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2.
J Hypertens ; 41(7): 1108-1116, 2023 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-37016911

RESUMO

BACKGROUND: The magnitude of blood pressure (BP)-lowering effects and decrease of the adverse effects of thiazide diuretics provided by potassium-sparing diuretics remain uncertain. The aim of this study was to compare the BP-lowering efficacy and the incidence of adverse effects of high (T+) and low-dose (T-) thiazide diuretics, alone or combined with high (PS+) or low-dose (PS-) potassium-sparing diuretics in patients with primary hypertension. METHODS: A systematic literature search was performed in PubMed/MEDLINE, the Cochrane Central Register of Controlled Trials, Embase, Web of Science, Scopus and LILACS. Randomized double-blind placebo or active-controlled trials (RCT) with 3 weeks to 1 year of follow-up were included. Sample size, mean and standard deviation from baseline, follow-up and change from baseline values were extracted by two independent reviewers. Pairwise random effect models and Bayesian network meta-analysis models were used to compare the effects of treatments. The risk of bias in individual studies was assessed using the Rob 1.0 tool. The primary outcome was the mean difference in office SBP. Secondary outcomes were the mean difference in biochemical parameters and the incidence of nonmelanoma skin cancer. RESULTS: Two hundred and seventy-six double-blind RCTs involving 58 807 participants (mean age: 55 years; 45% women) were included. All treatment groups were more effective than placebo in lowering BP, with mean differences (MDs) of change from baseline ranging from -7.66 mmHg [95% credible interval (95% CrI), -8.53 to -6.79] for T- to -12.77 mmHg (95% CrI, -15.22 to -10.31) for T+PS-. T+ alone or combined with potassium-sparing was more effective in reducing BP than T-. The surface under the cumulative ranking curve (SUCRA) estimated ranking showed that the best effectiveness in lowering SBP was found for T+PS- (0.69), T+PS+ (0.65) and T+ (0.54). Compared with placebo, all treatments (except T-PS-) were associated with more potassium reduction and T+ compared with all other treatments and T- when compared with T-PS-. Compared with placebo, all active treatments (except T+PS+) showed higher elevations of uric acid. The increase of plasma glucose promoted by thiazides alone was reduced by potassium-sparing agents. CONCLUSION: Thiazides with potassium-sparing diuretics are associated with increased BP-lowering efficacy compared with thiazides alone while minimizing hypokalaemia and hyperglycaemia. These findings demonstrate that thiazide and potassium-sparing diuretic combination is preferable to thiazide alone in treating hypertension.


Assuntos
Hipertensão , Inibidores de Simportadores de Cloreto de Sódio , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Inibidores de Simportadores de Cloreto de Sódio/uso terapêutico , Inibidores de Simportadores de Cloreto de Sódio/farmacologia , Anti-Hipertensivos/uso terapêutico , Metanálise em Rede , Teorema de Bayes , Ensaios Clínicos Controlados Aleatórios como Assunto , Hipertensão/tratamento farmacológico , Hipertensão/induzido quimicamente , Pressão Sanguínea , Diurético Poupador de Potássio/uso terapêutico , Tiazidas/uso terapêutico , Potássio/farmacologia , Diuréticos/uso terapêutico
3.
Nephrol Dial Transplant ; 38(10): 2389-2406, 2023 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-37118876

