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1.
Cochrane Database Syst Rev ; 10: CD011064, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33000470

RESUMO

BACKGROUND: Calcium channel blockers (CCBs) are used to manage hypertension which is highly prevalent among people with chronic kidney disease (CKD). The treatment for hypertension is particularly challenging in people undergoing dialysis. OBJECTIVES: To assess the benefits and harms of calcium channel blockers in patients with chronic kidney disease requiring dialysis. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies to 27 April 2020 through contact with the Information Specialist using search terms relevant to this review. Studies in the Specialised Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: All randomised controlled trials (RCTs) and quasi-RCTs that compared any type of CCB with other CCB, different doses of the same CCB, other antihypertensives, control or placebo were included. The minimum study duration was 12 weeks. DATA COLLECTION AND ANALYSIS: Two authors independently assessed study quality and extracted data. Statistical analyses were performed using a random-effects model and results expressed as risk ratio (RR), risk difference (RD) or mean difference (MD) with 95% confidence intervals (CI). MAIN RESULTS: This review included 13 studies (24 reports) randomising 1459 participants treated with long-term haemodialysis. Nine studies were included in the meta-analysis (622 participants). No studies were performed in children or in those undergoing peritoneal dialysis. Overall, risk of bias was assessed as unclear to high across most domains. Random sequence generation and allocation concealment were at low risk of bias in eight and one studies, respectively. Two studies reported low risk methods for blinding of participants and investigators, and outcome assessment was blinded in 10 studies. Three studies were at low risk of attrition bias, eight studies were at low risk of selective reporting bias, and five studies were at low risk of other potential sources of bias. Overall, the certainty of the evidence was low to very low for all outcomes. No events were reported for cardiovascular death in any of the comparisons. Other side effects were rarely reported and studies were not designed to measure costs. Five studies (451 randomised adults) compared dihydropyridine CCBs to placebo or no treatment. Dihydropyridine CCBs may decrease predialysis systolic (1 study, 39 participants: MD -27.00 mmHg, 95% CI -43.33 to -10.67; low certainty evidence) and diastolic blood pressure level (2 studies, 76 participants; MD -13.56 mmHg, 95% CI -19.65 to -7.48; I2 = 0%, low certainty evidence) compared to placebo or no treatment. Dihydropyridine CCBs may make little or no difference to occurrence of intradialytic hypotension (2 studies, 287 participants; RR 0.54, 95% CI 0.25 to 1.15; I2 = 0%, low certainty evidence) compared to placebo or no treatment. Other side effects were not reported. Eight studies (1037 randomised adults) compared dihydropyridine CCBs to other antihypertensives. Dihydropyridine CCBs may make little or no difference to predialysis systolic (4 studies, 180 participants: MD 2.44 mmHg, 95% CI -3.74 to 8.62; I2 = 0%, low certainty evidence) and diastolic blood pressure (4 studies, 180 participants: MD 1.49 mmHg, 95% CI -2.23 to 5.21; I2 = 0%, low certainty evidence) compared to other antihypertensives. There was no evidence of a difference in the occurrence of intradialytic hypotension (1 study, 92 participants: RR 2.88, 95% CI 0.12 to 68.79; very low certainty evidence) between dihydropyridine CCBs to other antihypertensives. Other side effects were not reported. Dihydropyridine CCB may make little or no difference to predialysis systolic (1 study, 40 participants: MD -4 mmHg, 95% CI -11.99 to 3.99; low certainty evidence) and diastolic blood pressure (1 study, 40 participants: MD -3.00 mmHg, 95% CI -7.06 to 1.06; low certainty evidence) compared to non-dihydropyridine CCB. There was no evidence of a difference in other side effects (1 study, 40 participants: RR 0.13, 95% CI 0.01 to 2.36; very low certainty evidence) between dihydropyridine CCB and non-dihydropyridine CCB. Intradialytic hypotension was not reported. AUTHORS' CONCLUSIONS: The benefits of CCBs over other antihypertensives on predialysis blood pressure levels and intradialytic hypotension among people with CKD who required haemodialysis were uncertain. Effects of CCBs on other side effects and cardiovascular death also remain uncertain. Dihydropyridine CCBs may decrease predialysis systolic and diastolic blood pressure level compared to placebo or no treatment. No studies were identified in children or peritoneal dialysis. Available studies have not been designed to measure the effects on costs. The shortcomings of the studies were that they recruited very few participants, had few events, had very short follow-up periods, some outcomes were not reported, and the reporting of outcomes such as changes in blood pressure was not done uniformly across studies. Well-designed RCTs, conducted in both adults and children with CKD requiring both haemodialysis and peritoneal dialysis, evaluating both dihydropyridine and non-dihydropyridine CCBs against other antihypertensives are required. Future research should be focused on outcomes relevant to patients (including death and cardiovascular disease), blood pressure changes, risk of side effects and healthcare costs to assist decision-making in clinical practice.


