Arq Bras CardiolabcArquivos Brasileiros de CardiologiaArq. Bras. Cardiol.0066-782X1678-4170Sociedade Brasileira de Cardiologia - SBCGZL8f4W3TSrwQxCPtrqB3rfS0066-782X20250001005020050210.36660/abc.20240596abc.20240596Carta CientíficaAcupuntura na Hipertensão Arterial e Disfunção Endotelial: Um Ensaio Clínico Randomizado0009-0007-9132-2310BitencourtAmanda RodriguesConcepção e desenho da pesquisaObtenção de dadosAnálise e interpretação dos dadosObtenção de financiamentoRedação do manuscrito e Revisão crítica do manuscrito quanto ao conteúdoAnálise estatística1SousaAna Luiza LimaAnálise estatística10000-0002-5487-4649VitorinoPriscila Valverde de OliveiraAnálise estatística20000-0002-0954-4261CorreiaMikaelle CostaObtenção de dados1YoshizumiAlexandre MassaoConcepção e desenho da pesquisa30000-0002-1265-1930BarrosoWeimar Kunz SebbaConcepção e desenho da pesquisaAnálise e interpretação dos dadosObtenção de financiamentoRedação do manuscrito e Revisão crítica do manuscrito quanto ao conteúdoAnálise estatística1Universidade Federal de GoiásUnidade de Hipertensão ArterialGoiâniaGOBrasilUniversidade Federal de Goiás – Unidade de Hipertensão Arterial, Goiânia, GO – BrasilPontifícia Universidade Católica de GoiásEscola de Ciências Sociais e da SaúdeGoiâniaGOBrasilPontifícia Universidade Católica de Goiás – Escola de Ciências Sociais e da Saúde, Goiânia, GO – BrasilHospital Israelita Albert EinsteinSão PauloSPBrasilHospital Israelita Albert Einstein, São Paulo, SP – BrasilAmanda Rodrigues Bitencourt • Universidade Federal de Goiás – Unidade de Hipertensão – AV. S/N. CEP 74605-220, Setor Oeste Universitário, Goiânia, GO – Brasil E-mail: dra.amandabitencourt@gmail.com, amandabitencourt30@hotmail.com
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1702202520251221e20240596300920242611202426112024This is an open-access article distributed under the terms of the Creative Commons Attribution LicensePalavras-chaveAcupunturaHipertensãoPré-HipertensãoEndotélioIntrodução
A hipertensão arterial (HA) é um dos principais fatores de risco modificáveis para doenças cardiovasculares,1 por acarretar alterações como aumento da rigidez arterial e disfunção endotelial já em fases iniciais.2
A hiperatividade simpática e a ativação do sistema renina-angiotensina-aldosterona (SRAA) destacam-se como mecanismos fisiopatogênicos da HA, além da produção exacerbada de espécies reativas de oxigênio (ROS) e desequilíbrios na biodisponibilidade de óxido nítrico (NO).3 O aumento da permeabilidade endotelial presente em estados de baixa produção de NO explicam a correlação da HA com aterosclerose e tornam a análise da função endotelial uma ferramenta útil na avaliação do seu curso clínico.1,4,5
Apesar do vasto arsenal terapêutico disponível para seu tratamento, a HA ainda é mal controlada em todo mundo1 e as recomendações de tratamento não farmacológico devem ser feitas para todo paciente hipertenso.1,3,6 Algumas publicações apontam para o efeito benéfico da acupuntura (ACP) em pacientes hipertensos.7–16 O estímulo álgico gerado pela agulha alcança os neurônios pré-ganglionares simpáticos da medula ventrolateral rostral, bloqueia o reflexo autonômico simpatoexcitatório visceral e reduz o espasmo do músculo liso.7,17–19 Além disso, o estímulo inibe a ativação simpática mediada pela ação central do SRAA,20,21 reduz a secreção e atividade da renina e de receptores de angiotensina II19,20 e dos níveis de ROS, e ativa a NO sintase endotelial, levando ao aumento da biodisponibilidade de NO, à vasodilatação e à melhora da disfunção endotelial,7,21–24 contribuindo para o efeito da ACP no controle pressórico.7,17–24
Diante disso, este artigo descreve o método de um ensaio clínico randomizado que avaliará os efeitos antes e após 24 sessões da ACP na pressão arterial (PA) e PA central (PAC), na velocidade de onda de pulso (VOP) e na dilatação fluxo-mediada (FMD) em pacientes pré-hipertensos ou hipertensos estágio 1 em baixo risco cardiovascular.