RESUMO

BACKGROUND: Evidence comparing different exercise modalities in individuals undergoing hemodialysis remains incipient. Our aim was to conduct a systematic review and network meta-analysis of randomized clinical trials to compare and synthesize the efficacy of five different intradialytic exercise modalities and home-based training in this population. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: Studies were searched in PubMed/MEDLINE, Cochrane Library, Embase, Cinahl, and Scopus from their inception to 19 September 2022. We used traditional random-effects models and Bayesian network meta-analysis models. The risk of bias was assessed using the RoB v.2.0 tool, and the assessment of confidence in the results through the Confidence in Network Meta-Analysis (CINeMA) tool. RESULTS: Seventy-eight studies involving 3326 participants were included. Our network meta-analysis showed that combined training was the intervention with the best performance to increase VO2 peak [mean difference (MD) = 3.94 ml/kg/min; 95% credible interval (CrI), 2.38 to 5.76] and to reduce diastolic blood pressure (MD = -5.19 mmHg; 95%CrI, -9.35 to -0.96) compared to the usual care group. Inspiratory muscle training was the intervention that most improved the 6-minute walk test distance (MD = 70.97 m; 95%CrI, 18.09 to 129.87). C-reactive protein decreased in resistance training (MD = -2.6 mg/l; 95%CrI, -4.97 to -0.33) and aerobic training (MD = -1.4 mg/l; 95%CrI, -3.15 to -0.06). Kt/V improved in aerobic training (MD = 0.11; 95%CrI, 0.02 to 0.18), and SF-36 physical functioning outcomes improved in resistance training (MD = 10.66 points; 95%Crl, 1.91 to 20.22). No intradialytic exercise modality was superior to others or comparable with home-based training in improving the evaluated outcomes. Subgroup analysis revealed that exercise interventions >12 weeks improved functional capacity more than interventions ≤12 weeks, and that combined training reduces diastolic blood pressure only after 12 weeks of follow-up. Furthermore, our results suggest that moderate or moderate-to-vigorous intensity training leads to more pronounced improvements in functional capacity, whereas mild or mild-to-moderate intensity training does not have the same effect. In this review, most of the included studies were assessed as having some concern, which resulted in a low to very low level of confidence in the overall findings. CONCLUSIONS: Both intradialytic training and home-based training can promote benefits for individuals undergoing hemodialysis, with no evidence of the superiority of either training modality over the other.


Assuntos
Terapia por Exercício , Diálise Renal , Humanos , Metanálise em Rede , Teorema de Bayes , Ensaios Clínicos Controlados Aleatórios como Assunto , Terapia por Exercício/métodos , Diálise Renal/efeitos adversos , Qualidade de Vida
6.
Biol Res Nurs ; 24(4): 519-529, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35506158

RESUMO

BACKGROUND: The prevalence of obesity among children as well as the beneficial effects of physical exercise (PE) on weight loss has been determined by modulating the secretory factors of adipose tissue. PE has also been shown to have beneficial effects on obesity. OBJECTIVE: The objective of this systematic review and meta-analysis was to investigate the effects of physical exercise (PE) on adiponectin and other important health markers in children. DATA SOURCES: We searched 6 electronic databases (PubMed/Medline, Embase, Cochrane Library, Cinahl, Scopus, and Web of Science) and Google Scholar for randomized controlled trials from inception to December 15, 2021. We used random-effects models to estimate weighted mean difference (WMD) with 95% confidence intervals (CI). STUDY SELECTION: Fourteen studies were included (N = 468 participants; mean age: 14 years). RESULTS: In general, PE increased adiponectin (WMD: 0.91 µg/mL; 95% CI, 0.27 to 1.55, p = 0.005), high-density lipoprotein cholesterol (HDL-C) (WMD: 1.01 mg/dL; 95% CI, 0.33 to 1.69, p = 0.004), and VO2max (WMD: 2.52 mL.kg.min; 95% CI, 1.41 to 3.62, p = 0.00,001). The levels of c-reactive protein (WMD: -0.37 mg/L; 95% CI, -0.57 to -0.17, p = 0.0003), insulin (WMD: -4.61 µIU/ml; 95% CI, -5.46 to -3.76, p = 0.00,001), fasting glucose (WMD: -5.11 mg/dL; 95% CI, -7.88 to -2.34, p = 0.0003), and insulin resistance index (WMD: -1.44; 95% CI, -1.92 to -0.96, p = 0.00,001), decreased significantly. CONCLUSION: Our study showed that PE may increase the level of adiponectin, HDL-C, and VO2max in children.


