of studies were shown to have even lower odds of death when taking statins.The use of statins was significantly associated with a reduced need for invasive mechanical ventilation and decreased all-cause mortality among individuals with COVID-19. However, statin use did not prevent participants from needing care in the intensive care unit.The results justify performing randomized controlled trials (RCTs) to validate the benefits of statins on COVID-19 outcomes.


Assuntos
COVID-19/mortalidade , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Respiração Artificial/estatística & dados numéricos , COVID-19/terapia , Doenças Cardiovasculares/tratamento farmacológico , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Ensaios Clínicos Controlados Aleatórios como Assunto
6.
Curr Cardiol Rep ; 23(7): 75, 2021 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-34081215

RESUMO

PURPOSE OF REVIEW: This review summarizes recent cardiovascular outcome trials (CVOTs) with glucose-lowering drugs. RECENT FINDINGS: The majority of recent CVOTs with glucose-lowering drugs have tested dipeptidyl peptidase-4 inhibitors (DPP4-i), glucagon-like peptide-1 receptors agonists (GLP1-RA), and sodium-glucose cotransporter 2 inhibitors (SGLT2i), but studies have also been performed with other agents including thiazolidinediones and insulin. All CVOTs with DPP4-I, GLP1-RA, and SGLT2-i have demonstrated the cardiovascular (CV) safety of these agents compared to usual care. However, certain GLP1-RAs (liraglutide, subcutaneous semaglutide, albiglutide, dulaglutide) and SGLT2-i (empagliflozin, canagliflozin) have demonstrated a CV benefit, showing significant reductions in composite cardiovascular outcomes. Furthermore, all SGLT2-i also significantly decreased the risk for hospitalization for heart failure. Results from these studies have altered clinical guidelines worldwide and have resulted in new indications for some glucose-lowering drugs. In patients with T2D and high risk for CVD, GLP-1RA or SGLT2-i with proven cardiovascular benefit are recommended, irrespective of glycemic control.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Preparações Farmacêuticas , Inibidores do Transportador 2 de Sódio-Glicose , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus Tipo 2/tratamento farmacológico , Glucose , Humanos , Hipoglicemiantes/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico
7.
Int J Mol Sci ; 22(11)2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-34071276

RESUMO

Cardiovascular disease is the leading cause of death worldwide, and its prevalence is increasing due to the aging of societies. Atherosclerosis, a type of chronic inflammatory disease that occurs in arteries, is considered to be the main cause of cardiovascular diseases such as ischemic heart disease or stroke. In addition, the inflammatory response caused by atherosclerosis confers a significant effect on chronic inflammatory diseases such as psoriasis and rheumatic arthritis. Here, we review the mechanism of action of the main causes of atherosclerosis such as plasma LDL level and inflammation; furthermore, we review the recent findings on the preclinical and clinical effects of antibodies that reduce the LDL level and those that neutralize the cytokines involved in inflammation. The apolipoprotein B autoantibody and anti-PCSK9 antibody reduced the level of LDL and plaques in animal studies, but failed to significantly reduce carotid inflammation plaques in clinical trials. The monoclonal antibodies against PCSK9 (alirocumab, evolocumab), which are used as a treatment for hyperlipidemia, lowered cholesterol levels and the incidence of cardiovascular diseases. Antibodies that neutralize inflammatory cytokines (TNF-α, IL-1ß, IL-6, IL-17, and IL-12/23) have shown promising but contradictory results and thus warrant further research.


Assuntos
Anticorpos/farmacologia , Aterosclerose/tratamento farmacológico , Doenças Cardiovasculares/tratamento farmacológico , Imunização Passiva/métodos , Animais , Anticorpos/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Anticolesterolemiantes/uso terapêutico , Apolipoproteínas B , Autoanticorpos , LDL-Colesterol/sangue , Citocinas/imunologia , Humanos , Inflamação/tratamento farmacológico , Fragmentos de Peptídeos , Pró-Proteína Convertase 9/efeitos dos fármacos , Acidente Vascular Cerebral/tratamento farmacológico
8.
Molecules ; 26(10)2021 May 11.
Artigo em Inglês | MEDLINE | ID: covidwho-1224076

