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1.
Stud Health Technol Inform ; 264: 1712-1713, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31438306

RESUMO

We developed a HeartGuardian app and explored its effects supporting people with CVD on lipid control and medication adherence. Fifty-seven patients were enrolled, 29 in the intervention group and 28 in the control group. The 12-week intervention resulted in a moderate improvement in lipid level and greater improvement in medication adherence (82.14% vs 37.93%, P = 0.001). These outcomes translate into significant differences in occurrence of major adverse cardiac events (28.75% vs 72.43%, P = 0.001).


Assuntos
Doenças Cardiovasculares , Prevenção Secundária , Smartphone , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/prevenção & controle , Humanos , Adesão à Medicação
2.
Int Heart J ; 60(4): 910-918, 2019 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-31308328

RESUMO

Previous studies have provided established evidence on adverse outcomes of the coadministration of proton pump inhibitors (PPIs) and clopidogrel, whereas cerebro-cardiovascular outcomes of PPI use in the absence of clopidogrel therapy remain controversial.In this study, we aimed to assess the association between PPIs and cerebro-cardiovascular outcomes independent of clopidogrel.Systematic searches were conducted in the Cochrane Library, PubMed, and Embase databases for all relevant studies up to August 2018. Odds ratios (ORs) with its 95% confidence intervals (CIs) were abstracted and pooled using the random-effects model.A total of 14 observational studies (13 cohort studies and 1 case-control study) were identified. Compared with non-PPI users, PPI users experienced higher risks of stroke (OR: 1.22, 95% CI: 1.08-1.36), myocardial infarction (MI; OR: 1.23, 95% CI: 1.14-1.32), cardiovascular death (OR: 1.83, 95% CI: 1.69-1.98), and major adverse cardiovascular events (MACEs; OR: 1.22, 95% CI: 1.05-1.40) independent of clopidogrel use, but not all-cause death (OR: 1.50, 95% CI: 0.99-2.25). In the subgroup analysis, PPI alone was associated with significant risks of new-onset MI (OR: 1.23, 95% CI: 1.13-1.35) and stroke (OR: 1.17, 95% CI: 1.05-1.30) in patients without previous MI or stoke and recurrent MI (OR: 1.24, 95% CI: 1.02-1.51) and stroke (OR: 1.36, 95% CI: 1.19-1.55) risks in patients with a previous MI.Based on current publications, PPI use seems to be associated with increased risks of stroke, MI, cardiovascular death, and MACEs independent of clopidogrel. Greater caution should be therefore exercised while considering its clinical benefits and further investigate any causal relationships.


Assuntos
Doenças Cardiovasculares/tratamento farmacológico , Transtornos Cerebrovasculares/tratamento farmacológico , Clopidogrel/farmacologia , Inibidores da Bomba de Prótons/farmacologia , Doenças Cardiovasculares/mortalidade , Causas de Morte/tendências , Transtornos Cerebrovasculares/mortalidade , Saúde Global , Humanos , Estudos Observacionais como Assunto , Inibidores da Agregação de Plaquetas/farmacologia , Fatores de Risco , Taxa de Sobrevida/tendências
3.
Expert Opin Ther Pat ; 29(7): 555-578, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31204543

RESUMO

INTRODUCTION: Human neutrophil elastase (HNE) is involved in a variety of serious chronic diseases, especially cardiopulmonary pathologies. For this reason, the regulation of HNE activity represents a promising therapeutic approach, which is evident by the development of a number of new and selective HNE inhibitors, both in the academic and pharmaceutical environments. AREAS COVERED: The present review analyzes and summarizes the patent literature regarding human neutrophil elastase inhibitors for the treatment of cardiopulmonary diseases over 2014-2018. EXPERT OPINION: HNE is an interesting and defined target to treat various inflammatory diseases, including a number of cardiopulmonary pathologies. The research in this field is quite active, and a number of HNE inhibitors are currently in various stages of clinical development. In addition, new opportunities for HNE inhibitor development stem from recent studies demonstrating the involvement of HNE in many other inflammatory pathologies, including rheumatoid arthritis, inflammatory bowel disease, skin diseases, and cancer. Furthermore, the development of dual HNE/proteinase 3 inhibitors is being pursued as an innovative approach for the treatment of neutrophilic inflammatory diseases. Thus, these new developments will likely stimulate new and increased interest in this important therapeutic target and for the development of novel and selective HNE inhibitors.