MétodosTipo e local do estudo
Ensaio clínico randomizado, placebo controlado, simples cego e unicêntrico, cuja coleta de dados será realizada no centro de pesquisa da Unidade de Hipertensão Arterial (UHA) da Universidade Federal de Goiás (UFG).
O estudo está registrado no Registro Brasileiro de Ensaios Clínicos sob o número RBR-9qnxb9z e será realizado segundo recomendações do protocolo STRICTA/CONSORT.25 O estudo foi aprovado pelo Comitê de Ética em Pesquisa do Hospital das Clínicas da UFG, sob o número 6.244.770.
População, amostra e amostragem
A população do estudo será composta por adultos pré-hipertensos ou hipertensos estágio 1 de baixo risco cardiovascular, sem medicações anti-hipertensivas.
Serão excluídos pacientes com HA estágios 2 ou 3, com moderado ou alto risco cardiovascular, diabéticos, nefropatas, com história de doença arterial coronariana e/ou cerebrovascular, insuficiência cardíaca, tireoideopatias, condições que prejudiquem a condução aferente e eferente do estímulo nervoso, doenças psiquiátricas não controladas, discrasias sanguíneas graves, e lesões de pele e/ou condições que impossibilitem acesso aos acupontos. Gestantes e lactantes, pacientes com ou aqueles que tenham recebido tratamento anti-hipertensivo medicamentoso nos últimos seis meses ou ACP em qualquer momento da vida também serão excluídos.
A amostra foi calculada considerando a comparação de médias de dois grupos independentes de pelo menos 3 mmHg para a pressão sistólica, com um alfa de 5%, poder do teste de 90% e perda amostral de 10%; obtendo uma amostra de 25 participantes em cada grupo.10
Recrutamento e randomização dos pacientes
Os participantes serão selecionados de um banco de dados próprio da UHA, composto por encaminhamento e por campanhas de rastreamento, e avaliados em três visitas.
Visita inicial (VI)
Todos os pacientes serão avaliados por médica cardiologista e acupunturiatra por meio de anamnese e exame físico. A confirmação do estágio da HA será feita por medida da PA conforme orientações da Diretriz Brasileira de Hipertensão Arterial,1 utilizando o aparelho oscilométrico automático OMRON 1120.
Após preenchimento de critérios de inclusão e aceite em participar do estudo, todos os pacientes assinarão um Termo de Consentimento Livre e Esclarecido. Na sequência serão randomizados pelo site www.randomization.com para um dos dois grupos: intervenção (G1) e controle (G2). Todos os pacientes serão submetidos à avaliação da função endotelial por FMD e à medição da PAC e da VOP.
A avaliação da função endotelial pela FMD será realizada com o uso de um aparelho de ultrassonografia de alta resolução UNEX EF38G, o qual possui um dispositivo robótico que faz a varredura da artéria braquial no braço do paciente de forma automática, uniforme e precisa (Figura 1). O exame será realizado conforme orientações de diretrizes.26–28
Aparelho de ultrassonografia de alta resolução, UNEX EF38G.
Fonte: Acervo próprio.