Assuntos
Adiponectina , Doenças Cardiovasculares , Adolescente , Biomarcadores , Criança , Exercício Físico , Humanos , Obesidade , Ensaios Clínicos Controlados Aleatórios como Assunto
8.
Syst Rev ; 11(1): 23, 2022 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-35135630

RESUMO

BACKGROUND: The use of thiazide (T) diuretics for the treatment of hypertension may be associated with adverse metabolic effects, which can be minimized by combining thiazides with potassium-sparing (PS) diuretics. The additional blood pressure (BP)-lowering effect provided by the addition of a PS diuretic is unclear. Due to a large number of drugs in the T diuretics class, and the possible difference between them, there is a need to identify the best available evidence for health decision-making. This systematic review with network meta-analysis aims to compare the antihypertensive efficacy of T diuretics alone or in combination with a PS diuretic in patients with primary hypertension, as well as the safety of such drugs through the measurement of drug-related adverse events. METHODS: A comprehensive electronic search will be conducted in six electronic bibliographic databases (PubMed/MEDLINE, Cochrane Library, Embase, Web of Science, Scopus, Lilacs), a registration database ( ClinicalTrials.gov ), and Educational Resources Information Center (ERIC [ProQuest]), published from inception to the date of the search. The search will be updated towards the end of the review. A hand search of the reference sections of the included studies and cited studies will also be performed. In case of missing data, authors will be contacted by e-mail or academic social networking sites whenever possible. To be included in the review, studies must be double-blind randomized controlled trials evaluating T diuretics alone or in combination with PS diuretics in patients with primary hypertension. The primary outcome measure will be office BP. Ambulatory BP monitoring (ABPM), non-melanoma skin cancer, major adverse cardiovascular events, laboratory parameters, and the number of withdrawals will be included as secondary outcomes. The results will be quantitatively summarized using differences between the mean change from baseline or differences between means for quantitative outcomes and relative risk for dichotomous outcomes. Results will be presented as mean or relative risk with credible intervals through a league table. The treatments will also be ranked using the surface under the cumulative ranking curve method. The risk of bias will be assessed through the RoB 1.0 tool. DISCUSSION: To the best of our knowledge, this review will be the first to synthesize currently available evidence on the antihypertensive efficacy of different T diuretics alone or in combination with PS diuretics in adults with hypertension. The goals of hypertension treatment are to control high BP and to reduce associated cardiovascular morbidity and mortality, using the most appropriate therapy. Thiazides are widely used for pharmacological treatment due to their demonstrated effectiveness in reducing BP, favorable safety profile, and low cost. The results of this study will provide evidence regarding the best therapeutic strategies with T and PS diuretics, evidencing interventions with better antihypertensive efficacy and safety profile. TRIAL REGISTRATION: This systematic review and network meta-analysis was prospectively registered at the PROSPERO database ( CRD42018118492 ).


Assuntos
Hipertensão , Inibidores de Simportadores de Cloreto de Sódio , Adulto , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea , Diuréticos/uso terapêutico , Humanos , Hipertensão/tratamento farmacológico , Metanálise como Assunto , Metanálise em Rede , Potássio/farmacologia , Potássio/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Inibidores de Simportadores de Cloreto de Sódio/efeitos adversos , Inibidores de Simportadores de Cloreto de Sódio/uso terapêutico , Revisões Sistemáticas como Assunto
11.
Expert Opin Pharmacother ; 22(4): 483-495, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33016816

RESUMO

INTRODUCTION: Familial hypercholesterolemia (FH) is a frequent genetic disorder characterized by elevated LDL-cholesterol (LDL-C) and early onset of atherosclerosis. AREAS COVERED: The authors provide an overview of the pediatric FH scenario, with emphasis on the role of statins as the preferred pharmacological therapy, discussing their potential benefits, as well as adverse effects, and the remaining uncertainties about their use in this population. They also comment on other lipid-lowering therapies. EXPERT OPINION: Statin therapy is recommended after the ages of 8-10 years old for heterozygous FH patients and can reduce LDL-C by 24-50% depending on drug type and dosage. For more severe cases, higher doses and adjuvant therapies like ezetimibe may be necessary and treatment should be started at diagnosis, as is the case of homozygous FH. Statins reduce progression of subclinical vascular disease and may reduce early cardiovascular events. The available evidence indicates safety of statins in children with no apparent harms related to growth, sexual maturation, steroid hormones, glucose levels, cognitive function, or muscle and liver problems, in comparison with placebo. Newer treatments like lomitapide, PCSK9 inhibitors, bempedoic acid and evinacumab need to be adequately evaluated in pediatric FH patients with more severe dyslipidemia.