Assuntos
Desenvolvimento de Medicamentos/métodos , Elastase de Leucócito/efeitos dos fármacos , Proteínas Secretadas Inibidoras de Proteinases/farmacologia , Animais , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/enzimologia , Doenças Cardiovasculares/fisiopatologia , Humanos , Inflamação/tratamento farmacológico , Inflamação/fisiopatologia , Elastase de Leucócito/metabolismo , Pneumopatias/tratamento farmacológico , Pneumopatias/enzimologia , Pneumopatias/fisiopatologia , Patentes como Assunto
4.
Ter Arkh ; 91(4): 90-98, 2019 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-31094482

RESUMO

AIM: The aim of the study was to assess cardiovascular risk in patients with elevated levels of total cholesterol and LDL-C and concomitant AH, a comparative analysis of adherence, efficacy and safety of various forms of combined therapy in outpatient practice, including promising lisinopril/amlodipine/rosuvastatin FC (Ekvamer®). MATERIALS AND METHODS: The ANICHKOV study included 702 patients in Moscow and the Moscow region over 18 years old with a -chole-sterol level ≥7.5 mmol/l and/or LDL-C ≥4.9 mmol/l from March 2017 to December 2018 based on 2 federal centers. According to the results of visit I, patients were prescribed with one of three therapy schemes. In the absence of AH, patients received scheme I -(Mertenil® at initial dosage of 10 mg/day). When history of AH existed or AH detected at visit I, patients were randomized to scheme II (Ekvamer® 5/10/10 mg/day) or III (Mertenil® 10 mg/day + Ekvator® 5/10 mg/day). During the observation, the treatment scheme remained unchanged, however, if the target levels of LDL-C and/or BP were not reached, the doses could be increased. The analysis of the main effects of the prescribed therapy were carried out for 12 months, and the frequency of MACE (CVD, ACS, stroke, or hospitalization to perform PCI) was also evaluated. RESULTS: Following the visit I, scheme I was assigned to 390 patients (55.6%), scheme II - 190 (27.1%), scheme III - 122 (17.4%). In 147 patients (20.9%), TG level was >2.3 mmol/l, which required additional fenofibrate intake in a dose of 145 mg/day. Adherence level was 89.5%, including scheme I - 91.7%, scheme II - 90.5%, scheme III - only 81.8%. In general, among compliant patients (n = 590), the decrease in TCh level was 41.0%, LDL-C - 47.4%. 16.6% of patients reached target levels of LDL-C <2.5 mmol/l, 5.6% - <1.8 mmol/l. In the fenofibrate subgroup, TG level decrease was 34.6%. During the follow-up period, 47 cases of side effects were observed in 27 patients (4.6%), that did not require modification of therapy. Systolic BP reduction in compliant patients of schemes II and III was 20 mm. Hg (13.1%), diastolic BP - 12 mm. Hg (13.6%), target BP levels (<140/90 mm. Hg) reached 83.7% and 80.8% of patients, respectively, target levels of BP and LDL-C <2.5 mmol/l reached 14.5% and 13.1% of patients, respectively, <1.8 mmol/l - 5.8% and 5.1%, respectively. During the observation period no deaths were recorded, other components of MACE were observed in 38 patients (5.8%), including 27 among compliant patients (4.6%) and 11 among non-compliant (15.9%, p<0.01). In 19 out of 38 patients (50%), hospitalization for routine PCI was the end point, ACS - in 12 (31.6%), and stroke - in 7 (18.4%). CONCLUSION: The results of the study demonstrated a sufficient hypolipidemic effect and high safety of Mertenil® and Ekvamer®. A higher adherence to the combined preparation than to two monodrugs was noted. Achieving target levels of BP and LDL-C is problematic, which dictates the expediency of using fixed combinations of drugs, especially in primary prevention.


Assuntos
Anticolesterolemiantes/administração & dosagem , Doenças Cardiovasculares/tratamento farmacológico , Adesão à Medicação/estatística & dados numéricos , Adolescente , Anlodipino , Pressão Sanguínea/efeitos dos fármacos , Colesterol/sangue , LDL-Colesterol/sangue , LDL-Colesterol/efeitos dos fármacos , Combinação de Medicamentos , Humanos , Lipídeos , Lisinopril , Moscou , Resultado do Tratamento
5.
Ter Arkh ; 91(1): 101-107, 2019 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-31090380

