Arq. Bras. Cardiol. Arquivos Brasileiros de Cardiologia Arq. Bras. Cardiol. 0066-782X 1678-4170 Sociedade Brasileira de Cardiologia MpLDcz6LQkG4hPZ5kpNL7JP S0066-782X2014000200021 00021 10.5935/abc.20140011 Artigo Especial I Posicionamento Brasileiro sobre Pré-Hipertensão, Hipertensão do Avental Branco e Hipertensão Mascarada: Diagnóstico e Conduta Alessi Alexandre Brandão Andréa Araujo Paiva Annelise Machado Gomes de Nogueira Armando da Rocha Feitosa Audes Gonzaga Carolina de Campos Amodeo Celso Mion Decio Souza Dilma do Socorro Moraes de Barbosa Eduardo Junior Emilton Lima Nobre Fernando Fuchs Flavio Dani Junior Hilton Chaves Schneider Jamil Cherem Gemelli João Villela-Martin José Fernando Scala Luiz Cesar Nazario Gomes Marco Antonio Mota Malachias Marcus Vinicus Bolivar Morais Nelson Siqueira de Moreira Filho Osni Passarelli Junior Oswaldo Jardim Paulo Cesar Brandão Veiga Miranda Roberto Dischinger Póvoa Rui Fuchs Sandra Cristina Baiocchi Sergio Jardim Thiago Veiga Barroso Weimar Kunz Sebba Sociedade Brasileira de Cardiologia Departamento de Hipertensão Arterial Departamento de Hipertensão Arterial da Sociedade Brasileira de Cardiologia pelos autores Correspondência: Paulo César B. Veiga Jardim, Rua 115-F, nº 135, Setor Sul. CEP 74085-300, Goiânia, GO - Brasil. E-mail: fvjardim.ufg@gmail.com, fvjardim@terra.com.br

Potencial Conflito de Interesses

Declaro não haver conflito de interesses pertinentes

 25 03 2014 102 2 110 119 13 11 2013 03 12 2013 03 12 2013 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Hipertensão / terapia Pré-Hipertensão / prevenção e controle Hipertensão do Jaleco Branco Hipertensão Mascarada Introdução

A Pressão Arterial (PA) é uma variável de grande utilidade na prática clínica. A sua medida é um procedimento simples, de baixo custo e de fácil realização, ressaltando-se a necessidade da sua obtenção tecnicamente correta, seguindo-se as recomendações das VI Diretrizes Brasileiras de Hipertensão (DBH VI)1.

A medida de consultório representa o parâmetro central para diagnóstico, tratamento e acompanhamento da Hipertensão Arterial Sistêmica (HAS) e se relaciona de forma direta, contínua e independente com o risco de eventos Cardiovasculares (CV) fatais e não fatais1 - 3.

Assim, a valorização e a intervenção sobre valores de PA mais próximos aos limites máximos de normalidade, a chamada Pré-hipertensão (PH)2, têm sido destacadas na última década, pois representam uma oportunidade importante para a prevenção da HAS estabelecida e contribuem para a redução do risco CV associado.

A medida repetida da PA no consultório permite o diagnóstico de hipertensão e normotensão. Para a melhor avaliação do comportamento da PA existem métodos que analisam a PA por meio de maior número de medidas, minimizando as interferências do meio, da situação e do observador. Essas alternativas são: Monitorização Ambulatorial da Pressão Arterial (MAPA) de 24 horas ou as medidas domiciliares da PA (monitorização residencial da PA (MRPA) e a automedida da PA (AMPA)). A partir desses métodos, duas outras formas de classificação da PA foram incorporadas ao conhecimento: Hipertensão do Avental Branco (HAB) e Hipertensão Mascarada (HM)1 , 3 - 5 (Figura 1).

Classificação do comportamento da pressão arterial, considerando-se a PA de consultório, a MAPA e as medidas domiciliares da PA<sup>1</sup>. MAPA: Monitorização ambulatorial da pressão arterial; PA: Pressão arterial.

Os estudos epidemiológicos e clínicos acerca dessas condições são ainda limitados; entretanto, elas merecem atenção pelo maior risco CV a elas relacionado, quando comparadas à normotensão6 , 7.

Por essas razões, este documento apresenta o posicionamento do Departamento de Hipertensão Arterial da Sociedade Brasileira de Cardiologia (DHA/SBC) sobre o diagnóstico e a abordagem terapêutica não medicamentosa e medicamentosa de PH, HAB e HM, com o objetivo de contribuir para uma melhor prática clínica ante essas condições.

 Pré-hipertensão Epidemiologia

O termo PH foi descrito em 2003 na Diretriz Americana de Hipertensão Arterial1 que enfatizou a importância de medidas preventivas rigorosas ante esse comportamento de PA, considerando que pessoas com essas características apresentam maior incidência de HAS nos anos subsequentes e têm maior risco CV que aqueles com PA ótima (menor que 120/80 mmHg)2 , 3. Estudo demonstrou que nos pré-hipertensos, na faixa etária de 40-49 anos, a incidência de hipertensão nos próximos dez anos é de 80%8.

No estudo epidemiológico PURE, que avaliou 153.996 indivíduos em 17 países, a prevalência de PH foi de 36,8%, maior inclusive que a taxa de HAS, que foi de 34,3%. Dados da população adulta americana apontam para uma prevalência de 40%9.