Assuntos
Anticolesterolemiantes/uso terapêutico , Hiperlipoproteinemia Tipo II/tratamento farmacológico , Aterosclerose/prevenção & controle , Criança , LDL-Colesterol/sangue , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Inibidores de PCSK9
12.
Clinics ; 76: e2518, 2021. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1153969

RESUMO

The novel coronavirus disease (COVID-19) showed increased morbidity and mortality rates and worse prognosis in individuals with underlying chronic diseases, especially cardiovascular disease and its risk factors, such as hypertension, diabetes, and obesity. There is also evidence of possible links among COVID-19, myocardial infarction, and stroke. Emerging evidence suggests a pro-inflammatory milieu and hypercoagulable state in patients with this infection. Despite anticoagulation, a large proportion of patients requiring intensive care may develop life-threatening thrombotic complications. Indeed, the levels of some markers of hemostatic activation, such as D-dimer, are commonly elevated in COVID-19, indicating potential risk of deep vein thrombosis and pulmonary thromboembolism. In this review, we critically examine and discuss aspects of hypercoagulability and inflammation in COVID-19 and the possible benefits of statins in this scenario, with emphasis on their underlying molecular mechanisms. Moreover, we present recommendations on the use of antiviral drugs in combination with statins.


Assuntos
Humanos , Trombose , Infecções por Coronavirus , Coronavirus , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Betacoronavirus , Inflamação/tratamento farmacológico , Anticoagulantes/efeitos adversos
13.
Clinics ; 76: e2342, 2021. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1286087

RESUMO

Among the multiple uncertainties surrounding the novel coronavirus disease (COVID-19) pandemic, a research letter published in The Lancet implicated drugs that antagonize the renin-angiotensin-aldosterone system (RAAS) in an unfavorable prognosis of COVID-19. This report prompted investigations to identify mechanisms by which blocking angiotensin-converting enzyme 2 (ACE2) could lead to serious consequences in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The possible association between RAAS inhibitors use and unfavorable prognosis in this disease may have been biased by the presence of underlying cardiovascular diseases. As the number of COVID-19 cases has increased worldwide, it has now become possible to investigate the association between RAAS inhibitors and unfavorable prognosis in larger cohorts. Observational studies and one randomized clinical trial failed to identify any consistent association between the use of these drugs and unfavorable prognosis in COVID-19. In view of the accumulated clinical evidence, several scientific societies recommend that treatment with RAAS inhibitors should not be discontinued in patients diagnosed with COVID-19 (unless contraindicated). This recommendation should be followed by clinicians and patients.


Assuntos
Humanos , Coronavirus , COVID-19 , Sistema Renina-Angiotensina , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Peptidil Dipeptidase A/metabolismo , Antagonistas de Receptores de Angiotensina/efeitos adversos , SARS-CoV-2
14.
Arq. bras. cardiol ; 115(4): 690-700, out. 2020. tab, graf
Artigo em Português | SES-SP, LILACS | ID: biblio-1131334

RESUMO

Resumo A farmacogenômica (FGx) investiga a interação entre genes e medicamentos. Através da análise de regiões específicas do DNA, informações sobre o perfil de metabolização do paciente para um determinado fármaco podem ser descritas, assim como o perfil esperado de resposta ao tratamento. Objetivamente, esse tipo de teste pode ter impacto no tratamento de pacientes que não estão respondendo adequadamente a um determinado medicamento, seja pela ausência dos efeitos esperados ou em virtude do aparecimento de efeitos adversos. Neste cenário, o objetivo desta revisão é o de informar o cardiologista clínico sobre esta importante área do conhecimento e atualizá-lo sobre o tema, procurando preencher as lacunas no que diz respeito à relação custo-benefício da aplicação da FGx nas doenças cardiovasculares, além de fornecer informações para a implementação da terapia guiada pela FGx na prática clínica.