RESUMO

In conditions of climate warming with an increase in heat waves associated with an increase in cardiovascular morbidity and mortality, the particular interest is the effect of cardiovascular drugs on adaptation to high temperatures. The review reflects the results of European and domestic studies on the safety of therapy during long and short heat waves. Recommendations for the correction of therapy during this period are given. Self-control of blood pressure (SCAD) is a mandatory component of the therapy of arterial hypertension during heat waves. With the development of clinically significant hypotension, a reduction in the dose of antihypertensive drugs is necessary. It is recommended to start with a dose reduction and/or withdrawal of diuretics and nitrates. Not recommended the complete abolition of antihypertensive therapy because of the risk of hypertensive crises, characteristic of abnormal heat, as well as due to the increase in blood pressure when the weather changes and the temperature drops. With increasing blood pressure during heat waves, it is recommended to give preference to calcium channel antagonists, angiotensin converting enzyme inhibitors (ACE inhibitors) and selective beta-blockers. It is necessary to inform patients about the additional protective effect of statins in order to increase adherence to therapy. Patients taking diuretics require individual daily monitoring of fluid intake and body weight. An overview of recommendations on sanogenic behavior during heat waves is given. Details are considered rules for the use of air conditioning, methods of diagnosis of dehydration and drinking mode Keywords: heat waves, cardiovascular complications, preventive measures.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Anti-Hipertensivos/administração & dosagem , Bloqueadores dos Canais de Cálcio/administração & dosagem , Doenças Cardiovasculares/tratamento farmacológico , Calor Extremo/efeitos adversos , Hipertensão/tratamento farmacológico , Raios Infravermelhos/efeitos adversos , Antagonistas Adrenérgicos beta/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Anti-Hipertensivos/farmacologia , Bloqueadores dos Canais de Cálcio/farmacologia , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/mortalidade , Diuréticos/efeitos adversos , Diuréticos/farmacologia , Humanos , Estações do Ano
6.
Ter Arkh ; 91(1): 108-113, 2019 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-31090381

RESUMO

The review presents current information on the role of NSAIDs in the development of cardiovascular disasters. The development of non-desirable cardiovascular effects and an increase in cardiovascular risk with the administration of NSAIDs, most experts assess in terms of the antagonistic effect on the platelet-vascular homeostasis of metabolites of COX-thromboxane A2 and prostaglandin I2 (prostacyclin). All the presented reviews confirming an increase in the risk of MI complications in the administration of NSAIDs, indicate the class-specificity of this undesirable effect, not homogeneous for different representatives of the group. Important clinical aspects of prescribing NSAIDs for patients with low and moderate cardiovascular risk are the clinical features of the patient and the individual set of risk factors for CVD. Such pharmacokinetic characteristics of NSAIDs as a short half-life, a high degree of binding to blood plasma albumins are indicative of greater safety of NSAIDs, but the final decision must be made based on the accumulated data of clinical trials and meta-analyzes. Keywords: nonsteroidal anti-inflammatory drugs, cardiovascular diseases, cardiovascular risk, lornoxicam, diclofenac sodium, thrombo-elastogram, myocardial infarction, stroke.


Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/efeitos adversos , Doenças Cardiovasculares/tratamento farmacológico , Diclofenaco/administração & dosagem , Diclofenaco/efeitos adversos , Infarto do Miocárdio/tratamento farmacológico , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Humanos , Fatores de Risco
7.
Medicine (Baltimore) ; 98(20): e15484, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31096447

RESUMO

INTRODUCTION: The purpose of this study protocol is to provide the methodology for a review to compare the effect of statins vs physical exercise interventions and the effect of different types of physical exercise, on reducing arterial stiffness associated with cardiovascular diseases and mortality. METHODS AND ANALYSIS: The literature search will be conducted in MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Web of Science databases from their inception until July 31, 2019. We will include randomized controlled trials, nonrandomized experimental studies, and controlled pre-post studies assessing the effect in the general population of statins and physical exercise interventions on arterial stiffness measured by pulse wave velocity. The Cochrane Collaboration's tool and the Quality Assessment Tool for Quantitative Studies will be used to assess the risk of bias for studies included in the systematic review. A Bayesian network meta-analysis will be carried out to determine the comparative effect of the different physical exercise interventions and/or statin intervention. ETHICS AND DISSEMINATION: This study will generate evidence about the effectiveness of both statins and exercise on reducing arterial stiffness that potentially can be transferred to patients and practitioners. Moreover, in light of the importance of reducing arterial stiffness for preventing cardiovascular disease, the evidence provided by this study will be potentially suitable to be included in cardiovascular clinical practice guidelines. STRENGTHS AND LIMITATIONS: This protocol describes the methods of a study examining, using network meta-analysis strategies, the efficacy of statins and different types of exercise on improving arterial stiffness, which is an early marker of atherosclerosis. The results of this study could immediately help clinicians to recommend the best evidence-based intervention to their patients to reduce arterial stiffness and, as a consequence, prevent major complications, such as heart failure, stroke, or myocardial infarction. TRIAL REGISTRATION NUMBER: PROSPERO CRD42019123120.