RESUMO

Resveratrol is a phytoalexin produced by many plants as a defense mechanism against stress-inducing conditions. The richest dietary sources of resveratrol are berries and grapes, their juices and wines. Good bioavailability of resveratrol is not reflected in its high biological activity in vivo because of resveratrol isomerization and its poor solubility in aqueous solutions. Proteins, cyclodextrins and nanomaterials have been explored as innovative delivery vehicles for resveratrol to overcome this limitation. Numerous in vitro and in vivo studies demonstrated beneficial effects of resveratrol in cardiovascular diseases (CVD). Main beneficial effects of resveratrol intake are cardioprotective, anti-hypertensive, vasodilatory, anti-diabetic, and improvement of lipid status. As resveratrol can alleviate the numerous factors associated with CVD, it has potential as a functional supplement to reduce COVID-19 illness severity in patients displaying poor prognosis due to cardio-vascular complications. Resveratrol was shown to mitigate the major pathways involved in the pathogenesis of SARS-CoV-2 including regulation of the renin-angiotensin system and expression of angiotensin-converting enzyme 2, stimulation of immune system and downregulation of pro-inflammatory cytokine release. Therefore, several studies already have anticipated potential implementation of resveratrol in COVID-19 treatment. Regular intake of a resveratrol rich diet, or resveratrol-based complementary medicaments, may contribute to a healthier cardio-vascular system, prevention and control of CVD, including COVID-19 disease related complications of CVD.


Assuntos
COVID-19/tratamento farmacológico , Doenças Cardiovasculares , Resveratrol , SARS-CoV-2/metabolismo , Disponibilidade Biológica , COVID-19/complicações , COVID-19/metabolismo , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/metabolismo , Humanos , Resveratrol/farmacocinética , Resveratrol/uso terapêutico
9.
Pharmacol Rev ; 73(3): 924-967, 2021 07.
Artigo em Inglês | MEDLINE | ID: covidwho-1258994

RESUMO

The endothelium, a cellular monolayer lining the blood vessel wall, plays a critical role in maintaining multiorgan health and homeostasis. Endothelial functions in health include dynamic maintenance of vascular tone, angiogenesis, hemostasis, and the provision of an antioxidant, anti-inflammatory, and antithrombotic interface. Dysfunction of the vascular endothelium presents with impaired endothelium-dependent vasodilation, heightened oxidative stress, chronic inflammation, leukocyte adhesion and hyperpermeability, and endothelial cell senescence. Recent studies have implicated altered endothelial cell metabolism and endothelial-to-mesenchymal transition as new features of endothelial dysfunction. Endothelial dysfunction is regarded as a hallmark of many diverse human panvascular diseases, including atherosclerosis, hypertension, and diabetes. Endothelial dysfunction has also been implicated in severe coronavirus disease 2019. Many clinically used pharmacotherapies, ranging from traditional lipid-lowering drugs, antihypertensive drugs, and antidiabetic drugs to proprotein convertase subtilisin/kexin type 9 inhibitors and interleukin 1ß monoclonal antibodies, counter endothelial dysfunction as part of their clinical benefits. The regulation of endothelial dysfunction by noncoding RNAs has provided novel insights into these newly described regulators of endothelial dysfunction, thus yielding potential new therapeutic approaches. Altogether, a better understanding of the versatile (dys)functions of endothelial cells will not only deepen our comprehension of human diseases but also accelerate effective therapeutic drug discovery. In this review, we provide a timely overview of the multiple layers of endothelial function, describe the consequences and mechanisms of endothelial dysfunction, and identify pathways to effective targeted therapies. SIGNIFICANCE STATEMENT: The endothelium was initially considered to be a semipermeable biomechanical barrier and gatekeeper of vascular health. In recent decades, a deepened understanding of the biological functions of the endothelium has led to its recognition as a ubiquitous tissue regulating vascular tone, cell behavior, innate immunity, cell-cell interactions, and cell metabolism in the vessel wall. Endothelial dysfunction is the hallmark of cardiovascular, metabolic, and emerging infectious diseases. Pharmacotherapies targeting endothelial dysfunction have potential for treatment of cardiovascular and many other diseases.