Assuntos
Humanos , Farmacogenética , Doenças Cardiovasculares/genética
15.
Arq. bras. cardiol ; 114(5): 823-826, maio 2020.
Artigo em Português | SES-SP, LILACS | ID: biblio-1131221

RESUMO

Resumo Em dezembro de 2019, um novo coronavírus humano, chamado síndrome respiratória aguda grave do coronavírus 2 (SARS-CoV-2) ou nomeado doença de coronavírus (COVID-19) pela Organização Mundial da Saúde, surgiu na cidade de Wuhan, China. Difundido globalmente, é atualmente considerado pandêmico, com aproximadamente 3 milhões de casos no mundo no final de abril. Seus sintomas incluem febre, tosse, dor de cabeça e falta de ar, esse último considerado o sintoma principal. Por sua vez, acredita-se que haja uma relação entre o COVID-19 e danos ao músculo cardíaco, e pacientes com hipertensão e diabetes, por exemplo, parecem apresentar prognóstico pior. Portanto, o COVID-19 pode piorar em indivíduos com condições adversas subjacentes. Um número não negligenciável de pacientes internados com este vírus tinham doenças cardiovasculares ou cerebrovasculares. A resposta inflamatória sistêmica e distúrbios do sistema imunológico durante a progressão da doença podem estar por trás dessa associação. Além disso, o vírus usa os receptores da enzima conversora da angiotensina (ECA), mais especificamente da ECA2, para penetrar nas células; portanto, o uso de fármacos inibidores de ECA e bloqueadores de receptores de angiotensina pode causar um aumento nestes receptores, assim facilitando a entrada do vírus na célula. No entanto, não há evidências científicas que apóiem a interrupção desses medicamentos. Considerando que são fundamentais para o manejo de certas doenças crônicas, os riscos e benefícios da sua retirada devem ser cuidadosamente ponderados neste cenário. Finalmente, cardiologistas e profissionais de saúde devem estar cientes dos riscos de infecção e se proteger o máximo possível, dormindo adequadamente e evitando longos turnos de trabalho.


Abstract In December 2019, a new human coronavirus, called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or coronavirus disease 2019 (COVID-19) by the World Health Organization, emerged in the city of Wuhan, China. Spreading globally, it is now considered pandemic, with approximately 3 million cases worldwide at the end of April. Its symptoms include fever, cough, and headache, but the main one is shortness of breath. In turn, it is believed that there is a relationship between COVID-19 and damage to the heart muscle, and hypertensive and diabetic patients, for example, seem to have worse prognosis. Therefore, COVID-19 may worsen in individuals with underlying adverse conditions, and a not negligible number of patients hospitalized with this virus had cardiovascular or cerebrovascular diseases. Systemic inflammatory response and immune system disorders during disease progression may be behind this association. In addition, the virus uses angiotensin-converting enzyme (ACE) receptors, more precisely ACE2, to penetrate the cell; therefore, the use of ACE inhibitor drugs and angiotensin receptor blockers could cause an increase in these receptors, thus facilitating the entry of the virus into the cell. There is, however, no scientific evidence to support the interruption of these drugs. Since they are fundamental for certain chronic diseases, the risk and benefit of their withdrawal in this scenario should be carefully weighed. Finally, cardiologists and health professionals should be aware of the risks of infection and protect themselves as much as possible, sleeping properly and avoiding long working hours.