Sabe-se ainda que a pré-hipertensão está frequentemente associada a outros fatores de risco CV, tais como obesidade, resistência a insulina, diabete melito, dislipidemia e outros fenótipos da síndrome metabólica, resultando em anormalidades vasculares precoces e progressão para a aterosclerose10.

 Diagnóstico e estratégias clínicas de identificação

Define-se PH quando a PA de consultório encontra-se entre 120 e 139 mmHg para a PAS e/ou entre 80 e 89 mmHg para a PAD2.A sua identificação depende da realização regular de medidas da PA, o que é recomendado pelo menos uma vez ao ano.

O diagnóstico da PH tem como base a medida de consultório da PA, mas, certamente, tal diagnóstico pode ser aprimorado com as medidas da MAPA 24h e/ou MRPA. Essas formas de avaliação da PA fora do consultório têm a vantagem de prover um número muito maior de medidas, fora dos ambientes em que a PA é usualmente medida, o que representa um registro mais fiel do comportamento da pressão arterial4 , 5. É importante identificar a presença de HM entre os pré-hipertensos.

Existem evidências de que o aumento da Massa Ventricular Esquerda (MVE) em pré-hipertensos seja um forte preditor de HAS em quatro anos, independentemente de outros fatores metabólicos e antropométricos associados. O aumento da MVE está possivelmente associado com uma maior carga hemodinâmica diária que poderia não ser detectada pelas medidas da PA no consultório. Variabilidade aumentada da pressão, ausência de queda durante o sono ou exposição sustentada e prolongada a pressões arteriais mais elevadas durante as atividades na vigília poderiam explicar os valores maiores da MVE nos indivíduos com PH. Além disso, a progressão de PH para a hipertensão tem sido associada com rigidez arterial aumentada11 , 12.

 Valor prognóstico

A PH é uma condição precursora da HAS, associa-se a outros fatores de risco CV e apresenta maior morbidade e mortalidade por causas CV6 , 13.

Na população avaliada no estudo de Framingham, o desenvolvimento de HAS em indivíduos abaixo dos 65 anos, em quatro anos de seguimento, ocorreu em percentuais diferentes nos três estratos de PA considerados normais: 5,3% dos indivíduos com pressão ótima; 17,6% naqueles com pressão normal; e 37,3% nos considerados com pressão normal alta à época. Nos indivíduos com mais de 65 anos essas taxas corresponderam a 16%, 25,5% e 49,5%, respectivamente14.Dados obtidos de dois estudos British Health and Lifestyle Surveys conduzidos com sete anos de diferença entre si utilizaram um subgrupo de 2.048 pacientes normotensos, demonstrando também um maior risco de desenvolvimento de HAS entre aqueles com PA mais elevada, especialmente nos mais jovens15. Outros estudos encontraram uma taxa de progressão para hipertensão arterial, em três anos, nos indivíduos acima dos 45 anos de 56,4%, (56,9% para homens e 55,9% para mulheres)16.

No Brasil, em um estudo de base populacional, quatro em cinco indivíduos pré-hipertensos com idade entre 40-49 anos desenvolveram HAS em 10 anos8.

Em relação ao risco aumentado de eventos CV em pacientes com PH, vale a pena mencionar dados de estudos longitudinais do Framingham Heart Study indicando que valores de PAS entre 130-139 e PAD de 85-89 mmHg estão associados com um aumento cerca de duas vezes maior de risco de doenças CV (DCV) quando comparados com valores de 120/80 mmHg14. Essa associação mostrou-se mais significativa nos indivíduos diabéticos e naqueles com índice de massa corporal (IMC) mais elevado17. Indivíduos com PH são mais propensos a sofrer um Infarto Agudo do Miocárdio (IAM) ou terem Doença Arterial Coronariana (DAC) do que aqueles considerados normotensos18. Um estudo japonês encontrou uma elevação de 45% no risco de eventos CV no grupo de pacientes pré-hipertensos quando comparados aos indivíduos normotensos, após ajuste de todos os outros fatores de risco tradicionais19.

 Hipertensão do avental branco Epidemiologia

A prevalência da HAB é muito variável em razão de os critérios para o diagnóstico serem diversos, envolvendo não só os aspectos relacionados à medida da PA, como também às populações estudadas. A prevalência global da HAB, baseada em quatro estudos populacionais é, em média, 13%, e atingiu cerca de 32% entre hipertensos nessas pesquisas20. De maneira geral, os valores na população giram em torno de 10% a 20%, sendo mais comum em crianças e idosos, no sexo feminino e em não fumantes21 , 22.

A prevalência também está relacionada com a PA do consultório, sendo o percentual de HAB equivalente a 55% em hipertensos estágio 1, e apenas 10% na hipertensão estágio 321. Entretanto, em indivíduos onde a PAD de consultório for superior a 105 mmHg, a HAB é um achado improvável23. Esse fenômeno ocorre também em hipertensos tratados e é chamado de efeito do avental branco. Muxfeldt e cols.24 avaliaram pacientes hipertensos não controlados em tratamento anti-hipertensivo, onde mais de 60% estavam com três ou mais fármacos e 37% apresentavam o efeito do avental branco. No estudo PAMELA (Pressione Arteriose Monitorate E Lara Associazioni), em seguimento de dez anos, nos pacientes com síndrome metabólica que apresentavam HAB à primeira consulta, verificou-se que 42,6% deles desenvolveram hipertensão arterial sustentada25.