Assuntos
Anti-Hipertensivos/uso terapêutico , Bloqueadores dos Canais de Cálcio/uso terapêutico , Di-Hidropiridinas/uso terapêutico , Hipertensão/tratamento farmacológico , Diálise Renal , Insuficiência Renal Crônica/terapia , Adulto , Viés , Pressão Sanguínea/efeitos dos fármacos , Bloqueadores dos Canais de Cálcio/efeitos adversos , Di-Hidropiridinas/efeitos adversos , Humanos , Hipotensão/induzido quimicamente , Ensaios Clínicos Controlados Aleatórios como Assunto , Insuficiência Renal Crônica/complicações
2.
Cochrane Database Syst Rev ; 10: CD007004, 2020 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-33107592

RESUMO

BACKGROUND: Treatment with angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) is used to reduce proteinuria and retard the progression of chronic kidney disease (CKD). However, resolution of proteinuria may be incomplete with these therapies and the addition of an aldosterone antagonist may be added to further prevent progression of CKD. This is an update of a Cochrane review first published in 2009 and updated in 2014. OBJECTIVES: To evaluate the effects of aldosterone antagonists (selective (eplerenone), non-selective (spironolactone or canrenone), or non-steroidal mineralocorticoid antagonists (finerenone)) in adults who have CKD with proteinuria (nephrotic and non-nephrotic range) on: patient-centred endpoints including kidney failure (previously know as end-stage kidney disease (ESKD)), major cardiovascular events, and death (any cause); kidney function (proteinuria, estimated glomerular filtration rate (eGFR), and doubling of serum creatinine); blood pressure; and adverse events (including hyperkalaemia, acute kidney injury, and gynaecomastia). SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 13 January 2020 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal, and ClinicalTrials.gov. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs that compared aldosterone antagonists in combination with ACEi or ARB (or both) to other anti-hypertensive strategies or placebo in participants with proteinuric CKD. DATA COLLECTION AND ANALYSIS: Two authors independently assessed study quality and extracted data. Data were summarised using random effects meta-analysis. We expressed summary treatment estimates as a risk ratio (RR) for dichotomous outcomes and mean difference (MD) for continuous outcomes, or standardised mean difference (SMD) when different scales were used together with their 95% confidence interval (CI). Risk of bias were assessed using the Cochrane tool. Evidence certainty was evaluated using GRADE. MAIN RESULTS: Forty-four studies (5745 participants) were included. Risk of bias in the evaluated methodological domains were unclear or high risk in most studies. Adequate random sequence generation was present in 12 studies, allocation concealment in five studies, blinding of participant and investigators in 18 studies, blinding of outcome assessment in 15 studies, and complete outcome reporting in 24 studies. All studies comparing aldosterone antagonists to placebo or standard care were used in addition to an ACEi or ARB (or both). None of the studies were powered to detect differences in patient-level outcomes including kidney failure, major cardiovascular events or death. Aldosterone antagonists had uncertain effects on kidney failure (2 studies, 84 participants: RR 3.00, 95% CI 0.33 to 27.65, I² = 0%; very low certainty evidence), death (3 studies, 421 participants: RR 0.58, 95% CI 0.10 to 3.50, I² = 0%; low certainty evidence), and cardiovascular events (3 studies, 1067 participants: RR 0.95, 95% CI 0.26 to 3.56; I² = 42%; low certainty evidence) compared to placebo or standard care. Aldosterone antagonists may reduce protein excretion (14 studies, 1193 participants: SMD -0.51, 95% CI -0.82 to -0.20, I² = 82%; very low certainty evidence), eGFR (13 studies, 1165 participants, MD -3.00 mL/min/1.73 m², 95% CI -5.51 to -0.49, I² = 0%, low certainty evidence) and systolic blood pressure (14 studies, 911 participants: MD -4.98 mmHg, 95% CI -8.22 to -1.75, I² = 87%; very low certainty evidence) compared to placebo or standard care. Aldosterone antagonists probably increase the risk of hyperkalaemia (17 studies, 3001 participants: RR 2.17, 95% CI 1.47 to 3.22, I² = 0%; moderate certainty evidence), acute kidney injury (5 studies, 1446 participants: RR 2.04, 95% CI 1.05 to 3.97, I² = 0%; moderate certainty evidence), and gynaecomastia (4 studies, 281 participants: RR 5.14, 95% CI 1.14 to 23.23, I² = 0%; moderate certainty evidence) compared to placebo or standard care. Non-selective aldosterone antagonists plus ACEi or ARB had uncertain effects on protein excretion (2 studies, 139 participants: SMD -1.59, 95% CI -3.80 to 0.62, I² = 93%; very low certainty evidence) but may increase serum potassium (2 studies, 121 participants: MD 0.31 mEq/L, 95% CI 0.17 to 0.45, I² = 0%; low certainty evidence) compared to diuretics plus ACEi or ARB. Selective aldosterone antagonists may increase the risk of hyperkalaemia (2 studies, 500 participants: RR 1.62, 95% CI 0.66 to 3.95, I² = 0%; low certainty evidence) compared ACEi or ARB (or both). There were insufficient studies to perform meta-analyses for the comparison between non-selective aldosterone antagonists and calcium channel blockers, selective aldosterone antagonists plus ACEi or ARB (or both) and nitrate plus ACEi or ARB (or both), and non-steroidal mineralocorticoid antagonists and selective aldosterone antagonists. AUTHORS' CONCLUSIONS: The effects of aldosterone antagonists when added to ACEi or ARB (or both) on the risks of death, major cardiovascular events, and kidney failure in people with proteinuric CKD are uncertain. Aldosterone antagonists may reduce proteinuria, eGFR, and systolic blood pressure in adults who have mild to moderate CKD but may increase the risk of hyperkalaemia, acute kidney injury and gynaecomastia when added to ACEi and/or ARB.