Assuntos
Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/terapia , Exercício/fisiologia , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Rigidez Vascular/efeitos dos fármacos , Doenças Cardiovasculares/tratamento farmacológico , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Meta-Análise em Rede , Ensaios Clínicos Controlados não Aleatórios como Assunto , Avaliação de Resultados (Cuidados de Saúde) , Análise de Onda de Pulso/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Rigidez Vascular/fisiologia
8.
Nat Commun ; 10(1): 1981, 2019 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-31040273

RESUMO

Cardiovascular and metabolic disease (CMD) remains a main cause of premature death worldwide. Berberine (BBR), a lipid-lowering botanic compound with diversified potency against metabolic disorders, is a promising candidate for ameliorating CMD. The liver is the target of BBR so that liver-site accumulation could be important for fulfilling its therapeutic effect. In this study a rational designed micelle (CTA-Mic) consisting of α-tocopheryl hydrophobic core and on-site detachable polyethylene glycol-thiol shell is developed for effective liver deposition of BBR. The bio-distribution analysis proves that the accumulation of BBR in liver is increased by 248.8% assisted by micelles. Up-regulation of a range of energy-related genes is detectable in the HepG2 cells and in vivo. In the high fat diet-fed mice, BBR-CTA-Mic intervention remarkably improves metabolic profiles and reduces the formation of aortic arch plaque. Our results provide proof-of-concept for a liver-targeting strategy to ameliorate CMD using natural medicines facilitated by Nano-technology.


Assuntos
Berberina/farmacologia , Hipoglicemiantes/uso terapêutico , Nanotecnologia/métodos , Animais , Células CACO-2 , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/tratamento farmacológico , Dislipidemias/sangue , Dislipidemias/tratamento farmacológico , Células Hep G2 , Humanos , Hipoglicemiantes/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Espectroscopia de Ressonância Magnética , Masculino , Doenças Metabólicas/sangue , Doenças Metabólicas/tratamento farmacológico , Camundongos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
9.
Drugs Today (Barc) ; 55(5): 329-344, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31131843

RESUMO

Atherosclerotic cardiovascular disease is the leading cause of death all over the world. Its etiopathogenesis involves many correlated processes, with hypercholesterolemia being one of the main risk factors. Several large clinical trials have established the association between low-density lipoprotein cholesterol (LDL-C) levels and cardiovascular events. With the aim to take control over high LDL-C levels, several drugs with different targets in the cholesterol pathway have been developed. Statins are the cornerstone of pharmacological lipid-lowering treatment, although they are not always successful in attaining the recommended LDL-C levels. Therefore, newer and more potent therapies have been developed, being prominent among them ezetimibe and especially the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. Recent trials with these new therapies have reaffirmed the theory of 'the lower, the better' when it comes to LDL-C levels, and 'the earlier, the better' when it comes to atherosclerotic physiopathology.


Assuntos
Anticolesterolemiantes/uso terapêutico , Aterosclerose/tratamento farmacológico , Doenças Cardiovasculares/tratamento farmacológico , LDL-Colesterol/antagonistas & inibidores , Pró-Proteína Convertase 9/antagonistas & inibidores , Subtilisinas/antagonistas & inibidores , Aterosclerose/prevenção & controle , Doenças Cardiovasculares/prevenção & controle , Humanos
10.
Oxid Med Cell Longev ; 2019: 2867516, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31049131

RESUMO

Reactive Oxygen Species (ROS) play an essential dual role in living systems. Healthy levels of ROS modulate several signaling pathways, but at the same time, when they exceed normal physiological amounts, they work in the opposite direction, playing pivotal functions in the pathophysiology of multiple severe medical conditions (i.e., cancer, diabetes, neurodegenerative and cardiovascular diseases, and aging). Therefore, the research for methods to detect their levels via light-sensitive fluorescent probes has been extensively studied over the years. However, this is not the only link between light and ROS. In fact, the modulation of ROS mediated by light has been exploited already for a long time. In this review, we report the state of the art, as well as recent developments, in the field of photostimulation of oxidative stress, from photobiomodulation (PBM) mediated by naturally expressed light-sensitive proteins to the most recent optogenetic approaches, and finally, we describe the main methods of exogenous stimulation, in particular highlighting the new insights based on optically driven ROS modulation mediated by polymeric materials.