A HAB é mais prevalente quanto maior o IMC. Helvaci e cols.26, estudando o comportamento da pressão arterial em indivíduos avaliados em clínicas de check-up, encontraram a prevalência de HAB de 19,6% nos indivíduos com IMC inferior a 18,5 kg/m2, no grupo com IMC entre 18,5 a 24,9 kg/m2, os valores foram de 35,6% e naqueles com sobrepeso (IMC entre 25 e 29,9 kg/m2), a prevalência foi de 68,4%26.

A HAB aumenta com a idade e, de uma forma geral, em indivíduos maiores de 65 anos, a prevalência gira entre 43% e 45%27.

Em um período de até 6,5 anos de seguimento, Verdecchia e cols.28 observaram que o risco de desenvolver hipertensão arterial foi de 37% nos indivíduos com HAB. Essa probabilidade se relacionou com os valores basais da MAPA e não com a pressão de consultório.

 Diagnóstico e estratégias clínicas de identificação

Para o diagnóstico da HAB se faz necessária a realização de medidas da PA no consultório e fora dele, seja por MAPA, seja por medidas domiciliares4. Recomenda-se que sejam seguidos os limites adotados nas diretrizes mais recentes do NICE29, da ESH/ESC 20133 e do ESH Position Paper on Ambulatory Blood Pressure Monitoring5 que mantêm os valores do JNC 72 e ESH/ESC 2003 e 200730 , 31, e foram baseados em estudos como IDACO32 e Ohasama33 (Tabela 1).

Limites de anormalidade para diagnóstico de hipertensão por MAPA 24h e medidas domiciliares da PA
Medidas fora do consultório PAS e/ou PAD (mmHg)
MAPA
Média de 24h ≥ 130/80
Média de Vigília ≥ 135/85
Média de Sono ≥ 120/70
Medida Domiciliar ≥ 135/85

MAPA: Monitorização ambulatorial da pressão arterial; PAS: Pressão arterial sistólica; PAD: Pressão arterial diastólica.

Caracteriza-se a HAB quando os valores da medida da PA no consultório ≥ 140 mmHg para a PAS e/ou ≥ 90 mmHg para a PAD, e valores considerados normais de pressão arterial fora do consultório, < 135/85 mmHg, nas medidas realizadas na MAPA durante o período de vigília ou nas medidas domiciliares (MRPA ou AMPA), conforme demonstrado na tabela 1 e nas figuras 1 e 2. O posicionamento da Sociedade Europeia de Hipertensão para MAPA recomenda que as médias da PA nas 24h e da PA noturna também devem ser normais para o diagnóstico de HAB5.

Representação esquemática do comportamento da PA no consultório e na MAPA ou medidas domiciliares da PA para o diagnóstico de hipertensão do avental branco. PAS: Pressão arterial sistólica; PAD: Pressão arterial diastólica; MAPA: Monitorização ambulatorial da pressão arterial; MRPA: Monitorização residencial da PA; AMPA: Automedida da PA.

Nessa condição, ocorre mudança de diagnóstico de hipertensão arterial no consultório para HAB. Recomenda-se que em indivíduos com hipertensão de consultório nos estágios 1 e 2, sem outras comorbidades ou lesão em órgãos-alvo, deve-se complementar a avaliação com a obtenção de medidas fora do consultório (figura 3).

Fluxograma para identificação da hipertensão do avental branco. MAPA: Monitorização ambulatorial da pressão arterial; MRPA: Monitorização residencial da PA; AMPA: Automedida da PA.

O efeito do avental branco é definido como o valor ≥ 20 e 10 mmHg, respectivamente, nas PAS e PAD34 entre a medida da PA no consultório e a média da MAPA na vigília ou das medidas domiciliares, sem que haja mudança no diagnóstico de normotensão ou hipertensão.

O emprego do termo medidas domiciliares deve prosperar em substituição aos termos para denominar os métodos MRPA e AMPA. Assim, a realização da AMPA deve ser estimulada com o emprego de equipamentos também validados, com manguitos aplicáveis ao braço e cuja calibração seja testada periodicamente. A principal diferença para a MRPA é o uso de um protocolo determinado neste último, caracterizando que ambos os métodos possuem mais semelhanças que diferenças e podem ser tratados em conjunto35.

 Valor prognóstico

Desfechos CV relacionados à HAB ainda despertam inúmeras controvérsias. Estudos sugerem que a HAB apresenta risco mais baixo, semelhante ao de normotensos, com tendência de aumento do risco em longo prazo.Meta-análise realizada com 7.030 indivíduos evidencia a existência de risco cardiovascular crescente a partir da normotensão, seguindo-se HAB, HM e, por fim, hipertensão20 , 36 - 39.

Com relação ao risco de desenvolvimento de hipertensão, o estudo PAMELA demonstrou que, após dez anos, os indivíduos previamente diagnosticados com HAB ou com HM se tornaram portadores de hipertensão sustentada numa proporção significativamente maior do que normotensos25.