Assuntos
Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Falência Renal Crônica/tratamento farmacológico , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Proteinúria/tratamento farmacológico , Viés , Bloqueadores dos Canais de Cálcio/uso terapêutico , Canrenona/uso terapêutico , Progressão da Doença , Eplerenona/uso terapêutico , Humanos , Hiperpotassemia/induzido quimicamente , Hiperpotassemia/prevenção & controle , Antagonistas de Receptores de Mineralocorticoides/efeitos adversos , Naftiridinas/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Espironolactona/efeitos adversos , Espironolactona/análogos & derivados , Espironolactona/uso terapêutico
3.
Lancet ; 396(10253): 759-769, 2020 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-32871100

RESUMO

BACKGROUND: Cardiac muscle hypercontractility is a key pathophysiological abnormality in hypertrophic cardiomyopathy, and a major determinant of dynamic left ventricular outflow tract (LVOT) obstruction. Available pharmacological options for hypertrophic cardiomyopathy are inadequate or poorly tolerated and are not disease-specific. We aimed to assess the efficacy and safety of mavacamten, a first-in-class cardiac myosin inhibitor, in symptomatic obstructive hypertrophic cardiomyopathy. METHODS: In this phase 3, randomised, double-blind, placebo-controlled trial (EXPLORER-HCM) in 68 clinical cardiovascular centres in 13 countries, patients with hypertrophic cardiomyopathy with an LVOT gradient of 50 mm Hg or greater and New York Heart Association (NYHA) class II-III symptoms were assigned (1:1) to receive mavacamten (starting at 5 mg) or placebo for 30 weeks. Visits for assessment of patient status occurred every 2-4 weeks. Serial evaluations included echocardiogram, electrocardiogram, and blood collection for laboratory tests and mavacamten plasma concentration. The primary endpoint was a 1·5 mL/kg per min or greater increase in peak oxygen consumption (pVO2) and at least one NYHA class reduction or a 3·0 mL/kg per min or greater pVO2 increase without NYHA class worsening. Secondary endpoints assessed changes in post-exercise LVOT gradient, pVO2, NYHA class, Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (KCCQ-CSS), and Hypertrophic Cardiomyopathy Symptom Questionnaire Shortness-of-Breath subscore (HCMSQ-SoB). This study is registered with ClinicalTrials.gov, NCT03470545. FINDINGS: Between May 30, 2018, and July 12, 2019, 429 adults were assessed for eligibility, of whom 251 (59%) were enrolled and randomly assigned to mavacamten (n=123 [49%]) or placebo (n=128 [51%]). 45 (37%) of 123 patients on mavacamten versus 22 (17%) of 128 on placebo met the primary endpoint (difference +19·4%, 95% CI 8·7 to 30·1; p=0·0005). Patients on mavacamten had greater reductions than those on placebo in post-exercise LVOT gradient (-36 mm Hg, 95% CI -43·2 to -28·1; p<0·0001), greater increase in pVO2 (+1·4 mL/kg per min, 0·6 to 2·1; p=0·0006), and improved symptom scores (KCCQ-CSS +9·1, 5·5 to 12·7; HCMSQ-SoB -1·8, -2·4 to -1·2; p<0·0001). 34% more patients in the mavacamten group improved by at least one NYHA class (80 of 123 patients in the mavacamten group vs 40 of 128 patients in the placebo group; 95% CI 22·2 to 45·4; p<0·0001). Safety and tolerability were similar to placebo. Treatment-emergent adverse events were generally mild. One patient died by sudden death in the placebo group. INTERPRETATION: Treatment with mavacamten improved exercise capacity, LVOT obstruction, NYHA functional class, and health status in patients with obstructive hypertrophic cardiomyopathy. The results of this pivotal trial highlight the benefits of disease-specific treatment for this condition. FUNDING: MyoKardia.


Assuntos
Benzilaminas/uso terapêutico , Miosinas Cardíacas/antagonistas & inibidores , Cardiomiopatia Hipertrófica/tratamento farmacológico , Uracila/análogos & derivados , Antagonistas Adrenérgicos beta/uso terapêutico , Idoso , Benzilaminas/efeitos adversos , Bloqueadores dos Canais de Cálcio/uso terapêutico , Cardiomiopatia Hipertrófica/fisiopatologia , Fármacos Cardiovasculares/uso terapêutico , Método Duplo-Cego , Tolerância ao Exercício/fisiologia , Feminino , Hemodinâmica/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Consumo de Oxigênio/fisiologia , Avaliação de Resultados da Assistência ao Paciente , Uracila/efeitos adversos , Uracila/uso terapêutico
4.
Rev Med Suisse ; 16(706): 1680-1683, 2020 Sep 16.
Artigo em Francês | MEDLINE | ID: mdl-32936548

RESUMO

Hypertension is a common clinical problem in patients with cancer. This is explained by its high prevalence in the general population, by the improvement in life expectancy in oncology patients thanks to the progress of anti-cancer therapies, but also by cancer therapy, which is sometimes burdened with cardiovascular toxicity. Early detection of hypertension and proper management are crucial to ensure the continuation of oncology treatment and to protect patients from the consequences of hypertension. Renin-angiotensin system blockers and calcium channel blockers are the first-line treatments.