Assuntos
Humanos , Pneumonia Viral/complicações , Doenças Cardiovasculares/virologia , Infecções por Coronavirus/complicações , Sistema Cardiovascular/virologia , Fatores de Risco , Infecções por Coronavirus , Peptidil Dipeptidase A/fisiologia , Pandemias , Betacoronavirus
16.
J Nephrol ; 33(2): 251-266, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31865607

RESUMO

OBJECTIVE: Patients with end-stage renal disease (ESRD) undergoing hemodialysis may have reduced dialysis adequacy (Kt/V), low cardiorespiratory fitness, and worse prognosis. Different types of intradialytic training (IDT) may serve as an adjunct therapy for the management of the ESRD. This systematic review and meta-analysis aimed to assess the impact of different types of IDT on clinical outcomes and functional parameters in ESRD. METHODS: PubMed, Embase, CINAHL, Cochrane CENTRAL, Scopus, SPORTDiscus, and Google Scholar were searched for randomized clinical trials in adult patients with ESRD which compared IDT with usual care (UC), without language restrictions and published up to July 2019; a handsearch of references was also performed. Certainty of evidence was assessed using GRADE, and risk of bias in primary studies with the RoB 1.0 tool. RESULTS: Fifty studies were included (n = 1757). Compared to UC, aerobic IDT improved Kt/V (WMD = 0.08), VO2peak (WMD = 2.07 mL/kg/min), 6-minute walk test (6MWT) distance (64.98 m), reduced systolic blood pressure (- 10.07 mmHg) and C-reactive protein (- 3.28 mg/L). Resistance training increased 6MWT distance (68.50 m). Combined training increased VO2peak (5.41 mL/kg/min) and reduced diastolic blood pressure (- 5.76 mmHg). Functional electrostimulation (FES) and inspiratory muscle training (IMT) improved 6MWT distance (54.14 m and 117.62 m, respectively). There was no impact on total cholesterol, interleukin-6, or hemoglobin levels. There was no difference in incidence of adverse events between the IDT and control groups. The certainty of evidence was variable according to the GRADE scale, with most outcomes rated very low certainty. The risk of bias assessment of primary studies showed unclear risk in most. CONCLUSIONS: Aerobic, resistance, and combined training during hemodialysis, as well as FES and IMT, demonstrated to be effective for the treatment of the patient with ESRD. Our data should be interpreted in light of the unclear risk of bias of most evaluated articles and the low to very low certainty of evidence for evaluated outcomes. PROSPERO REGISTRATION ID: CRD42017081338. DATA SHARING REPOSITORY: https://osf.io/fpj54/.


Assuntos
Exercício Físico , Falência Renal Crônica/terapia , Diálise Renal , Humanos
17.
Arq. bras. cardiol ; 113(6): 1139-1148, Dec. 2019. graf
Artigo em Inglês | LILACS | ID: biblio-1055070

RESUMO

Abstract Obesity associated with systemic inflammation induces insulin resistance (IR), with consequent chronic hyperglycemia. A series of reactions are involved in this process, including increased release of proinflammatory cytokines, and activation of c-Jun N-terminal kinase (JNK), nuclear factor-kappa B (NF-κB) and toll-like receptor 4 (TLR4) receptors. Among the therapeutic tools available nowadays, physical exercise (PE) has a known hypoglycemic effect explained by complex molecular mechanisms, including an increase in insulin receptor phosphorylation, in AMP-activated protein kinase (AMPK) activity, in the Ca2+/calmodulin-dependent protein kinase kinase (CaMKK) pathway, with subsequent activation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), Rac1, TBC1 domain family member 1 and 4 (TBC1D1 and TBC1D4), in addition to a variety of signaling molecules, such as GTPases, Rab and soluble N-ethylmaleimide-sensitive factor attached protein receptor (SNARE) proteins. These pathways promote greater translocation of GLUT4 and consequent glucose uptake by the skeletal muscle. Phosphoinositide-dependent kinase (PDK), atypical protein kinase C (aPKC) and some of its isoforms, such as PKC-iota/lambda also seem to play a fundamental role in the transport of glucose. In this sense, the association between autophagy and exercise has also demonstrated a relevant role in the uptake of muscle glucose. Insulin, in turn, uses a phosphoinositide 3-kinase (PI3K)-dependent mechanism, while exercise signal may be triggered by the release of calcium from the sarcoplasmic reticulum. The objective of this review is to describe the main molecular mechanisms of IR and the relationship between PE and glucose uptake.