Assuntos
Antioxidantes/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , Diabetes Mellitus/tratamento farmacológico , Doenças Neurodegenerativas/tratamento farmacológico , Espécies Reativas de Oxigênio/antagonistas & inibidores , Envelhecimento/efeitos dos fármacos , Envelhecimento/metabolismo , Envelhecimento/patologia , Animais , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/patologia , Diabetes Mellitus/metabolismo , Diabetes Mellitus/patologia , Humanos , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/patologia , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos
11.
Int J Mol Sci ; 20(9)2019 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-31035359

RESUMO

Cardiovascular diseases (CVDs) still represent the greatest burden on healthcare systems worldwide. Despite the enormous efforts over the last twenty years to limit the spread of cardiovascular risk factors, their prevalence is growing and control is still suboptimal. Therefore, the availability of new therapeutic tools that may interfere with different pathophysiological pathways to slow the establishment of clinical CVDs is important. Previously, the inhibition of neurohormonal systems, namely the renin-angiotensin-aldosterone system (RAAS) and the sympathetic nervous system, has proven to be useful in the treatment of many CVDs. Attempts have recently been made to target an additional hormonal system, that of the natriuretic peptides (NPs), which, when dysregulated, can also play a role in the development CVDs. Indeed, a new class of drug, the angiotensin receptor-neprilysin inhibitors (ARNi), has the ability to counteract the effects of angiotensin II as well as to increase the activity of NPs. ARNi have already been proven to be effective in the treatment of heart failure with reduced ejection fraction. New evidence has suggested that, in the next years, the field of ARNi application will widen to include other CVDs, such as heart failure, with preserved ejection fraction and hypertension.


Assuntos
Antagonistas de Receptores de Angiotensina/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , Sistema Renina-Angiotensina/efeitos dos fármacos , Animais , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Hipertensão/tratamento farmacológico , Neprilisina/antagonistas & inibidores
12.
Int J Nanomedicine ; 14: 2809-2828, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31114196

RESUMO

Omega-3 polyunsaturated fatty acids (ω-3 PUFAs) are dietary factors involved in the prevention of cardiovascular, inflammatory, and neoplastic diseases. A multidisciplinary approach - based on recent findings in nutritional science, lipid biochemistry, biotechnology, and biology of inflammation and cancer - has been recently employed to develop ω-3 PUFA-containing nanoformulations with an aim to protect these fatty acids from degradation, increase their bioavailability and delivery to target tissues, and, thus, enhance their bioactivity. In some cases, these nanoformulations were designed to administer ω-3 PUFAs in combination with other nutraceuticals or conventional/innovative drugs. The aim of this strategy was to increase the activities of the compounds contained in the nanoformulation and to reduce the adverse effects often induced by drugs. We herein analyze the results of papers evaluating the potential use of ω-3 PUFA-containing nanomaterials in fighting cardiovascular diseases and cancer. Future directions in this field of research are also provided.


Assuntos
Doenças Cardiovasculares/tratamento farmacológico , Composição de Medicamentos , Ácidos Graxos Ômega-3/uso terapêutico , Nanomedicina , Neoplasias/tratamento farmacológico , Doenças Cardiovasculares/prevenção & controle , Humanos , Neoplasias/prevenção & controle , Resultado do Tratamento
13.
Life Sci ; 229: 67-79, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31085245