Assuntos
Anti-Hipertensivos/uso terapêutico , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Neoplasias/complicações , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Bloqueadores dos Canais de Cálcio/uso terapêutico , Humanos , Sistema Renina-Angiotensina
5.
Pediatr Cardiol ; 41(7): 1301-1318, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32915293

RESUMO

Alterations in blood pressure are common during the perioperative period in infants and children. Perioperative hypertension may be the result of renal failure, volume overload, or activation of the sympathetic nervous system. Concerns regarding end-organ effects or postoperative bleeding may mandate regulation of blood pressure. During the perioperative period, various pharmacologic agents have been used for blood pressure control including sodium nitroprusside, nitroglycerin, ß-adrenergic antagonists, fenoldopam, and calcium channel antagonists. The following manuscript outlines the commonly used pharmacologic agents for perioperative BP including dosing regimens and adverse effect profiles. Previously published clinical trials are discussed and efficacy in the perioperative period reviewed.


Assuntos
Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Adolescente , Antagonistas Adrenérgicos beta/efeitos adversos , Antagonistas Adrenérgicos beta/farmacologia , Antagonistas Adrenérgicos beta/uso terapêutico , Anti-Hipertensivos/efeitos adversos , Anti-Hipertensivos/farmacologia , Bloqueadores dos Canais de Cálcio/efeitos adversos , Bloqueadores dos Canais de Cálcio/farmacologia , Bloqueadores dos Canais de Cálcio/uso terapêutico , Criança , Pré-Escolar , Fenoldopam/efeitos adversos , Fenoldopam/farmacologia , Fenoldopam/uso terapêutico , Humanos , Hipertensão/etiologia , Lactente , Masculino , Nitroprussiato/efeitos adversos , Nitroprussiato/farmacologia , Nitroprussiato/uso terapêutico , Período Perioperatório , Insuficiência Renal/complicações , Resultado do Tratamento
6.
PLoS One ; 15(9): e0239039, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32915892

RESUMO

BACKGROUND: Beta-blockers are often not the preferred treatment for patients with vasospastic angina. However, nebivolol, beta-blocker with nitric oxide-releasing effect, could theoretically improve coronary vasospasm. We compared nebivolol versus diltiazem in improving coronary vasospasm and quality of life in patients with hypertensive vasospastic angina during a 12-week follow-up. METHODS: Fifty-one hypertensive patients with documented coronary vasospasm were randomly allocated into 3 treatment groups: (1) Nebivolol Group (5mg for 2 weeks/10mg for 10 weeks); (2) Diltiazem Group (90mg for 2 weeks/180mg for 10 weeks); (3) Low-dose Combination Group (2.5mg + 45mg for 2 weeks/5mg + 90mg for 10 weeks). The primary endpoint was to compare the percent changes in coronary vasospasm at 12 weeks from baseline among the 3 groups. The secondary endpoints included changes in quality of life based on the Seattle Angina Questionnaire and changes in blood pressure at 12 weeks from baseline. RESULTS: Significant improvements in coronary vasospasm were found in all groups; however, the improvement in percent changes in coronary artery spasm was greatest in the Diltiazem Group (50.4±8.8% vs. 67.8±12.8% vs. 46.8±12.3%, Nebivolol Group vs. Diltiazem Group p = 0.008; Nebivolol Group vs. Low-dose Combination Group p = 0.999; Diltiazem Group vs. Low-dose Combination Group p = 0.017). The overall Seattle Angina Questionnaire scores were significantly elevated at 12 weeks compared to the baseline in entire study population. There were no significant differences between the three groups in the overall Seattle Angina Questionnaire score changes and blood pressure changes. CONCLUSIONS: Both nebivolol and diltiazem showed significant coronary vasospasm reduction effect, but the effect was greater for diltiazem.


Assuntos
Angina Pectoris/tratamento farmacológico , Vasoespasmo Coronário/tratamento farmacológico , Diltiazem/uso terapêutico , Hipertensão/tratamento farmacológico , Nebivolol/uso terapêutico , Antagonistas Adrenérgicos beta/administração & dosagem , Antagonistas Adrenérgicos beta/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Angina Pectoris/complicações , Angina Pectoris/fisiopatologia , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Bloqueadores dos Canais de Cálcio/administração & dosagem , Bloqueadores dos Canais de Cálcio/uso terapêutico , Angiografia Coronária , Vasoespasmo Coronário/etiologia , Vasoespasmo Coronário/fisiopatologia , Citocinas/sangue , Diltiazem/administração & dosagem , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Hipertensão/complicações , Hipertensão/fisiopatologia , Mediadores da Inflamação/sangue , Masculino , Pessoa de Meia-Idade , Nebivolol/administração & dosagem , Óxido Nítrico/metabolismo , Projetos Piloto , Estudos Prospectivos , Qualidade de Vida , Vasodilatação/efeitos dos fármacos
7.
J Med Internet Res ; 22(8): e20773, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32759101

RESUMO

BACKGROUND: A novel disease poses special challenges for informatics solutions. Biomedical informatics relies for the most part on structured data, which require a preexisting data or knowledge model; however, novel diseases do not have preexisting knowledge models. In an emergent epidemic, language processing can enable rapid conversion of unstructured text to a novel knowledge model. However, although this idea has often been suggested, no opportunity has arisen to actually test it in real time. The current coronavirus disease (COVID-19) pandemic presents such an opportunity. OBJECTIVE: The aim of this study was to evaluate the added value of information from clinical text in response to emergent diseases using natural language processing (NLP). METHODS: We explored the effects of long-term treatment by calcium channel blockers on the outcomes of COVID-19 infection in patients with high blood pressure during in-patient hospital stays using two sources of information: data available strictly from structured electronic health records (EHRs) and data available through structured EHRs and text mining. RESULTS: In this multicenter study involving 39 hospitals, text mining increased the statistical power sufficiently to change a negative result for an adjusted hazard ratio to a positive one. Compared to the baseline structured data, the number of patients available for inclusion in the study increased by 2.95 times, the amount of available information on medications increased by 7.2 times, and the amount of additional phenotypic information increased by 11.9 times. CONCLUSIONS: In our study, use of calcium channel blockers was associated with decreased in-hospital mortality in patients with COVID-19 infection. This finding was obtained by quickly adapting an NLP pipeline to the domain of the novel disease; the adapted pipeline still performed sufficiently to extract useful information. When that information was used to supplement existing structured data, the sample size could be increased sufficiently to see treatment effects that were not previously statistically detectable.