Resumo A obesidade associada à inflamação sistêmica induz resistência à insulina (RI), com consequente hiperglicemia crônica. Este processo envolve o aumento na liberação de citocinas pró-inflamatórias, ativação da enzima c-Jun N-terminal cinase (JNK), do fator nuclear kappa-B (NF-κB) e dos receptores do tipo Toll 4 (TLR4). Dentre as ferramentas terapêuticas disponíveis, o exercício físico (EF) tem efeito hipoglicemiante conhecido, explicado por mecanismos moleculares complexos. Dentre eles, ocorre aumento na fosforilação do receptor da insulina, na atividade da proteína quinase ativada por AMP (AMPK), na via da proteína cinase cinase dependente de Ca+2/calmodulina (CaMKK), com posterior ativação do coativador-1α do receptor ativado por proliferador do peroxissoma (PGC-1α), proteínas Rac1, TBC1 membro das famílias de domínio 1 e 4 (TBC1D1 e TBC1D4), além de uma variedade de moléculas de sinalização, como as proteínas GTPases, Rab e proteína solúvel de fusão sensível a N-etil-maleimida (SNARE); estas vias promovem maior translocação de transportador de glicose do tipo 4 (GLUT4) e consequente captação de glicose pelo músculo esquelético. A cinase fosfatidilinositol-dependente (PDK), proteína quinase C atípica (aPKC) e algumas das suas isoformas, como a PKC-iota/lambda também parecem desempenhar papel fundamental no transporte de glicose. Nesse sentido, a associação entre autofagia e EF também tem demonstrado papel relevante na captação de glicose muscular. A insulina, por sua vez, utiliza um mecanismo dependente da fosfatidilinositol-3-quinase (PI3K), enquanto que o sinal do EF pode ter início mediante liberação de cálcio pelo retículo sarcoplasmático e concomitante ativação da AMPK. O objetivo desta revisão é descrever os principais mecanismos moleculares da RI e da relação entre o EF e a captação de glicose.


Assuntos
Humanos , Resistência à Insulina , Exercício Físico , Hiperglicemia/metabolismo , Hiperglicemia/terapia , Inflamação/metabolismo , Inflamação/terapia , Fosforilação , Transportador de Glucose Tipo 4 , Obesidade
19.
Arq. bras. cardiol ; 113(2): 274-281, Aug. 2019. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1019396

RESUMO

Abstract Dilated cardiomyopathy (DCM) is a clinical syndrome characterized by left ventricular dilatation and contractile dysfunction. It is the most common cause of heart failure in young adults. The advent of next-generation sequencing has contributed to the discovery of a large amount of genomic data related to DCM. Mutations involving genes that encode cytoskeletal proteins, the sarcomere, and ion channels account for approximately 40% of cases previously classified as idiopathic DCM. In this scenario, geneticists and cardiovascular genetics specialists have begun to work together, building knowledge and establishing more accurate diagnoses. However, proper interpretation of genetic results is essential and multidisciplinary teams dedicated to the management and analysis of the obtained information should be considered. In this review, we approach genetic factors associated with DCM and their prognostic relevance and discuss how the use of genetic testing, when well recommended, can help cardiologists in the decision-making process.


Resumo A miocardiopatia dilatada (MCD) é uma síndrome caracterizada por dilatação ventricular esquerda e disfunção contrátil, sendo considerada a causa mais comum de insuficiência cardíaca em adultos jovens. O uso do sequenciamento de nova geração tem contribuído com a descoberta de uma grande quantidade de dados genômicos relacionados à MCD, identificando mutações que envolvem genes que codificam proteínas do citoesqueleto, sarcômero e canais iônicos, os quais são responsáveis por aproximadamente 40% dos casos classificados como MCD idiopática. Nesse cenário, geneticistas e especialistas em genética cardiovascular passaram a atuar em conjunto, agregando conhecimento e estabelecendo diagnósticos mais precisos. No entanto, é fundamental interpretar corretamente os resultados genéticos, sendo necessário criar e fomentar equipes multidisciplinares dedicadas à gestão e análise das informações coletadas. Nesta revisão, abordamos os fatores genéticos associados à MCD, aspectos prognósticos, além de discutirmos como o emprego dos testes genéticos, quando bem indicados, pode ser útil na tomada de decisão na prática clínica dos cardiologistas.