Assuntos
Aterosclerose , COVID-19 , Fármacos Cardiovasculares , Doenças Cardiovasculares , Endotélio Vascular , Aterosclerose/tratamento farmacológico , Aterosclerose/metabolismo , Aterosclerose/fisiopatologia , COVID-19/tratamento farmacológico , COVID-19/metabolismo , COVID-19/fisiopatologia , Fármacos Cardiovasculares/classificação , Fármacos Cardiovasculares/farmacologia , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/fisiopatologia , Descoberta de Drogas , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Endotélio Vascular/fisiopatologia , Humanos , Terapia de Alvo Molecular/métodos , Terapia de Alvo Molecular/tendências , SARS-CoV-2
10.
Ann Med ; 53(1): 874-884, 2021 12.
Artigo em Inglês | MEDLINE | ID: covidwho-1258660

RESUMO

BACKGROUND: Statins are widely used to treat people with metabolic and cardiovascular disorders. The effect of statins on coronavirus disease 2019 (COVID-19) is unclear. To investigate the association between statins and COVID-19 outcomes and, if possible, identify the subgroup population that benefits most from statin use. MATERIALS AND METHODS: A systematic review and meta-analysis of published studies that included statin users and described COVID-19 outcomes through 10 November 2020. This study used the generic inverse variance method to perform meta-analyses with random-effects modelling. The main outcomes were evaluation of the need for invasive mechanical ventilator (IMV) support, the need for intensive care unit (ICU) care and death. All outcomes were measured as dichotomous variables. RESULTS: A total of 28 observational studies, covering data from 63,537 individuals with COVID-19, were included. The use of statins was significantly associated with decreased mortality (odds ratio [OR] = 0.71, 95% confidence interval [CI]: 0.55-0.92, I2=72%) and the need for IMV (OR = 0.81, 95% CI: 0.69-0.95, I2=0%) but was not linked to the need for ICU care (OR = 0.91, 95% CI: 0.55-1.51, I2=66%). Subgroup analysis further identified five types of studies in which statin users had even lower odds of death. CONCLUSIONS: The use of statins was significantly associated with a reduced need for IMV and decreased mortality among individuals with COVID-19. Statins may not need to be discontinued because of concern for COVID-19 on admission. Further randomized controlled trial (RCTs) are needed to clarify the causal effect between statin use and severe COVID-19 outcomes.Key messagesParticipants in five types of studies were shown to have even lower odds of death when taking statins.The use of statins was significantly associated with a reduced need for invasive mechanical ventilation and decreased all-cause mortality among individuals with COVID-19. However, statin use did not prevent participants from needing care in the intensive care unit.The results justify performing randomized controlled trials (RCTs) to validate the benefits of statins on COVID-19 outcomes.


Assuntos
COVID-19/mortalidade , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Respiração Artificial/estatística & dados numéricos , COVID-19/terapia , Doenças Cardiovasculares/tratamento farmacológico , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Ensaios Clínicos Controlados Aleatórios como Assunto
11.
Sci Rep ; 11(1): 12414, 2021 06 14.
Artigo em Inglês | MEDLINE | ID: covidwho-1268007

RESUMO

Primary aim was to assess prevalence and severity of potential and real drug-drug interactions (DDIs) among therapies for COVID-19 and concomitant medications in hospitalized patients with confirmed SARS-CoV-2 infection. The secondary aim was to analyze factors associated with rDDIs. An observational single center cohort study conducted at a tertiary hospital in Spain from March 1st to April 30th. rDDIs refer to interaction with concomitant drugs prescribed during hospital stay whereas potential DDIs (pDDIs) refer to those with domiciliary medication. DDIs checked with The University of Liverpool resource. Concomitant medications were categorized according to the Anatomical Therapeutic Chemical classification system. Binomial logistic regression was carried out to identify factors associated with rDDIs. A total of 174 patients were analyzed. DDIs were detected in 152 patients (87.4%) with a total of 417 rDDIs between COVID19-related drugs and involved hospital concomitant medication (60 different drugs) while pDDIs were detected in 105 patients (72.9%) with a total of 553 pDDIs. From all 417 rDDIs, 43.2% (n = 180) were associated with lopinavir/ritonavir and 52.9% (n = 221) with hydroxychloroquine, both of them the most prescribed (106 and 165 patients, respectively). The main mechanism of interaction observed was QTc prolongation. Clinically relevant rDDIs were identified among 81.1% (n = 338) ('potential interactions') and 14.6% (n = 61) (contraindicated) of the patients. Charlson index (OR 1.34, 95% IC 1.02-1.76) and number of drugs prescribed during admission (OR 1.42, 95% IC 1.12-1.81) were independently associated with rDDIs. Prevalence of patients with real and pDDIs was high, especially those clinically relevant. Both comorbidities and polypharmacy were found as risk factors independently associated with DDIs development.