As medidas da PAC e do grau de rigidez arterial serão realizadas pelo Mobil-OGraph® (IEM, Stolber, Alemanha), método oscilométrico que fornece PAC, VOP e Augmentation Index.29,30
Intervenção (G1) e controle (G2)
Nos pacientes do G1 será realizada a inserção de oito agulhas de ACP de aço inoxidável estéreis, tamanho 0,25x30 mm (Figura 2), com técnica concordante com princípios da Medicina Tradicional Chinesa31 e orientações do Colégio Médico Brasileiro de Acupuntura. O procedimento será realizado por médica acupunturiatra, em oito acupontos: PC6, IG4, C7, VC14, VC17, E36, F3, R3 (Figuras 3 e 4).
Pacientes do G2 serão tratados com oito agulhas não penetrantes (agulhas de Streitberger)32 distribuídas em tronco e membros, pela mesma médica, em oito não acupontos (Figura 5).
Agulha de Streitberger. Primeira e segunda agulhas não penetrantes.
Todos os participantes receberão duas sessões semanais, de 30 minutos, com intervalo entre elas não superior a três dias, por doze semanas consecutivas, totalizando 24 sessões. Os participantes usarão venda ocular individual para que não identifiquem visualmente em qual grupo estão alocados.
Visita final e visita de acompanhamento (VP)
Todos os pacientes participarão da visita final (VF) que será realizada após 24 sessões de ACP, e da visita de acompanhamento após 30 dias da VF. Em ambas, serão realizadas avaliação clínica e medidas da PA, da PAC, VOP e avaliação da função endotelial por FMD.
Na visita de VP, todos os pacientes serão questionados quanto ao tipo de agulha que acreditam terem recebido durante as sessões – agulha que penetra a pele (agulha de ACP) ou agulha que não penetra a pele (agulha placebo de Streitberger).
Análise estatística dos dados
As variáveis categóricas serão apresentadas com seus valores de frequência e proporção. Todas as análises de associação dessas variáveis deverão ser feitas com teste do qui-quadrado ou teste exato de Fisher, conforme adequação do tamanho da amostra. As variáveis quantitativas contínuas serão analisadas primeiramente quanto à normalidade da distribuição com aplicação do teste de Shapiro-Wilk. Serão aplicados testes paramétricos, como o teste t de Student ou o teste de Man-Whitney, e a análise univariada (ANOVA) ou o teste de Kruskal-Wallis, segundo a distribuição encontrada. Todos os testes deverão considerar um erro tipo I de 5% e 80% para erro Tipo II, com intervalo de confiança de 95%.
Conclusão
Se a eficácia da ACP para redução da PA e melhora da função endotelial for comprovada, a terapia poderá ser recomendada como modalidade terapêutica não-farmacológica para hipertensão em diretrizes futuras.
O presente estudo não teve fontes de financiamento externas.
Este artigo é parte de dissertação de mestrado de Amanda Rodrigues Bitencourt pela Universidade Federal de Goiás.
Este estudo foi aprovado pelo Comitê de Ética do Hospital das Clínicas HC/EBSERH/UFG sob o número de protocolo 6.244.770. Todos os procedimentos envolvidos nesse estudo estão de acordo com a Declaração de Helsinki de 1975, atualizada em 2013. O consentimento informado foi obtido de todos os participantes incluídos no estudo.