Assuntos
Betacoronavirus , Bloqueadores dos Canais de Cálcio/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Hipertensão/complicações , Processamento de Linguagem Natural , Pneumonia Viral/tratamento farmacológico , Infecções por Coronavirus/complicações , Mineração de Dados , Registros Eletrônicos de Saúde , Humanos , Pandemias , Pneumonia Viral/complicações , Fatores de Tempo
8.
High Blood Press Cardiovasc Prev ; 27(5): 379-388, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32705504

RESUMO

INTRODUCTION: Structural and functional properties of the left ventricle (LV) wall have been reported to be altered in hypertension, even at early stages of the disease. Abnormal adipokine levels affect blood pressure regulation. Hypo-adiponectinaemia and hyper-leptinaemia were reported in hypertension. AIM: To evaluate the effects of valsartan versus amlodipine on LV deformation also, on plasma adiponectin and leptin levels in hypertensive individuals. METHODS: LV strain was measured by two-dimensional speckle tracking echocardiography, plasma levels of adiponectin and leptin was determined in 30 healthy individuals served as control group and in 200 hypertensive patients before and after treatment for 6 months with either valsartan 160 mg or amlodipine 10 mg. RESULTS: Compared to control group longitudinal strain was significantly affected in hypertensive patients, adiponectin was significantly lower while TNF-α, hs-CRP and leptin levels were significantly higher in hypertensive group. A significant improvement in LV functions, along with a decrease in leptin and increase in adiponectin levels in valsartan group compared to amlodipine group. CONCLUSIONS: Our results indicate that valsartan is superior to amlodipine when it comes to affecting the hormonal function of human adipose tissue. Valsartan has a beneficial effect on LV deformation and function presented in GLS.


Assuntos
Adipocinas/sangue , Anlodipino/uso terapêutico , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Bloqueadores dos Canais de Cálcio/uso terapêutico , Ecocardiografia , Hipertensão/terapia , Valsartana/uso terapêutico , Função Ventricular Esquerda/efeitos dos fármacos , Remodelação Ventricular/efeitos dos fármacos , Adiponectina/sangue , Adulto , Anlodipino/efeitos adversos , Bloqueadores do Receptor Tipo 1 de Angiotensina II/efeitos adversos , Anti-Hipertensivos/efeitos adversos , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Bloqueadores dos Canais de Cálcio/efeitos adversos , Egito , Feminino , Humanos , Hipertensão/sangue , Hipertensão/diagnóstico por imagem , Hipertensão/fisiopatologia , Leptina/sangue , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Fatores de Tempo , Resultado do Tratamento , Fator de Necrose Tumoral alfa/sangue , Valsartana/efeitos adversos
9.
ACS Chem Neurosci ; 11(15): 2145-2148, 2020 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-32662982

RESUMO

Studies have shown that the calcium ion (Ca2+) plays important roles both in Alzheimer's dementia and SARS-CoV S-mediated fusion to host cell entry. An elevated level of intracellular calcium causes neuronal dysfunction, cell death, and apoptosis. Dysregulation of calcium has also been shown to increase the production of amyloid beta (Aß) protein, the hallmark of Alzheimer's dementia. Reversely, deposition of Aß is also responsible for calcium dysregulation. On the other hand, it has been well investigated that viruses can disturb host cell Ca2+ homeostasis as well as modulate signal transduction mechanisms. Viruses can also hijack the host cell calcium channels and pumps to release more intracellular Ca2+ to utilize for their life cycle. Even though evidence has not been reported on SARS-CoV-2 concerning Ca2+ regulation, however, it has been well established that Ca2+ is essential for viral entry, viral gene replication, and virion maturation and release. Recent reports suggest that SARS-CoV needs two Ca2+ ions to fuse with the host cell at the entry step. Furthermore, some calcium channel blockers (CCBs), such as nimodipine, memantine, etc., have been reported to be effective in the treatment of dementia in Alzheimer's disease (AD) as well as have shown inhibition in various virus infections.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Betacoronavirus , Bloqueadores dos Canais de Cálcio/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Doença de Alzheimer/metabolismo , Doença de Alzheimer/psicologia , Cálcio/metabolismo , Bloqueadores dos Canais de Cálcio/química , Bloqueadores dos Canais de Cálcio/farmacologia , Canais de Cálcio/metabolismo , Infecções por Coronavirus/metabolismo , Infecções por Coronavirus/psicologia , Humanos , Pandemias , Pneumonia Viral/metabolismo , Pneumonia Viral/psicologia , Resultado do Tratamento
10.
Am J Cardiol ; 128: 75-83, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32650928