 Hipertensão mascarada Epidemiologia

Denomina-se hipertensão mascarada a situação em que há normotensão nas medidas de PA realizadas no consultório com valores anormais nas medidas fora dele, por medidas ambulatoriais ou domiciliares da PA (MAPA, MRPA ou AMPA)40.

A HM tem uma prevalência estimada entre 8% e 20%, em adultos sem tratamento, e de 50% ou mais nos indivíduos em uso de medicamentos41. Uma meta-análise, envolvendo 28 estudos, estimou a prevalência de HM em 16,8% na população geral. Entre crianças, a prevalência estimada é de 7%42. Maior prevalência de HM foi observada quando a PA de consultório está na faixa normal alta41. A PA dentro de faixas normais no consultório em comparação a valores ambulatoriais anormais tem sido atribuída, entre outros fatores, ao fenômeno de "regressão à média"40. Outros fatores também têm se correlacionado com a HM30 , 40 , 43 - 48, conforme demonstrado no quadro 1. Em um estudo envolvendo 3.400 pacientes hipertensos tratados, os principais fatores associados à HM foram sobrepeso (1,38, IC 95%, 1,09-1,75) e consumo regular de álcool (OR, 1,37; IC 95%, 1,09-1,72)42. Em um outro estudo, o risco de HM foi maior nos homens do que nas mulheres (RR, 1,14, IC 95%, 1,01-1,28) e em fumantes (RR, 1,16; IC 95%, 1,04-1,30)49. Outra publicação demonstrou que as mulheres eram menos propensas que os homens a ter HM (OR, 0,39, IC 95%, 0,22- 0,68)47

Fatores relacionados à presença de hipertensão mascarada<xref ref-type="bibr" rid="B02">2</xref> <sup>,</sup> <xref ref-type="bibr" rid="B04">4</xref> <sup>-</sup> <xref ref-type="bibr" rid="B11">11</xref>
Sexo masculino
Idade jovem
História familiar para hipertensão arterial
Tabagismo
Consumo de álcool
Atividade física aumentada
Hipertensão induzida pelo esforço
Medidas de PA ocasionalmente elevadas
Obesidade
Diabetes
Doença renal crônica
Hipertrofia ventricular esquerda
Múltiplos fatores de risco associados
Apneia do sono
Fatores psicossociais: ansiedade, conflitos interpessoais, estresse no trabalho

Classicamente, caracteriza-se a presença de HM em indivíduos não tratados. Recentemente, a literatura tem chamado a atenção para a ocorrência de PA normal no consultório e elevada fora dele em indivíduos tratados. Níveis mais baixos de ansiedade e a utilização de medicação anti-hipertensiva apenas antes da consulta médica, com o pico de ação do fármaco no momento do exame, também têm sido listados como fatores causais nessa situação44 , 46 , 50.

 Diagnóstico e estratégias clínicas de identificação

Hipertensão Mascarada refere-se a pacientes não tratados, nos quais as medidas de consultório estão sistematicamente normais, PA < 140/90 mmHg, com elevação na MAPA ou medidas domiciliares - média PA vigília ou média de PA domiciliar ≥ 135/85 mmHg51 , 52 (tabela 1 e figuras 1 e 4). Destaca-se que o posicionamento da Sociedade Europeia de Hipertensão para MAPA considerou também as médias da PA de 24h e da PA noturna elevadas como critérios para o diagnóstico de HM, mesmo que a média da PA de vigília seja normal5.

Representação esquemática do comportamento da PA no consultório e na MAPA ou medidas domiciliares da PA para o diagnóstico de hipertensão mascarada. PAS: Pressão arterial sistólica; PAD: Pressão arterial diastólica; MAPA: Monitorização ambulatorial da pressão arterial; MRPA: Monitorização residencial da PA; AMPA: Automedida da PA.

As condições expostas no quadro 1 estão relacionadas à HM, e quando presentes, o diagnóstico pode ser suspeitado e a MAPA deverá ser considerada para se obter mais adequada análise do real comportamento da PA. Especialmente, a presença de lesões em órgãos-alvo e o relato de repetidas medidas elevadas da PA fora do consultório devem fazer suspeitar de HM1 , 3 - 5 , 48 , 53 , 54.

A identificação da HM também poderá ser feita com base em repetidas medidas da PA durante os períodos da manhã e tarde com adequadas sensibilidade e especificidade7. Entretanto, a reprodutibilidade em longo prazo das medidas dessa forma realizadas tem sido questionada por vários autores55.

 Valor prognóstico

O valor prognóstico da HM é controverso, havendo trabalhos comprovando o maior risco CV, enquanto outros não demonstram tal relação. Vários autores observaram que, em hipertensos, a MAPA e a medida domiciliar são superiores à medida da PA no consultório como preditores independentes, tanto de lesões em órgãos-alvo56 , 57 como do risco cardiovascular58.Por outro lado, Cuspidi e cols.59 realizaram uma análise de 13 estudos buscando relacionar a HM com a Hipertrofia Ventricular Esquerda (HVE). Os autores concluíram que a relação entre HM e o desenvolvimento de HVE foi limitada59.