Assuntos
COVID-19/tratamento farmacológico , Interações Medicamentosas , Hidroxicloroquina/química , Lopinavir/química , Ritonavir/química , Idoso , Analgésicos/química , Analgésicos/uso terapêutico , COVID-19/patologia , COVID-19/virologia , Doenças Cardiovasculares/tratamento farmacológico , Estudos de Coortes , Diuréticos/química , Diuréticos/uso terapêutico , Feminino , Humanos , Hidroxicloroquina/uso terapêutico , Lopinavir/uso terapêutico , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/tratamento farmacológico , Polimedicação , Fatores de Risco , Ritonavir/uso terapêutico , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de Doença , Espanha
12.
Curr Opin Lipidol ; 32(4): 231-243, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-34116544

RESUMO

PURPOSE OF REVIEW: Coronavirus Disease 2019 (COVID19) has caused significant global morbidity and mortality, especially in persons with underlying cardiovascular disease. There have been concerns that lipid-lowering therapy (LLT) increases angiotensin-converting enzyme 2 levels. Conversely, pleiotropic effects of statins can theoretically protect against severe COVID19 infection, supporting evidence from other respiratory illnesses in which statin use probably confers benefit. RECENT FINDINGS: There is an abundance of studies that show that statins are safe and potentially protect against severe COVID19 infection (critical illness and death), even when adjustment for potential confounders is undertaken. However, the evidence is limited to retrospective cohorts. The benefit for patients with diabetes is less clear. There is a paucity of evidence for other LLT agents. Available clinical guidelines recommend the ongoing use of LLT in patients with COVID19 (unless specifically contra-indicated) and the data from available studies support these. SUMMARY: In patients with COVID19 infection, LLT should be continued. However, the current findings need substantiating in larger prospective clinical studies with specific examination of the possible mechanisms by which LLT confers benefit from COVID19.


Assuntos
Aterosclerose/tratamento farmacológico , COVID-19/tratamento farmacológico , Doenças Cardiovasculares/tratamento farmacológico , Dislipidemias/tratamento farmacológico , Aterosclerose/complicações , Aterosclerose/epidemiologia , Aterosclerose/virologia , COVID-19/complicações , COVID-19/epidemiologia , COVID-19/virologia , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/virologia , LDL-Colesterol/efeitos dos fármacos , Dislipidemias/complicações , Dislipidemias/epidemiologia , Dislipidemias/virologia , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipolipemiantes/uso terapêutico , SARS-CoV-2/patogenicidade
13.
Molecules ; 26(10)2021 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-34064568

RESUMO

Resveratrol is a phytoalexin produced by many plants as a defense mechanism against stress-inducing conditions. The richest dietary sources of resveratrol are berries and grapes, their juices and wines. Good bioavailability of resveratrol is not reflected in its high biological activity in vivo because of resveratrol isomerization and its poor solubility in aqueous solutions. Proteins, cyclodextrins and nanomaterials have been explored as innovative delivery vehicles for resveratrol to overcome this limitation. Numerous in vitro and in vivo studies demonstrated beneficial effects of resveratrol in cardiovascular diseases (CVD). Main beneficial effects of resveratrol intake are cardioprotective, anti-hypertensive, vasodilatory, anti-diabetic, and improvement of lipid status. As resveratrol can alleviate the numerous factors associated with CVD, it has potential as a functional supplement to reduce COVID-19 illness severity in patients displaying poor prognosis due to cardio-vascular complications. Resveratrol was shown to mitigate the major pathways involved in the pathogenesis of SARS-CoV-2 including regulation of the renin-angiotensin system and expression of angiotensin-converting enzyme 2, stimulation of immune system and downregulation of pro-inflammatory cytokine release. Therefore, several studies already have anticipated potential implementation of resveratrol in COVID-19 treatment. Regular intake of a resveratrol rich diet, or resveratrol-based complementary medicaments, may contribute to a healthier cardio-vascular system, prevention and control of CVD, including COVID-19 disease related complications of CVD.