RESUMO

Highly reliable identification of adults with hypertrophic cardiomyopathy (HC) at risk for sudden death (SD) has been reported. A significant controversy remains, however, regarding the most reliable risk stratification methodology for children and adolescents with HC. The present study assesses the accuracy of SD prediction and prevention with prophylactic implantable cardioverter-defibrillators (ICDs) in young HC patients. The study group is comprised of 146 HC patients <20 years of age evaluated consecutively over 17 years with prospective risk stratification and ICD decision-making. We relied on ≥1 established individual risk markers considered major within each patient's clinical profile, based on an enhanced American College of Cardiology /American Heart Association (ACC/AHA) guidelines algorithm. Of the 60 largely asymptomatic patients implanted with primary prevention ICDs at age 15 ± 4 years, 9 (15%) experienced device therapy terminating potentially lethal ventricular tachyarrhythmias and restoring sinus rhythm at 19 ± 6 years (range 9 to 29), 5.1 ± 6.0 years after implant; 3 patients had multiple appropriate ICD discharges. The individual risk marker algorithm was associated with 100% sensitivity in predicting SD events (95%CI: 69, 100) and 63% specificity for identifying patients without events (95%CI: 54, 71). Of these patients with device therapy, massive left ventricular hypertrophy (absolute wall thickness ≥30 mm) was the most common predictor, present in 70% of patients either alone or in combination with other risk markers. Each of the 146 study patients have survived to date at 22 ± 5 years, including all 86 without ICD recommendations. In conclusion, an enhanced ACC/AHA risk stratification strategy, based on established individual risk markers, was highly reliable in prospectively predicting SD events in children and adolescents with HC, and preventing arrhythmia-based catastrophes in this susceptible high risk population.


Assuntos
Cardiomiopatia Hipertrófica/terapia , Morte Súbita Cardíaca/prevenção & controle , Desfibriladores Implantáveis , Adolescente , Antagonistas Adrenérgicos beta/uso terapêutico , Adulto , Antiarrítmicos/uso terapêutico , Bloqueadores dos Canais de Cálcio/uso terapêutico , Dispositivos de Terapia de Ressincronização Cardíaca , Cardiomiopatia Hipertrófica/complicações , Criança , Morte Súbita Cardíaca/etiologia , Disopiramida/uso terapêutico , Feminino , Humanos , Masculino , Prevenção Primária , Medição de Risco , Síncope/epidemiologia , Taquicardia Ventricular/epidemiologia , Adulto Jovem
11.
Proc Natl Acad Sci U S A ; 117(32): 19497-19506, 2020 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-32719120

RESUMO

Understanding the genetics of susceptibility to infectious agents is of great importance to our ability to combat disease. Here, we show that voltage-gated calcium channels (VGCCs) are critical for cellular binding and entry of the New World arenaviruses Junín and Tacaribe virus, suggesting that zoonosis via these receptors could occur. Moreover, we demonstrate that α1s haploinsufficiency renders cells and mice more resistant to infection by these viruses. In addition to being more resistant to infection, haploinsufficient cells and mice required a lower dosage of VGCC antagonists to block infection. These studies underscore the importance of genetic variation in susceptibility to both viruses and pharmaceutics.


Assuntos
Infecções por Arenaviridae/genética , Canais de Cálcio Tipo L/genética , Resistência à Doença/genética , Animais , Infecções por Arenaviridae/tratamento farmacológico , Arenavirus do Novo Mundo/fisiologia , Agonistas dos Canais de Cálcio/farmacologia , Agonistas dos Canais de Cálcio/uso terapêutico , Bloqueadores dos Canais de Cálcio/farmacologia , Bloqueadores dos Canais de Cálcio/uso terapêutico , Canais de Cálcio Tipo L/deficiência , Canais de Cálcio Tipo L/metabolismo , Células Cultivadas , Relação Dose-Resposta a Droga , Heterozigoto , Humanos , Camundongos , Camundongos Mutantes , Mutação , Ligação Viral/efeitos dos fármacos , Internalização do Vírus/efeitos dos fármacos
13.
Turk Kardiyol Dern Ars ; 48(4): 410-424, 2020 06.
Artigo em Inglês | MEDLINE | ID: covidwho-595169

RESUMO

OBJECTIVE: The aim of this study was to evaluate the effectiveness of plants used in the formulations of traditional Chinese medicine (TCM), which were also used in clinical trials to treat patients with the novel coronavirus COVID-19, and to assess their effects on the cardiovascular system. METHODS: A literature review of PubMed, ResearchGate, ScienceDirect, the Cochrane Library, and TCM monographs was conducted and the effects of the plants on the cardiovascular system and the mechanisms of action in COVID-19 treatment were evaluated. RESULTS: The mechanism of action, cardiovascular effects, and possible toxicity of 10 plants frequently found in TCM formulations that were used in the clinical treatment of COVID-19 were examined. CONCLUSION: TCM formulations that had been originally developed for earlier viral diseases have been used in COVID-19 treatment. Despite the effectiveness seen in laboratory and animal studies with the most commonly used plants in these formulations, the clinical studies are currently insufficient according to standard operating procedures. More clinical studies are needed to understand the safe clinical use of traditional plants.