Por outro lado, o remodelamento concêntrico e a HVE, o espessamento de camada íntima média e a presença de placas ateroscleróticas de carótidas e a microalbuminúria foram achados mais prevalentes na HM do que na população de normotenso56.

Hanninen e cols.60 investigaram o valor prognóstico da HM em uma amostra da população geral na Finlândia. Foram incluídos 2.046 indivíduos normotensos e hipertensos com diferentes fatores de risco CV associados. Os autores concluíram que, avaliando-se o risco CV pela medida da PA domiciliar, pacientes com HM apresentam risco CV ajustado para a idade maior que normotensos. Entretanto, a HM não foi um preditor de risco CV independente quando a medida basal domiciliar da PA foi ajustada para outros fatores de risco tradicionais. Eles concluíram, então, que valores de pressão domiciliar associados a outros fatores de risco tradicionais são suficientes para estratificação do risco CV.

Meta-análises de estudos prospectivos indicaram um risco de eventos CV duas vezes maior na HM que na normotensão verdadeira, incidência semelhante à observada na HAS verdadeira. Possivelmente, a não detecção da HM e a consequente ausência de tratamento devam ter contribuído para esse resultado20 , 37 , 41.

 Tratamento não medicamentoso da pré-hipertensão, hipertensão do avental branco e hipertensão mascarada: eficácia e dificuldades para a sua implementação

Não há dúvidas quanto aos benefícios obtidos com Mudanças no Estilo de Vida (MEV) nos portadores de HAS, nos pré-hipertensos, e há boas indicações de que esses se estendem aos com HAB e aqueles com HM1 , 3.

As principais MEV com essa finalidade são: controle do peso, mudança alimentar com adoção da dieta DASH (rica em frutas, hortaliças, fibras, minerais e laticínios com baixos teores de gorduras), diminuição no consumo de sal, redução no consumo de álcool, cessação do tabagismo, incentivo à prática de atividade física, além do controle do estresse psicossocial1 , 3.

Inúmeros estudos clínicos que avaliaram essas medidas mostraram redução significativa na PA entre os hipertensos e pré-hipertensos e postergaram o aparecimento da HAS neste último grupo61 - 68.

Com relação à HAB, o incentivo às MEV está embasado em algumas razões: a HAB não é inócua, visto que seus portadores podem apresentar alterações em órgãos-alvo; as MEV devem ser a estratégia inicial para redução da PA, em qualquer tipo de alteração do comportamento da PA; são recomendadas como importante estratégia para prevenir ou retardar o surgimento de HAS na população geral; portadores de HAB têm maior probabilidade de desenvolver HAS sustentada; apresentam benefícios claros para os outros fatores de risco CV; o tratamento medicamentoso da HAB ainda é controverso1 , 3 , 20.

Na hipertensão mascarada, as recomendações poderão ser mais específicas de acordo com o período do dia em que ocorre a elevação da pressão arterial, tais como hipertensão matutina, diurna e noturna69.

Para a hipertensão matutina é recomendada redução da ingestão de álcool e do estresse físico e mental70. Na hipertensão na vigília o abandono do tabagismo é imprescindível, assim como o controle do estresse físico e mental71. Para os que apresentam hipertensão durante o sono recomenda-se a restrição de sal, já que é observada com maior frequência nos indivíduos sal-sensíveis72, e redução do peso, especialmente para os obesos com síndrome da apneia obstrutiva do sono73.

Além do acompanhamento de perto pelo profissional médico, a equipe multiprofissional desempenha um papel fundamental nessa abordagem, motivando a adesão e buscando garantir que as mudanças sejam permanentes1 , 3 , 74 - 76.

Apesar das evidências, a grande limitação e motivo de desconfiança é a efetividade dessas medidas que envolvem MEV fora do contexto dos ensaios clínicos. Na vida real, mesmo os mais motivados encontram dificuldades em sustentar MEV, pressionados pelas forças culturais, hábitos arraigados em anos de vida, normas da sociedade e interesses comerciais que incentivam o sedentarismo, a dieta inadequada e o consumo exagerado de calorias77. Esse fato acaba por criar expectativas pelas possibilidades de alternativas medicamentosas para o enfrentamento dessas situações78 , 79.

 Tratamento medicamentoso Pré-hipertensão

A PH representa estágio intermediário para a HAS estabelecida e a sua conversão em hipertensão arterial sustentada é mais acelerada em negros8 , 80. O Sistema Renina-Angiotensina-Aldosterona (SRAA) está frequentemente ativado em indivíduos pré-hipertensos81. Essas evidências sugerem que a intervenção precoce com medicamentos pode reduzir a incidência de hipertensão sustentada e evitar a progressão da DCV.

Os estudos TROPHY13 e PHARAO82 foram os primeiros a demonstrar que inibidores do SRAA reduzem a incidência de hipertensão. O TROPHY avaliou 772 indivíduos com PA de 130-139/85-89 mmHg, randomizados para receberem placebo ou candesartana (16 mg/dia - grupo intervenção). Todos receberam orientações quanto a MEV. Após quatro anos, observou-se menor incidência de HAS (9,8%) no grupo intervenção, com redução do Risco Relativo (RR) de 16% e Número Necessário para Tratar (NNT) de 1113. Esse estudo foi questionado em alguns aspectos metodológicos, que podem ter sobrevalorizado os seus resultados. O PHARAO avaliou 1.008 pré-hipertensos com PA de 130-139/85-89 mmHg, durante três anos, que foram aleatoriamente alocados para receber ramipril 5 mg/dia ou placebo. No grupo ramipril observou-se redução do RR de 34% na incidência de HAS avaliada pela PA de consultório (NNT = 9) e MAPA (32,5% vs. 53,0), com aumento da incidência de tosse (4,8 vs. 0,4%)82. No entanto, se esses benefícios permanecem em longo prazo, se previnem eventos CV e se são custo-efetivos, são informações que permanecem ainda não esclarecidas.