Assuntos
COVID-19/tratamento farmacológico , Doenças Cardiovasculares , Resveratrol , SARS-CoV-2/metabolismo , Disponibilidade Biológica , COVID-19/complicações , COVID-19/metabolismo , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/metabolismo , Humanos , Resveratrol/farmacocinética , Resveratrol/uso terapêutico
14.
Vnitr Lek ; 67(2): 119-124, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34074111

RESUMO

Blockade of the renin angiotensin aldosterone system (RAAS) is currently considered to be the gold standard of antihypertensive therapy. ACE inhibitors and AT1-blockers are clinically the most relevant groups of RAAS blockers. Even though both drug groups block angiotensin II, ACE inhibitors typically reduce the degradation of bradykinin, which leads to the release of nitric oxide and prostaglandins with subsequent vasodilation. These differences in the mechanism of action can be of clinical relevance for hypertensive patients. Morbidity mortality studies of RAAS blockers have been reported in which ACE inhibitors, particularly perindopril, improved the overall survival in hypertensive patients. In the ONTARGET trial, a direct comparison of both drug groups yielded comparable results. Perindopril, which has been used in the clinical practice for more than 25 years, is a long-acting lipophilic angiotensin-converting enzyme inhibitor with a once-daily dosage schedule and a high affinity to tissue-converting enzyme. Its safety, efficacy, and very good tolerance have been shown in a number of studies. It is part of many fixed combinations which improve patient compliance and increase the effect of treatment of cardiovascular diseases.


Assuntos
Doenças Cardiovasculares , Hipertensão , Inibidores da Enzima Conversora de Angiotensina , Anti-Hipertensivos/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , Humanos , Hipertensão/tratamento farmacológico , Perindopril , Sistema Renina-Angiotensina
15.
Pharmacol Rev ; 73(3): 924-967, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34088867

RESUMO

The endothelium, a cellular monolayer lining the blood vessel wall, plays a critical role in maintaining multiorgan health and homeostasis. Endothelial functions in health include dynamic maintenance of vascular tone, angiogenesis, hemostasis, and the provision of an antioxidant, anti-inflammatory, and antithrombotic interface. Dysfunction of the vascular endothelium presents with impaired endothelium-dependent vasodilation, heightened oxidative stress, chronic inflammation, leukocyte adhesion and hyperpermeability, and endothelial cell senescence. Recent studies have implicated altered endothelial cell metabolism and endothelial-to-mesenchymal transition as new features of endothelial dysfunction. Endothelial dysfunction is regarded as a hallmark of many diverse human panvascular diseases, including atherosclerosis, hypertension, and diabetes. Endothelial dysfunction has also been implicated in severe coronavirus disease 2019. Many clinically used pharmacotherapies, ranging from traditional lipid-lowering drugs, antihypertensive drugs, and antidiabetic drugs to proprotein convertase subtilisin/kexin type 9 inhibitors and interleukin 1ß monoclonal antibodies, counter endothelial dysfunction as part of their clinical benefits. The regulation of endothelial dysfunction by noncoding RNAs has provided novel insights into these newly described regulators of endothelial dysfunction, thus yielding potential new therapeutic approaches. Altogether, a better understanding of the versatile (dys)functions of endothelial cells will not only deepen our comprehension of human diseases but also accelerate effective therapeutic drug discovery. In this review, we provide a timely overview of the multiple layers of endothelial function, describe the consequences and mechanisms of endothelial dysfunction, and identify pathways to effective targeted therapies. SIGNIFICANCE STATEMENT: The endothelium was initially considered to be a semipermeable biomechanical barrier and gatekeeper of vascular health. In recent decades, a deepened understanding of the biological functions of the endothelium has led to its recognition as a ubiquitous tissue regulating vascular tone, cell behavior, innate immunity, cell-cell interactions, and cell metabolism in the vessel wall. Endothelial dysfunction is the hallmark of cardiovascular, metabolic, and emerging infectious diseases. Pharmacotherapies targeting endothelial dysfunction have potential for treatment of cardiovascular and many other diseases.