RESUMO

Endothelial dysfunction and vascular reactivity defects secondary to metabolic and immunological disorders carry risk of serious cardiovascular complications. Here, the effects of the phosphodiesterase (PDE) inhibitors vardenafil and cilostazol were examined against rheumatoid arthritis (RA)/diabetes mellitus (DM)-co-morbidity-induced endothelial dysfunction and vascular reactivity defects. After setting of RA/DM-co-morbidity model, rats were divided into a normal control group, an RA/DM-co-morbidity group, and two treatment groups receiving oral vardenafil (10 mg/kg/day) and cilostazol (30 mg/kg/day) for 21 days after RA/DM-co-morbidity induction. Aorta was isolated for biochemical estimations of the pro-inflammatory vasoconstrictor molecules angiotensin-II (Ang-II) and endothelin-1 (ET-1), the adhesion molecules P-selectin and vascular cell adhesion molecule-1 (VCAM-1), the energy sensor adenosine-5'-monophosphate-activated protein kinase (AMPK), and the vasodilator anti-inflammatory molecule vasoactive intestinal peptide (VIP) using enzyme-linked immunosorbent assay (ELISA) and western blot analysis. Immunohistochemical estimations of endothelial nitric oxide synthase (eNOS) and matrix metalloproteinase (MMP)-2 were performed coupled with histopathological examination using routine hematoxylin and eosin (H&E) and special Masson trichrome staining. The in vitro study was conducted using aortic strips where cumulative concentration response curves were done for the endothelium-dependent relaxing factor acetylcholine and the endothelium-independent relaxing factor sodium nitroprusside after submaximal contraction with phenylephrine. Vardenafil and cilostazol significantly improved endothelial integrity biomarkers in vivo supported with histopathological findings in addition to improved vasorelaxation in vitro. Apart from their known PDE inhibition, up-regulation of vascular AMPK and eNOS coupled with down-regulation of Ang-II, ET-1, P-selectin, VCAM-1 and MMP-2 may explain vardenafil and cilostazol protective effect against RA/DM-co-morbidity-induced endothelial dysfunction and vascular reactivity defects.


Assuntos
Artrite Experimental/complicações , Artrite Reumatoide/complicações , Doenças Cardiovasculares/tratamento farmacológico , Cilostazol/farmacologia , Diabetes Mellitus Experimental/complicações , Endotélio Vascular/efeitos dos fármacos , Dicloridrato de Vardenafila/farmacologia , Vasodilatadores/farmacologia , Animais , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/metabolismo , Comorbidade , Endotélio Vascular/metabolismo , Endotélio Vascular/patologia , Feminino , Ratos
14.
Medicine (Baltimore) ; 98(18): e15188, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31045761

RESUMO

While it is important to treat lifestyle-related diseases for the primary and secondary prevention of cardiovascular diseases, medication adherence is still poor. Although various causes of poor adherence have been reported, the differences between physicians and their patients regarding the recognition of medication adherence have not been well-investigated.We administered a questionnaire about medication adherence to 300 outpatients and their 23 cardiologists at the Department of Cardiology, Fukuoka University Hospital. The questionnaires for patients and physicians included acceptable total number of drug doses and dosing schedule, forgetting to take the medicine, and dose-reduction or -increase based on self-judgement. The patients were 70.6 ±â€Š12.3 years old and 61.0% (n = 183) were male. Patients reported that it was acceptable to receive 0-5 doses twice daily. The patients were divided into two groups: an agreement group, in which physicians and their patients had the same answer to the question regarding forgetting medication (203 cases; 67.7%), and a disagreement group (97 cases; 32.3%). Overall, the inter-rater agreement between physicians and patients with regard to forgetting medication was significant, but slight (κ coefficient = 0.12). In a multivariate analysis, absence of hypertension [odds ratio (OR): 0.21, 95% confidence interval (CI): 0.09-0.50, P < .001), ß-blocker usage (OR: 1.86, 95% CI: 1.11-3.12, P = .02), and biguanide usage (OR: 4.04, 95% CI: 1.43-11.41, P = .01) were independent predictors of disagreement with regard to forgetting medication.The inter-rater agreement between physicians and patients with regard to medication adherence was slight. An increase in inter-rater agreement should improve medication adherence.


Assuntos
Doenças Cardiovasculares/tratamento farmacológico , Hipertensão/tratamento farmacológico , Adesão à Medicação/estatística & dados numéricos , Relações Médico-Paciente/ética , Idoso , Idoso de 80 Anos ou mais , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Doenças Cardiovasculares/psicologia , Feminino , Humanos , Hipertensão/psicologia , Japão/epidemiologia , Estilo de Vida , Masculino , Adesão à Medicação/psicologia , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Prevenção Secundária , Autorrelato/estatística & dados numéricos , Inquéritos e Questionários
15.
Autoimmun Rev ; 18(7): 679-690, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31059840