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Colonia: Könemann; 2000.10.36660/abc.20240596iResearch LetterAcupuncture for Essential Hypertension and Endothelial Dysfunction: A Randomized Clinical Trial0009-0007-9132-2310BitencourtAmanda RodriguesConception and design of the researchAcquisition of dataAnalysis and interpretation of the dataObtaining financingWriting of the manuscript and Critical revision of the manuscript for contentStatistical analysis1SousaAna Luiza LimaStatistical analysis10000-0002-5487-4649VitorinoPriscila Valverde de OliveiraStatistical analysis20000-0002-0954-4261CorreiaMikaelle CostaAcquisition of data1YoshizumiAlexandre MassaoConception and design of the research30000-0002-1265-1930BarrosoWeimar Kunz SebbaConception and design of the researchAnalysis and interpretation of the dataObtaining financingWriting of the manuscript and Critical revision of the manuscript for contentStatistical analysis1GoiâniaGOBrazilUniversidade Federal de Goiás – Unidade de Hipertensão Arterial, Goiânia, GO – BrazilGoiâniaGOBrazilPontifícia Universidade Católica de Goiás – Escola de Ciências Sociais e da Saúde, Goiânia, GO – BrazilSão PauloSPBrazilHospital Israelita Albert Einstein, São Paulo, SP – BrazilAmanda Rodrigues Bitencourt • Universidade Federal de Goiás - Unidade de Hipertensão – AV. S/N. Postal Code 74605-220, Setor Oeste Universitário, Goiânia, GO – Brazil E-mail: dra.amandabitencourt@gmail.com, amandabitencourt30@hotmail.com
No potential conflict of interest relevant to this article was reported.
Arterial hypertension (AH) is one of the main modifiable risk factors for cardiovascular diseases,1 as it causes increased arterial stiffness and endothelial dysfunction since early stages.2
Sympathetic hyperactivity and activation of the renin-angiotensin-aldosterone system (RAAS) are among the major pathophysiological mechanisms of AH, in addition to an overproduction of reactive oxygen species (ROS) and imbalances in the nitric oxide (NO) availability.3 The increase in endothelial permeability in response to low NO synthesis explains the correlation of AH with atherosclerosis and makes the analysis of endothelial function a useful tool for clinical assessment.1,4,5
Despite the wide availability of therapeutic options, AH is still poorly controlled worldwide1 and recommendations for non-pharmacological therapy should be given to hypertensive patients.1,3,6 Some evidence has suggested the beneficial effects of acupuncture (ACP) in hypertensive patients.7–16 The pain stimulus generated by the needle insertion reaches sympathetic preganglionic neurons of the rostral ventrolateral medulla, blocks autonomic visceral, sympathoexcitatory reflexes and reduces smooth muscle spasm.7,17–19 In addition, it inhibits sympathetic activation mediated by the RAAS system,20,21 reduces the release and activity of renin and angiotensin II receptors19,20 and levels of ROS, and activates endothelial NO synthase, increasing NO bioavailability and vasodilation and improving endothelial dysfunction,7,21,24 thereby contributing to the effects of ACP on blood pressure control.7,17–24
This article describes the methodology of a randomized clinical trial that will evaluate the effects of ACP on peripheral blood pressure, central blood pressure (CBP), pulse wave velocity (PWV) and flow-mediated dilation (FMD). These parameters were measured before and after 24 sessions of ACP in prehypertensive and stage 1 hypertensive patients at low cardiovascular risk.
MethodsStudy type and location
This will be a randomized, placebo-controlled, single-blind., single-center clinical trial; data will be collected at the research center of the Arterial Hypertension Unit of Goias Federal University (UFG).
The study is registered at the Brazilian Registry of Clinical Trials (RBR-9qnxb9z) and will be conducted following the STRICTA/CONSORT recommendations.25 The study was approved by the ethics committee of the UFG general hospital (approval number 6.244.770).
Population and sampling
Study population will consist of prehypertensive or stage 1 hypertensive adults at low cardiovascular risk that are not taking antihypertensive medications.
Patients at stage 2 or 3 AH, at moderate/high cardiovascular risk, and patients with diabetes, history of coronary arterial disease, cerebrovascular disease, heart failure thyroid diseases, conditions that may affect afferent and efferent innervations, uncontrolled psychiatric disorders, severe blood dyscrasias, and skin lesions or other conditions that make it impossible to access the ACP points will be excluded. Pregnant and lactating women, and patients who have received antihypertensive treatment in the previous six months or have ever received ACP will also be excluded.