Assuntos
Sistema Cardiovascular/efeitos dos fármacos , Infecções por Coronavirus/terapia , Medicamentos de Ervas Chinesas/uso terapêutico , Medicina Tradicional Chinesa , Pneumonia Viral/terapia , Animais , Antiarrítmicos/farmacologia , Antiarrítmicos/uso terapêutico , Antiarrítmicos/toxicidade , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/toxicidade , Anticolesterolemiantes/farmacologia , Anticolesterolemiantes/uso terapêutico , Anticolesterolemiantes/toxicidade , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Anti-Hipertensivos/toxicidade , Antivirais/farmacologia , Antivirais/uso terapêutico , Antivirais/toxicidade , Bloqueadores dos Canais de Cálcio/farmacologia , Bloqueadores dos Canais de Cálcio/uso terapêutico , Bloqueadores dos Canais de Cálcio/toxicidade , Interações Medicamentosas , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/toxicidade , Humanos , Pandemias , Inibidores da Agregação de Plaquetas/farmacologia , Inibidores da Agregação de Plaquetas/uso terapêutico , Inibidores da Agregação de Plaquetas/toxicidade , Vasodilatadores/farmacologia , Vasodilatadores/uso terapêutico , Vasodilatadores/toxicidade
14.
Turk Kardiyol Dern Ars ; 48(4): 410-424, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32519978

RESUMO

OBJECTIVE: The aim of this study was to evaluate the effectiveness of plants used in the formulations of traditional Chinese medicine (TCM), which were also used in clinical trials to treat patients with the novel coronavirus COVID-19, and to assess their effects on the cardiovascular system. METHODS: A literature review of PubMed, ResearchGate, ScienceDirect, the Cochrane Library, and TCM monographs was conducted and the effects of the plants on the cardiovascular system and the mechanisms of action in COVID-19 treatment were evaluated. RESULTS: The mechanism of action, cardiovascular effects, and possible toxicity of 10 plants frequently found in TCM formulations that were used in the clinical treatment of COVID-19 were examined. CONCLUSION: TCM formulations that had been originally developed for earlier viral diseases have been used in COVID-19 treatment. Despite the effectiveness seen in laboratory and animal studies with the most commonly used plants in these formulations, the clinical studies are currently insufficient according to standard operating procedures. More clinical studies are needed to understand the safe clinical use of traditional plants.


Assuntos
Sistema Cardiovascular/efeitos dos fármacos , Infecções por Coronavirus/terapia , Medicamentos de Ervas Chinesas/uso terapêutico , Medicina Tradicional Chinesa , Pneumonia Viral/terapia , Animais , Antiarrítmicos/farmacologia , Antiarrítmicos/uso terapêutico , Antiarrítmicos/toxicidade , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/toxicidade , Anticolesterolemiantes/farmacologia , Anticolesterolemiantes/uso terapêutico , Anticolesterolemiantes/toxicidade , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Anti-Hipertensivos/toxicidade , Antivirais/farmacologia , Antivirais/uso terapêutico , Antivirais/toxicidade , Bloqueadores dos Canais de Cálcio/farmacologia , Bloqueadores dos Canais de Cálcio/uso terapêutico , Bloqueadores dos Canais de Cálcio/toxicidade , Interações Medicamentosas , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/toxicidade , Humanos , Pandemias , Inibidores da Agregação de Plaquetas/farmacologia , Inibidores da Agregação de Plaquetas/uso terapêutico , Inibidores da Agregação de Plaquetas/toxicidade , Vasodilatadores/farmacologia , Vasodilatadores/uso terapêutico , Vasodilatadores/toxicidade
16.
Expert Opin Pharmacother ; 21(14): 1713-1723, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32584617

RESUMO

INTRODUCTION: Hypertension is a major and modifiable risk factor for cardiovascular disease. Its prevalence is rising as the result of population aging. Isolated systolic hypertension mostly occurs in older patients accounting for up to 80% of cases. AREAS COVERED: The authors systematically review published studies to appraise the scientific and clinical evidence supporting the role of blood pressure control in elderly patients with isolated systolic hypertension, and to assess the influence of different drug treatment regimens on outcomes. EXPERT OPINION: Antihypertensive treatment of isolated systolic hypertension significantly reduces the risk of morbidity and mortality in elderly patients. Thiazide diuretics and dihydropyridine calcium-channel blockers are the primary compounds used in randomized clinical trials. These drugs can be considered as first-line agents for the management of isolated systolic hypertension. Free or fixed combination therapy with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers and calcium-channel blockers or thiazide-like diuretics should also be considered, particularly when compelling indications such as coronary artery disease, chronic kidney disease, diabetes, and congestive heart failure coexist. There is also hot scientific debate on the optimal blood pressure target to be achieved in elderly patients with isolated systolic hypertension, but current recommendations are scarcely supported by evidence.


Assuntos
Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Bloqueadores dos Canais de Cálcio/uso terapêutico , Hipertensão/tratamento farmacológico , Inibidores de Simportadores de Cloreto de Sódio/uso terapêutico , Idoso , Antagonistas de Receptores de Angiotensina/administração & dosagem , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Anti-Hipertensivos/administração & dosagem , Bloqueadores dos Canais de Cálcio/administração & dosagem , Diabetes Mellitus/tratamento farmacológico , Quimioterapia Combinada , Humanos , Inibidores de Simportadores de Cloreto de Sódio/administração & dosagem
17.
J Korean Med Sci ; 35(25): e232, 2020 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-32597045