Assuntos
Aterosclerose , COVID-19 , Fármacos Cardiovasculares , Doenças Cardiovasculares , Endotélio Vascular , Aterosclerose/tratamento farmacológico , Aterosclerose/metabolismo , Aterosclerose/fisiopatologia , COVID-19/tratamento farmacológico , COVID-19/metabolismo , COVID-19/fisiopatologia , Fármacos Cardiovasculares/classificação , Fármacos Cardiovasculares/farmacologia , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/fisiopatologia , Descoberta de Drogas , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Endotélio Vascular/fisiopatologia , Humanos , Terapia de Alvo Molecular/métodos , Terapia de Alvo Molecular/tendências , SARS-CoV-2
16.
BMC Geriatr ; 21(1): 366, 2021 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-34134649

RESUMO

BACKGROUND: Overtreatment with cardiometabolic medication in older patients can lead to major adverse events. Timely deprescribing of these medications is therefore essential. Self-reported willingness to stop medication is usually high among older people, still overtreatment with cardiometabolic medication is common and deprescribing is rarely initiated. An important barrier for deprescribing reported by general practitioners is the patients' unwillingness to stop the medication. More insights are needed into the influence of patients' characteristics on their attitudes towards deprescribing and differences in these attitudes between cardiometabolic medication groups. METHODS: A survey in older people using cardiometabolic medication using the revised Patients' Attitudes Towards Deprescribing (rPATD) questionnaire was performed. Participants completed the general rPATD and an adapted version for four medication groups. Linear and ordinal logistic regression were used to assess the influence of age, sex, therapeutic area and number of medications used on the patients' general attitudes towards deprescribing. Univariate analysis was used to compare differences in deprescribing attitudes towards sulfonylureas, insulins, antihypertensive medication and statins. RESULTS: Overall, 314 out of 1143 invited participants completed the survey (median age 76 years, 54% female). Most participants (80%) were satisfied with their medication and willing to stop medications if their doctor said it was possible (88%). Age, sex and therapeutic area had no influence on the general attitudes towards deprescribing. Taking more than ten medicines was significantly associated with a higher perceived medication burden. Antihypertensive medication and insulin were considered more appropriate than statins, and insulin was considered more appropriate than sulfonylureas not favouring deprescribing. CONCLUSIONS: The majority of older people using cardiometabolic medication are willing to stop one of their medicines if their doctor said it was possible. Health care providers should take into account that patients perceive some of their medication as more appropriate than other medication when discussing deprescribing.


Assuntos
Doenças Cardiovasculares , Desprescrições , Idoso , Atitude , Doenças Cardiovasculares/tratamento farmacológico , Feminino , Humanos , Masculino , Polimedicação , Inquéritos e Questionários
17.
Clin Interv Aging ; 16: 1047-1056, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34135577