As diretrizes atuais recomendam MEV a todos pré-hipertensos, e intervenção com medicamentos somente nos indivíduos com PA na faixa normal alta de alto risco, com DCV ou doença renal estabelecida, síndrome metabólica ou diabetes1, a critério da decisão médica individualizada. Destaca-se que até o momento só há evidências para o uso de bloqueadores do SRAA. Vale ressaltar que as recentes diretrizes europeias de hipertensão destacaram a ausência de evidências científicas suficientes que suportem a recomendação de início de tratamento medicamentoso na faixa de PA normal alta.

Em face das evidências comentadas e da baixa efetividade da MEV em longo prazo, propõe-se que a decisão de utilizar doses baixas de anti-hipertensivos em indivíduos com pré-hipertensão e sem DCV, mas sob alto risco de desenvolver hipertensão arterial sustentada, possa ser considerada83 - 85.

 Hipertensão do Avental Branco (HAB)

O benefício do tratamento medicamentoso para a HAB permanece indefinido, porque a questão nunca foi avaliada em um ensaio clínico especificamente desenhado para testar essa hipótese. Além disso, grandes estudos clínicos desenhados para mostrar proteção em órgãos-alvo com tratamento anti-hipertensivo nunca usaram MAPA ou medidas domiciliares da PA, exceto em pequenos subgrupos, com pequeno número de eventos CV, que não permitiram conclusões definitivas.

Na ausência de evidências diretas, recomenda-se que na presença de alto ou muito alto risco CV (concomitância de DCV ou doença renal, lesões em órgãos-alvo, síndrome metabólica ou diabetes), o tratamento anti-hipertensivo na HAB pode ser considerado. Portanto, a avaliação dos fatores de risco CV e determinação do risco em indivíduos com HAB são essenciais para a tomada de decisão individualizada sobre o tratamento anti-hipertensivo86.

Recomenda-se que o seguimento desses pacientes seja feito com MAPA ou medidas domiciliares da PA

 Hipertensão Mascarada (HM)

Há significativa base científica do impacto negativo da HM na morbidade e na mortalidade CV que justificam identificar e tratar esses pacientes de forma similar aos pacientes hipertensos de consultório42.

Até o momento não foram realizados estudos clínicos em pacientes com HM, que demonstrem a relação entre a queda da PA e a redução do risco CV. A consideração de início de tratamento medicamentoso para pacientes com HM baseia-se no fato de que esses indivíduos são reais hipertensos fora do consultório, com risco CV semelhante aos hipertensos não tratados50 , 87.

Os pacientes com HM devem ser estratificados e tratados da mesma forma que os hipertensos convencionais50. Sugere-se que a eficácia do tratamento anti-hipertensivo seja avaliada por medidas de PA obtidas fora do consultório.

Vinculação Acadêmica

Não há vinculação desse estudo a programas de pós-graduação.