RESUMO

Patients with rheumatoid arthritis (RA) suffer cardiovascular events 1.5-2 fold than the general population, and cardiovascular (CV) events are leading cause of death in patients with RA. It is known that patients with RA have endothelial dysfunction, related with impaired function of endothelial progenitor cells (EPCs). The mechanistic pathways leading to endothelial function are complicated, but understanding these mechanisms may open new frontiers of management and therapies to patients suffering from atherosclerosis. Inflammation is a key factor in atherosclerosis, including endothelial function, plaque stabilization and post infarct remodeling; thus, inhibition of TNF-α may affect the inflammatory burden and plaque vulnerability leading to less cardiovascular events and myocardial infarctions. An aggressive management of inflammation may lead to a significant improvement in the clinical cardiovascular outcome of patients with RA. The clinical evidence that showed a reduced risk of CV events following treatment with anti-inflammatory agents may suggest a new approach to treat atherosclerosis, i.e., inhibition of inflammation using biological medications that were primarily aimed to treat the high scale inflammation of RA and other autoimmune-inflammatory diseases, but may be useful also to prevent progression of atherosclerosis.


Assuntos
Anti-Inflamatórios/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Doenças Cardiovasculares/tratamento farmacológico , Animais , Artrite Reumatoide/complicações , Artrite Reumatoide/epidemiologia , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Humanos
16.
Ann Hematol ; 98(8): 1891-1904, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31079264

RESUMO

Imatinib, the first BCR/ABL kinase inhibitor approved for the treatment of chronic myeloid leukemia (CML), has changed the long-term outcome of patients affected by this disease. The aim of our analysis was to report, after a median follow-up of 10.2 years (range 5.8-14.8), the long-term outcome, efficacy, and safety of imatinib treatment (frontline and after interferon failure) in a single institution cohort of 459 patients with CML in chronic phase treated outside of clinical trials. The 10-year overall survival of the whole cohort was 77.1%, while the 10-year probability of dying due to CML and other causes was 7.8% and 16%, respectively. The prognostic value of the BCR-ABL1 ratio at 3 months (⩽ 10%) and of complete cytogenetic response and major molecular response at 1 year was confirmed also in the real-life practice. The EUTOS long-term survival score better stratified the baseline risk of dying of CML compared with other risk scores. Two hundred thirty-six (51.4%) patients achieved a deep molecular response during imatinib treatment after a median time of 4.57 years, and 95 (20.6%) had a stable deep molecular response maintained for at least 2 consecutive years. Imatinib was associated with a low rate of serious cardiovascular events and second neoplasia. This 10-year real-life follow-up study shows that imatinib maintains efficacy over time and that long-term administration of imatinib is not associated with notable cumulative or late toxic effects.


Assuntos
Antineoplásicos/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , Mesilato de Imatinib/uso terapêutico , Leucemia Mieloide de Fase Crônica/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Adulto , Idoso , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/mortalidade , Progressão da Doença , Feminino , Seguimentos , Humanos , Interferons/administração & dosagem , Leucemia Mieloide de Fase Crônica/complicações , Leucemia Mieloide de Fase Crônica/diagnóstico , Leucemia Mieloide de Fase Crônica/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Indução de Remissão , Análise de Sobrevida , Resultado do Tratamento
17.
Nat Commun ; 10(1): 1891, 2019 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-31015401

RESUMO

Genome-wide association studies (GWASs) of medication use may contribute to understanding of disease etiology, could generate new leads relevant for drug discovery and can be used to quantify future risk of medication taking. Here, we conduct GWASs of self-reported medication use from 23 medication categories in approximately 320,000 individuals from the UK Biobank. A total of 505 independent genetic loci that meet stringent criteria (P < 10-8/23) for statistical significance are identified. We investigate the implications of these GWAS findings in relation to biological mechanism, potential drug target identification and genetic risk stratification of disease. Amongst the medication-associated genes are 16 known therapeutic-effect target genes for medications from 9 categories. Two of the medication classes studied are for disorders that have not previously been subject to large GWAS (hypothyroidism and gastro-oesophageal reflux disease).


Assuntos
Uso de Medicamentos/estatística & dados numéricos , Genoma Humano , Estudo de Associação Genômica Ampla , Testes Farmacogenômicos/estatística & dados numéricos , Medicamentos sob Prescrição/uso terapêutico , Idoso , Bancos de Espécimes Biológicos , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/fisiopatologia , Bases de Dados Factuais , Feminino , Gastroenteropatias/tratamento farmacológico , Gastroenteropatias/genética , Gastroenteropatias/fisiopatologia , Loci Gênicos , Humanos , Masculino , Transtornos Mentais/tratamento farmacológico , Transtornos Mentais/genética , Transtornos Mentais/fisiopatologia , Pessoa de Meia-Idade , Doenças Musculoesqueléticas/tratamento farmacológico , Doenças Musculoesqueléticas/genética , Doenças Musculoesqueléticas/fisiopatologia , Autoadministração , Autorrelato , Reino Unido
18.
Int J Mol Sci ; 20(7)2019 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-30934670