RESUMO

Purpose: Medication therapy is crucial in the management of chronic coronary syndrome (CCS). The use of potentially inappropriate medications (PIMs) contributes to poor outcomes in older patients, making it a major public health concern. However, few studies are available on PIMs use in older Chinese CCS patients. To investigate the frequency of prescribed PIMs at discharge and explore risk factors in older adults with CCS. Patients and Methods: The cross-sectional study was conducted in a tertiary hospital in China over three months, from 1st October to 31st December, 2019. CCS patients aged over 60 years who were discharged alive were recruited. Information on demographics and medications at discharge was collected. Clinical data including diagnoses, frailty status, New York Heart Association (NYHA) class and age-adjusted Charlson Comorbidity Index (ACCI) were evaluated in each patient. PIMs were identified using the 2019 Beers criteria. Binary logistic regression was performed to recognize variables related to PIMs. Results: A total of 447 eligible patients with 2947 medications were included. The prevalence of PIMs use was 38%. Medications to be avoided, to be used with caution, and with drug-drug interactions were 38.4%, 48.9% and 12.7% of the PIMs, respectively. Medications with drug-disease/syndrome interactions and those adjusted for kidney function were not identified. The common PIMs were diuretics (37.1%), benzodiazepines and benzodiazepine receptor agonist hypnotics (15.2%), glimepiride (13.1%), and co-prescription of potassium-sparing diuretics and renin-angiotensin system (RAS) inhibitors (9.7%). Individuals with frailty syndrome, polypharmacy, multiple comorbidities, atrial fibrillation, psychiatric disorders and greater NYHA class severity were more likely to receive PIMs. Conclusion: Prescription of PIMs was a common burden in older adults. A CCS multidisciplinary team is needed to control PIMs, especially in vulnerable older patients.


Assuntos
Anti-Hipertensivos/efeitos adversos , Doenças Cardiovasculares/tratamento farmacológico , Idoso Fragilizado/estatística & dados numéricos , Prescrição Inadequada/efeitos adversos , Lista de Medicamentos Potencialmente Inapropriados/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Anti-Hipertensivos/uso terapêutico , Pequim , Doenças Cardiovasculares/epidemiologia , Estudos Transversais , Humanos , Prescrição Inadequada/estatística & dados numéricos , Modelos Logísticos , Masculino , Alta do Paciente/estatística & dados numéricos , Polimedicação , Prevalência , Fatores de Risco , Centros de Atenção Terciária
18.
Sci Rep ; 11(1): 12414, 2021 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-34127740

RESUMO

Primary aim was to assess prevalence and severity of potential and real drug-drug interactions (DDIs) among therapies for COVID-19 and concomitant medications in hospitalized patients with confirmed SARS-CoV-2 infection. The secondary aim was to analyze factors associated with rDDIs. An observational single center cohort study conducted at a tertiary hospital in Spain from March 1st to April 30th. rDDIs refer to interaction with concomitant drugs prescribed during hospital stay whereas potential DDIs (pDDIs) refer to those with domiciliary medication. DDIs checked with The University of Liverpool resource. Concomitant medications were categorized according to the Anatomical Therapeutic Chemical classification system. Binomial logistic regression was carried out to identify factors associated with rDDIs. A total of 174 patients were analyzed. DDIs were detected in 152 patients (87.4%) with a total of 417 rDDIs between COVID19-related drugs and involved hospital concomitant medication (60 different drugs) while pDDIs were detected in 105 patients (72.9%) with a total of 553 pDDIs. From all 417 rDDIs, 43.2% (n = 180) were associated with lopinavir/ritonavir and 52.9% (n = 221) with hydroxychloroquine, both of them the most prescribed (106 and 165 patients, respectively). The main mechanism of interaction observed was QTc prolongation. Clinically relevant rDDIs were identified among 81.1% (n = 338) ('potential interactions') and 14.6% (n = 61) (contraindicated) of the patients. Charlson index (OR 1.34, 95% IC 1.02-1.76) and number of drugs prescribed during admission (OR 1.42, 95% IC 1.12-1.81) were independently associated with rDDIs. Prevalence of patients with real and pDDIs was high, especially those clinically relevant. Both comorbidities and polypharmacy were found as risk factors independently associated with DDIs development.