Sample size was calculated considering the comparisons of the means of two independent groups of at less 3 mmHg for systolic pressure, with an alpha of 5%, power of the test of 90% and loss to follow-up of 10%, yielding a sample of 25 participants in each group.10
Patient recruitment and randomization
Patients will be selected from a database of the Arterial Hypertension Unit of UFG, composed by patient referral or screening campaigns, and will be assessed during three visits.
Visit 1
All patients will be seen by a cardiologist and a physician acupuncturist through history taking and physical examination. The stage of AH will be confirmed by measurement of blood pressure following the Brazilian guidelines on AH,1 using an automated oscillometric device (OMRON 1120).
After fulfilling the inclusion criteria and agreeing to participate in the study, all patients will sign an informed consent form. Subsequently, the patients will be randomized using www.randomization.com and allocated to either intervention group (G1) or control group (G2). Then, all patients will be assessed for endothelial function by FMD, and for CBP and PWV.
Assessment of endothelial function by FMD will be conducted using a high-resolution ultrasound device (UNEX ED38G), which is equipped with a robotic probe that scans through patient's brachial artery automatically, in a uniform and precise way (Figure 1). The test will be conducted following guidelines’ recommendations.26–28
High-resolution ultrasound equipment, UNEX EF38G.
Source: Authors’ archive.
Analysis of arterial stiffness and CBP will be performed using the Mobil-OGraph® (IEM, Stolber, Germany), which is an oscillometric method that estimates CBP, PWV and Augmentation Index.29,30
Intervention (G1) and control (G2)
In the G1 patients, eight stainless steel, sterile needles (0.25 x 0.30 mm) (Figure 2) will be inserted in eight points – PC6, IG4, C7, VC14, VC17, E36, F3, R3 (Figures 3 and 4). The technique will be conducted by a physician acupuncturist, following the principles of traditional Chinese medicine31 and the Brazilian Acupuncture Medical College's recommendations.
Patients in the G2 group will be treated with eight placebo needles (Streitberger needles) that do not penetrate the skin32 in eight non-ACP points throughout the trunk and limbs. The technique will be performed by the same physician (Figure 5).
Streitberger needle. First and second are non penetrate neddles.
All patients will receive two 30-minute sessions weekly, with an interval of up to three days between them, for 12 consecutive weeks (total of 24 sessions). Each participant will be blindfolded during the procedure as they will be blinded for group allocation.
Final visit and follow-up visit
All patients will be seen in a final visit (FV) after 24 ACP sessions and in a follow-up visit 30 days after the FV. In both visits, participants will undergo clinical assessment, blood pressure, CBP and PWV measurements, and FMD for assessment of endothelial function.
During the follow-up visit, all patients will be asked about the type of needle they believed that they received during the sessions – ACP needle (that penetrates the skin) vs. non-ACP/placebo needle (Streitberger needle, which does not penetrate the skin).
Statistical analysis
Categorical variables will be expressed as frequencies and proportions. Association analysis of these variables should be done by chi-square test or Fisher exact test, according to sample size. Continuous quantitative variables will be first assessed for normality distribution using the Shapiro-Wilk test. Then, parametric tests like the Student's t-test or the Mann-Whitney test and the ANOVA or the Kruskal-Wallis test will be applied according to data distribution. All tests should consider a type I error of 5% and a type II error of 80%, with a 95% confidence interval.
Conclusion
If the effectiveness of ACP in reducing blood pressure and improving endothelial function is proven, it can be suggested as a non-pharmacological therapy for hypertension in future guidelines.
There were no external funding sources for this study.
This article is part of the thesis of master submitted by Amanda Rodrigues Bitencourt, from Universidade Federal de Goiás.
This study was approved by the Ethics Committee of the Hospital das Clínicas HC/EBSERH/UFG under the protocol number 6.244.770. All the procedures in this study were in accordance with the 1975 Helsinki Declaration, updated in 2013. Informed consent was obtained from all participants included in the study.