Fontes de Financiamento

O presente estudo não teve fontes de financiamento externas

 Referências 1. Sociedade Brasileira de Cardiologia. Sociedade Brasileira de Nefrologia. Sociedade Brasileira de Hipertensão. VI Diretrizes Brasileiras de Hipertensão. Arq Bras Cardiol. 2010;95(1 supl 1):1-51. Sociedade Brasileira de Cardiologia Sociedade Brasileira de Nefrologia Sociedade Brasileira de Hipertensão VI Diretrizes Brasileiras de Hipertensão Arq Bras Cardiol 2010 95 1 supl 1 1 51 2. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, et al. The National High Blood Pressure Education Program Coordinating Committee. Seventh Report os the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension. 2003;42(6):1206-52. Chobanian AV Bakris GL Black HR Cushman WC Green LA Izzo JL Jr et al The National High Blood Pressure Education Program Coordinating Committee. Seventh Report os the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure Hypertension 2003 42 6 1206 1252 3. Mancia G, Fagard R, Narkiewicz K, Rédon J, Zanchetti A, Böhm M, et al; Task Force Members. 2013 ESH/ESC Guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens. 2013;31(7):1281-357. Mancia G Fagard R Narkiewicz K Rédon J Zanchetti A Böhm M et al Task Force Members 2013 ESH/ESC Guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC) J Hypertens 2013 31 7 1281 1357 4. Sociedade Brasileira de Cardiologia, Sociedade Brasileira de Hipertensão, Sociedade Brasileira de Nefrologia. V Diretrizes Brasileiras de Monitorização Ambulatorial da Pressão Arterial (MAPA) e III Diretrizes Brasileiras de Monitorização Residencial de Pressão Arterial (MRPA). Arq Bras Cardiol. 2011;97 (3 supl.3):1-24. Sociedade Brasileira de Cardiologia Sociedade Brasileira de Hipertensão Sociedade Brasileira de Nefrologia V Diretrizes Brasileiras de Monitorização Ambulatorial da Pressão Arterial (MAPA) e III Diretrizes Brasileiras de Monitorização Residencial de Pressão Arterial (MRPA) Arq Bras Cardiol 2011 97 3 supl.3 1 24 5. O'Brien E, Parati G, Stergiou G, Asmar R, Beilin L, Bilo G, et al; European Society of Hypertension Working Group on Blood Pressure Monitoring. European Society of Hypertension position paper on ambulatory blood pressure monitoring. J Hypertens. 2013;31(9):1731-68. Erratum in J Hypertens. 2013;31(12):2467. O'Brien E Parati G Stergiou G Asmar R Beilin L Bilo G et al European Society of Hypertension Working Group on Blood Pressure Monitoring European Society of Hypertension position paper on ambulatory blood pressure monitoring J Hypertens 2013 31 9 1731 1768 Erratum in J Hypertens. 2013;31(12):2467 6. Vasan RS, Larson MG, Leip EP, Evans JC, O´Donnel CJ, Kannel WB, et al. Impact of high-normal blood pressure on the risk of cardiovascular disease. N Engl J Med. 2001;345(18):1291-7. Vasan RS Larson MG Leip EP Evans JC O´Donnel CJ Kannel WB et al Impact of high-normal blood pressure on the risk of cardiovascular disease N Engl J Med 2001 345 18 1291 1297 7. Conen D, Ricker PM, Buring JE, Glynn RJ. Risk of cardiovascular events among women with high normal blood pressure or blood pressure progression: prospective cohort study. BMJ. 2007;335(7617):432-40. Conen D Ricker PM Buring JE Glynn RJ Risk of cardiovascular events among women with high normal blood pressure or blood pressure progression: prospective cohort study BMJ 2007 335 7617 432 440 8. Moreira LB, Fuchs SC, Wiehe M, Gus M, Moraes RS, Fuchs FD. Incidence of hypertension in Porto Alegre, Brazil: a population-based study. J Hum Hypertens. 2008;22(1):48-50. Moreira LB Fuchs SC Wiehe M Gus M Moraes RS Fuchs FD Incidence of hypertension in Porto Alegre, Brazil: a population-based study J Hum Hypertens 2008 22 1 48 50 9. Lloyd-Jones D, Adams R, Carnethon M, De Simone G, Ferguson B, Flegal K, et al; American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics - 2009 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation. 2009;119(3):e21-181. Lloyd-Jones D Adams R Carnethon M De Simone G Ferguson B Flegal K et al American Heart Association Statistics Committee and Stroke Statistics Subcommittee Heart disease and stroke statistics - 2009 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee Circulation 2009 119 3 e21 181 10. De Marco M, de Simone G, Roman MJ, Chinalli M, Lee ET, Russel M, et al. Cardiovascular and metabolic predictors of progression of prehypertension into hypertension: the Strong Heart Study. Hypertension. 2009;54(5):974-80. De Marco M de Simone G Roman MJ Chinalli M Lee ET Russel M et al Cardiovascular and metabolic predictors of progression of prehypertension into hypertension: the Strong Heart Study Hypertension 2009 54 5 974 980 11. Safar ME, Frohlich ED. (eds): Atherosclerosis, large arteries and cardiovascular risk. Adv Cardiol. Basel: Karger; 2007. p. 117-24. Safar ME Frohlich ED Atherosclerosis, large arteries and cardiovascular risk Adv Cardiol. Basel: Karger 2007 117 124 12. Kaess BM, Rong J, Larson MG, Hamburg NM, Vita JA, Levy D, et al. Aortic stiffness, blood pressure progression, and incident hypertension. JAMA. 2012;308(9):875-81. Kaess BM Rong J Larson MG Hamburg NM Vita JA Levy D et al Aortic stiffness, blood pressure progression, and incident hypertension JAMA 2012 308 9 875 881 13. Julius S, Nesbitt SD, Egan BM, Weber MA, Michelson EL, Kaciroti N, et al; Trial of Preventing Hypertension (TROPHY) Study Investigators. Feasibility of treating prehypertension with an angiotensin-receptor blocker. N Engl J Med. 2006;354(16):1685-97. Julius S Nesbitt SD Egan BM Weber MA Michelson EL Kaciroti N et al Trial of Preventing Hypertension (TROPHY) Study Investigators Feasibility of treating prehypertension with an angiotensin-receptor blocker N Engl J Med 2006 354 16 1685 1697 14. Vasan RS, Larson MG, Leip EP, Kannel WB, Levy D. Assessment of frequency of progression to hypertension in non-hypertensive participants in the Framingham Heart Study: a cohort study. Lancet. 