RESUMO

Resveratrol, the phenolic substance isolated initially from Veratrum grandiflorum and richly present in grapes, wine, peanuts, soy, and berries, has been attracting attention of scientists and medical doctors for many decades. Herein, we review its effects on the vascular system. Studies utilizing cell cultures and pre-clinical models showed that resveratrol alleviates oxidative stress and inflammation. Furthermore, resveratrol suppresses vascular smooth muscle cell proliferation, promotes autophagy, and has been investigated in the context of vascular senescence. Pre-clinical models unambiguously demonstrated numerous vasculoprotective effects of resveratrol. In clinical trials, resveratrol moderately diminished systolic blood pressure in hypertensive patients, as well as blood glucose in patients with diabetes mellitus. Yet, open questions remain, as exemplified by a recent report which states that the intake of resveratrol might blunt certain positive effects of exercise in older persons, and further research addressing the framework for long-term use of resveratrol as a food supplement, will stay in demand.


Assuntos
Sistema Cardiovascular/efeitos dos fármacos , Resveratrol/farmacologia , Animais , Cardiotônicos/farmacologia , Cardiotônicos/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/patologia , Ensaios Clínicos como Assunto , Modelos Animais de Doenças , Humanos , Resveratrol/uso terapêutico
19.
Nihon Yakurigaku Zasshi ; 153(4): 172-178, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-30971657

RESUMO

Apelin is an endogenous peptide ligand for APJ receptor, which is widely expressed in human body, and exerts various physiological effects such as vasodilation, inotropic effect, water balance, heart development, angiogenesis and energy metabolism. The beneficial effects of Apelin in cardiovascular diseases have been elucidated, and the roles of Apelin in aging-associated diseases are recently implicated. The mechanisms for therapeutic effects of Aplein include an antagonistic action to renin-angiotensin system (RAS) in addition to inotropic and vasodilatory actions. We have revealed that endogenous Apelin negatively regulates RAS via upregulation of Angiotensin converting enzyme 2 (ACE2). In addition, a second ligand for APJ receptor, Elabela/Toddler, was identified as an essential hormone for heart development, and it has been reported to have physiological effects similar to Apelin. We and others have shown that Elabela exerts inotropic and protective effects in the heart. Although the number of heart failure patients is rapidly increasing, the pathophysiology of heart failure remains elusive and further development of new therapeutic option is awaited. Apelin is a unique bifunctional molecule, which has both inotropic and cardioprotective effects in heart failure, and thus further elucidation of the mechanisms for Apelin/Elabela-APJ signaling would contribute to development of a novel therapeutics for heart failure patients.


Assuntos
Apelina/uso terapêutico , Doenças Cardiovasculares , Receptores de Apelina , Doenças Cardiovasculares/tratamento farmacológico , Pré-Escolar , Humanos , Peptídeos e Proteínas de Sinalização Intercelular , Receptores Acoplados a Proteínas-G
20.
Cardiovasc Diabetol ; 18(1): 54, 2019 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-31029144

RESUMO

With an increasing global burden of coronary artery disease (CAD), early detection and timely management of risk factors are crucial to reduce morbidity and mortality in such patients. Diabetes mellitus (DM) is considered an independent risk factor for the development of CAD. Metformin, an anti-diabetic drug, has been shown in pre-clinical and clinical studies, to lower the cardiovascular events in the DM patients. Growing evidence suggests that metformin has a protective effect on coronary artery beyond its hypoglycemic effects. Given its global availability, route of administration and cost, metformin provides an alternate/additional therapeutic option for primary and secondary prevention of CAD in DM and non-diabetics alike. Future prospective cohort-based studies and randomized clinical trials are needed to identify 'at-risk' population who may potentially benefit from metformin.


Assuntos
Glicemia/efeitos dos fármacos , Fármacos Cardiovasculares/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , Diabetes Mellitus/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Animais , Biomarcadores/sangue , Glicemia/metabolismo , Fármacos Cardiovasculares/efeitos adversos , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/fisiopatologia , Tomada de Decisão Clínica , Diabetes Mellitus/sangue , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiologia , Humanos , Hipoglicemiantes/efeitos adversos , Metformina/efeitos adversos , Fatores de Risco , Resultado do Tratamento
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