Assuntos
Humanos , Masculino , Adulto , Cardiomiopatia Dilatada/genética , Testes Genéticos/métodos , Fenótipo , Prognóstico , Cardiomiopatia Dilatada/diagnóstico , Mutação
20.
Arq. bras. cardiol ; 112(6): 775-781, Jun. 2019. tab
Artigo em Inglês | LILACS | ID: biblio-1011221

RESUMO

Abstract Background: Cardiovascular disease (CVD) is the leading cause of death worldwide. Physical activity (PA) and appropriate diet, if adopted in childhood and adolescence, may reduce the CVD burden in later life. The Olympic Experimental Gymnasium (OEG) project was implemented to increase the PA levels of students by means of regular physical exercise and healthy eating habits. Objectives: To estimate and compare the prevalence of CVD risk factors in OEG schools versus regular schools (RSch) and to examine associations between the school environment and CVD risk factors. Methods: In this cross-sectional study with a comparator group, adolescents aged 12-13 years attending three OEG schools (n = 719) and three RSch (n = 394) were evaluated after one year of the ongoing program to estimate the prevalence of overweight, pre-hypertension/hypertension, altered glycemia, and lipid profile. An α level of 0.05 was set for statistical analysis. Results: RSch students had higher odds to have high blood pressure (OR 1.86, 1.36-2.54) and to be overweight (OR 1.49, 1.13-1.98) than OEG students. Glucose levels were not altered in most cases regardless of school type, and no differences were found in lipid profile. In the sensitivity analysis stratified by gender, girls from RSch were more likely to have high body mass index than boys. Conclusions: Exposure of adolescents to the OEG policies was positively associated with an important reduction in CVD risk factors, including high blood pressure and overweight.


Resumo Fundamento: A doença cardiovascular (DCV) é a principal causa de morte em todo o mundo. A atividade física (AF) e uma dieta adequada, quando adotadas na infância e na adolescência, podem reduzir a carga da DCV na fase adulta. O projeto "Ginásio Experimental Olímpico (GEO)" foi implementado para aumentar os níveis de AF dos estudantes por meio de AF regular e hábitos alimentares saudáveis. Objetivos: estimar e comparar a prevalência dos fatores de risco para DCV em GEOs versus escolas regulares (ERs), e avaliar associações entre o meio escolar e os fatores de risco cardiovascular. Métodos: Neste estudo transversal que incluiu um grupo de comparação, estudantes com idade entre 12 e 13 anos de três GEOs (n = 719) e três ERs (n = 394) foram avaliados após um ano de participação no programa para estimar a prevalência de sobrepeso, pré-hipertensão/hipertensão, e de glicemia e perfil lipídico alterados. Um α de 0,05 foi usado para inferências estatísticas. Resultados: Estudantes de ERs apresentaram maior chance de serem hipertensos (OR 1,86; 1,36-2,54) e apresentarem sobrepeso (OR 1,49; 1,13-1,98) que estudantes de GEOs. A glicemia não estava alterada na maioria dos casos, independentemente do tipo da escola, e não houve diferenças quanto ao perfil lipídico. Na análise de sensibilidade estratificada por gênero, estudantes do sexo feminino das ERs apresentaram maior probabilidade de apresentarem índice de massa corporal elevado que os do sexo masculino. Conclusão: A exposição dos adolescentes às políticas adotadas pelos GEOs associou-se positivamente com uma importante redução nos fatores de risco para DCV, incluindo hipertensão e sobrepeso.


Assuntos
Humanos , Masculino , Feminino , Criança , Adolescente , Esportes/estatística & dados numéricos , Estudantes/estatística & dados numéricos , Doenças Cardiovasculares/prevenção & controle , Doenças Cardiovasculares/etiologia , Prevalência , Estudos Transversais , Fatores de Risco , Estilo de Vida Saudável
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