Assuntos
COVID-19/tratamento farmacológico , Interações Medicamentosas , Hidroxicloroquina/química , Lopinavir/química , Ritonavir/química , Idoso , Analgésicos/química , Analgésicos/uso terapêutico , COVID-19/patologia , COVID-19/virologia , Doenças Cardiovasculares/tratamento farmacológico , Estudos de Coortes , Diuréticos/química , Diuréticos/uso terapêutico , Feminino , Humanos , Hidroxicloroquina/uso terapêutico , Lopinavir/uso terapêutico , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/tratamento farmacológico , Polimedicação , Fatores de Risco , Ritonavir/uso terapêutico , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de Doença , Espanha
19.
Medicina (Kaunas) ; 57(6)2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-34071454

RESUMO

Background and Objectives: Cardiovascular disease (CVD) is the leading cause of death globally and hypercholesterolemia is one of the major risk factors associated with CVD. Due to a growing body of research on side effects and long-term impacts of conventional CVD treatments, focus is shifting towards exploring alternative treatment approaches such as Ayurveda. However, because of a lack of strong scientific evidence, the safety and efficacy profiles of such interventions have not been well established. The current study aims to conduct a systematic review and meta-analyses to explore the strength of evidence on efficacy and safety of Ayurvedic herbs for hypercholesterolemia. Methods: Literature searches were conducted using databases including Medline, Cochrane Database, AMED, Embase, AYUSH research portal, and many others. All randomized controlled trials on individuals with hypercholesterolemia using Ayurvedic herbs (alone or in combination) with an exposure period of ≥ 3 weeks were included, with primary outcomes being total cholesterol levels, adverse events, and other cardiovascular events. The search strategy was determined with the help of the Cochrane Metabolic and Endocrine Disorders Group. Two researchers assessed the risk of each study individually and discrepancies were resolved by consensus or consultation with a third researcher. Meta-analysis was conducted using the inverse variance method and results are presented as forest plots and data summary tables using Revman v5.3. Results: A systematic review of 32 studies with 1386 participants found randomized controlled trials of three Ayurvedic herbs, Allium sativum (garlic), Commiphora mukul (guggulu), and Nigella sativa (black cumin) on hypercholesterolemia that met inclusion criteria. The average duration of intervention was 12 weeks. Meta-analysis of the trials showed that guggulu reduced total cholesterol and low-density lipoprotein levels by 16.78 mg/dL (95% C.I. 13.96 to 2.61; p-value = 0.02) and 18.78 mg/dL (95% C.I. 34.07 to 3.48; p = 0.02), respectively. Garlic reduced LDL-C by 10.37 mg/dL (95% C.I. -17.58 to -3.16; p-value = 0.005). Black cumin lowered total cholesterol by 9.28 mg/dL (95% C.I. -17.36, to -1.19, p-value = 0.02). Reported adverse side effects were minimal. Conclusion: There is moderate to high level of evidence from randomized controlled trials that the Ayurvedic herbs guggulu, garlic, and black cumin are moderately effective for reducing hypercholesterolemia. In addition, minimal evidence was found for any side effects associated with these herbs, positioning them as safe adjuvants to conventional treatments.


Assuntos
Doenças Cardiovasculares , Alho , Hipercolesterolemia , Hiperlipidemias , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/prevenção & controle , Humanos , Hipercolesterolemia/tratamento farmacológico , Medicina Ayurvédica
20.
Food Funct ; 12(9): 3799-3819, 2021 May 11.
Artigo em Inglês | MEDLINE | ID: covidwho-1223115

RESUMO

Tea is one of the most consumed beverages around the world and as such, it is constantly the object of novel research. This review focuses on the research performed during the last five years to provide an updated view of the current position of tea regarding human health. According to most authors, tea health benefits can be traced back to its bioactive components, mostly phenolic compounds. Among them, catechins are the most abundant. Tea has an important antioxidant capacity and anti-inflammatory properties, which make this beverage (or its extracts) a potential aid in the fight against several chronic diseases. On the other hand, some studies report the possibility of toxic effects and it is advisable to reduce tea consumption, such as in the last trimester of pregnancy. Additionally, new technologies are increasing researchers' possibilities to study the effect of tea on human gut microbiota and even against SARS CoV-2. This beverage favours some beneficial gut microbes, which could have important repercussions due to the influence of gut microbiota on human health.


Assuntos
Comportamentos Relacionados com a Saúde , Extratos Vegetais/farmacologia , Chá , Antioxidantes/análise , Bebidas/análise , Doenças Cardiovasculares/tratamento farmacológico , Catequina/análise , Humanos , Hipertensão/tratamento farmacológico , Obesidade/tratamento farmacológico , Fenóis/análise , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/química
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...