RESUMO

BACKGROUND: There is a controversy whether it is safe to continue renin-angiotensin system blockers in patients with coronavirus disease 2019 (COVID-19). We analyzed big data to investigate whether angiotensin-converting enzyme inhibitors and/or angiotensin II receptor blockers have any significant effect on the risk of COVID-19. Population-based cohort study was conducted based on the prescription data from nationwide health insurance records. METHODS: We investigated the 1,374,381 residents aged ≥ 40 years living in Daegu, the epicenter of the COVID-19 outbreak, between February and March 2020. Prescriptions of antihypertensive medication during the year before the outbreak were extracted from the National Health Insurance Service registry. Medications were categorized by types and stratified by the medication possession ratios (MPRs) of antihypertensive medications after controlling for the potential confounders. The risk of COVID-19 was estimated using a difference in difference analysis. RESULTS: Females, older individuals, low-income earners, and recently hospitalized patients had a higher risk of infection. Patients with higher MPRs of antihypertensive medications had a consistently lower risk of COVID-19 than those with lower MPRs of antihypertensive medications and non-users. Among patients who showed complete compliance, there was a significantly lower risk of COVID-19 for those prescribed angiotensin II receptor blockers (relative risk [RR], 0.751; 95% confidence interval [CI], 0.587-0.960) or calcium channel blockers (RR, 0.768; 95% CI, 0.601-0.980). CONCLUSION: Renin-angiotensin system blockers or other antihypertensive medications do not increase the risk of COVID-19. Patients should not stop antihypertensive medications, including renin-angiotensin system blockers, because of concerns of COVID-19.


Assuntos
Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Bloqueadores dos Canais de Cálcio/uso terapêutico , Infecções por Coronavirus/epidemiologia , Pneumonia Viral/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antagonistas de Receptores de Angiotensina/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Anti-Hipertensivos/efeitos adversos , Betacoronavirus/efeitos dos fármacos , Bloqueadores dos Canais de Cálcio/efeitos adversos , Feminino , Humanos , Hipertensão/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Pandemias , Peptidil Dipeptidase A/metabolismo , Sistema Renina-Angiotensina/efeitos dos fármacos , República da Coreia/epidemiologia
18.
Int J Mol Sci ; 21(11)2020 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-32521790

RESUMO

This study was undertaken to test two therapies for acute kidney injury (AKI) prevention, IGF-1, which is renal protective, and BTP-2, which is a calcium entry (SOCE) inhibitor. We utilized lipopolysaccharide (LPS) IP, as a systemic model of AKI and studied in five groups of animals. Three experiments showed that at 7 days: (1) LPS significantly reduced serum IGF-1 and intramuscular IGF-I in vivo gene therapy rescued this deficiency. (2) Next, at the 7-day time point, our combination therapy,compared to the untreated group,caused a significant increase in survival, which was noteworthy because all of the untreated animals died in 72 hrs. (3) The four pathways associated with inflammation, including (A) increase in cytosolic calcium, (B) elaboration of proinflammatory cytokines, (C) impairment of vascular integrity, and (D) cell injury, were adversely affected in renal tissue by LPS, using a sublethal dose of LPS. The expression of several genes was measured in each of the above pathways. The combined therapy of IGF-1 and BTP-2 caused a favorable gene expression response in all four pathways. Our current study was an AKI study, but these pathways are also involved in other types of severe inflammation, including sepsis, acute respiratory distress syndrome, and probably severe coronavirus infection.


Assuntos
Lesão Renal Aguda/patologia , Fator de Crescimento Insulin-Like I/genética , Lesão Renal Aguda/mortalidade , Lesão Renal Aguda/terapia , Animais , Cálcio/metabolismo , Bloqueadores dos Canais de Cálcio/farmacologia , Bloqueadores dos Canais de Cálcio/uso terapêutico , Citocinas/genética , Citocinas/metabolismo , Citoplasma/metabolismo , Modelos Animais de Doenças , Feminino , Expressão Gênica/efeitos dos fármacos , Terapia Genética , Fator de Crescimento Insulin-Like I/análise , Fator de Crescimento Insulin-Like I/deficiência , Rim/metabolismo , Rim/patologia , Lipopolissacarídeos/toxicidade , Camundongos , Camundongos Endogâmicos C57BL , Proteína ORAI1/antagonistas & inibidores , Proteína ORAI1/metabolismo , Taxa de Sobrevida
20.
Curr Opin Cardiol ; 35(4): 368-375, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32398603

RESUMO

PURPOSE OF REVIEW: Systemic hypertension (HTN) is a common complication arising in the heart transplant recipient. This article aims to review the most current literature and update readers on the epidemiology, pathophysiology and management of HTN in heart transplant patients. RECENT FINDINGS: In contrast to the general nontransplant hypertensive patient population, traditional risk factors, including family history of HTN, obesity and diabetes, play a minor role in the genesis of posttransplant HTN. Dysregulation in sodium and water balance, vascular stiffness, endothelial dysfunction, abnormal cardiorenal neural reflexes resulting from immunosuppression and cardiac denervation seem to be the predominant factors leading to postheart transplant HTN. Calcineurin inhibitors induced nephrotoxicity and steroid use further contributes to posttransplant HTN. SUMMARY: Owing to the paucity of data, particularly randomized controlled trials to guide the evaluation and management of HTN in the cardiac transplant patients, much of the available data come from the renal transplant population. The choice of antihypertensive should be based on timing related to transplantation and patient's comorbidities. Although calcium channel blockers and loop diuretics are the preferred agents in the early postheart transplant period, angiotensin-converting-enzyme inhibitors and angiotensin receptor blockers may be beneficial in the late postheart transplant period especially in the setting of diabetes and in the presence of proteinuria.


Assuntos
Transplante de Coração/efeitos adversos , Hipertensão/tratamento farmacológico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Bloqueadores dos Canais de Cálcio/uso terapêutico , Humanos
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