2001;358(9294):1682-6. Vasan RS Larson MG Leip EP Kannel WB Levy D Assessment of frequency of progression to hypertension in non-hypertensive participants in the Framingham Heart Study: a cohort study Lancet 2001 358 9294 1682 1686 15. Winegarden CR. From "prehypertension" to hypertension?: additional evidence. Ann Epidemiol. 2005;15(9):720-5. Winegarden CR From "prehypertension" to hypertension: additional evidence Ann Epidemiol 2005 15 9 720 725 16. Kim YM, Hong KS, Choi YH, Choi MG, Jeong JY, Lee JM, et al. Rates and related factors of progression to hypertension among prehypertensive local residents aged 45 or over in Chuncheon City: hallym aging study from a community-based cross-sectional study. Korean Circ J. 2008;38(1):43-50. Kim YM Hong KS Choi YH Choi MG Jeong JY Lee JM et al Rates and related factors of progression to hypertension among prehypertensive local residents aged 45 or over in Chuncheon City: hallym aging study from a community-based cross-sectional study Korean Circ J 2008 38 1 43 50 17. Kshirsagar AV, Carpenter M, Bang H, Wyatt SB, Colindres RE. Blood pressure usually considered normal is associated with an elevated risk of cardiovascular disease. Am J Med. 2006;119(2):133-41. Kshirsagar AV Carpenter M Bang H Wyatt SB Colindres RE Blood pressure usually considered normal is associated with an elevated risk of cardiovascular disease Am J Med 2006 119 2 133 141 18. Qureshi AI, Suri MF, Kirmani JF, Divani AA, Mohammad Y. Is prehypertension a risk factor for cardiovascular diseases? Stroke. 2005;36(9):1859-63. Qureshi AI Suri MF Kirmani JF Divani AA Mohammad Y Is prehypertension a risk factor for cardiovascular diseases? Stroke 2005 36 9 1859 1863 19. Ishikawa Y, Ishikawa J, Ishikawa S, Kayaba K, Nakamura Y, Shimada K, et al., Prevalence and determinants of prehypertension in a Japanese general population: the Jichi Medical School Cohort Study. Hypertens Res. 2008;31(7):1323-30. Ishikawa Y Ishikawa J Ishikawa S Kayaba K Nakamura Y Shimada K et al Prevalence and determinants of prehypertension in a Japanese general population: the Jichi Medical School Cohort Study Hypertens Res 2008 31 7 1323 1330 20. Fagard RH, Cornelissen VA. Incidence of cardiovascular events in white-coat, masked and sustained hypertension vs. true normotension: a meta-analysis. J Hypertens. 2007;25(11):2193-8. Fagard RH Cornelissen VA Incidence of cardiovascular events in white-coat, masked and sustained hypertension vs. true normotension: a meta-analysis J Hypertens 2007 25 11 2193 2198 21. Staessen JA, O'Brien ET, Amery AK, Atkins N, Baumgart P, De Cort P, et al. Ambulatory blood pressure in normotensive and hypertensive subjects: results from an international database. J Hypertens Suppl. 1994;12(7):S1-12. Staessen JA et al O'Brien ET Amery AK Atkins N Baumgart P De Cort P Ambulatory blood pressure in normotensive and hypertensive subjects: results from an international database J Hypertens Suppl 1994 12 7 S1 12 22. Dolan E, Stanton A, Atkins N, Den Hond E, Thijs L, McCormack P, et al. Determinants of white-coat hypertension. Blood Press Monit. 2004;9(6):307-9. Dolan E Stanton A Atkins N Den Hond E Thijs L McCormack P et al Determinants of white-coat hypertension Blood Press Monit 2004 9 6 307 309 23. Angeli F, Verdecchia P, Gattobigio R, Sardone M, Reboldi G. White-coat hypertension in adults. Blood Press Monit. 2005;10(6):301-5. Angeli F Verdecchia P Gattobigio R Sardone M Reboldi G White-coat hypertension in adults Blood Press Monit 2005 10 6 301 305 24. Muxfeldt ES, Bloch KV, Nogueira AR, Salles GF True resistant hypertension: is it possible to be recognized in the office? Am J Hypertens. 2005;18(12 Pt 1):1534-40. Muxfeldt ES Bloch KV Nogueira AR Salles GF True resistant hypertension: is it possible to be recognized in the office? Am J Hypertens 2005 18 12 Pt 1 1534 1540 25. Mancia G, Bombelli M, Facchetti R, Madotto F, Quarti-Trevano F, Polo Friz H, et al. Long-term risk of sustained hypertension in white-coat or masked hypertension. Hypertension. 2009;54(2):226-32. Mancia G Bombelli M Facchetti R Madotto F Quarti-Trevano F Polo Friz H et al Long-term risk of sustained hypertension in white-coat or masked hypertension Hypertension 2009 54 2 226 232 26. Helvaci MR, Kaya H, Yalcin A, Kuvandik G. Prevalence of white coat hypertension in underweight and overweight subjects. Int Heart J. 2007;48(5):605-13. Helvaci MR Kaya H Yalcin A Kuvandik G Prevalence of white coat hypertension in underweight and overweight subjects Int Heart J 2007 48 5 605 613 27. Pickering TG, James GD, Boddie C, Harshfield GA, Blank S, Laragh JH. How common is white coat hypertension? JAMA. 1988;259(2):225-8. Pickering TG James GD Boddie C Harshfield GA Blank S Laragh JH How common is white coat hypertension? JAMA 1988 259 2 225 228 28. Verdecchia P, Palatini P, Schillaci G, Mormino P, Porcellati C, Pessina AC. Independent predictors of isolated clinic ('white-coat') hypertension. J Hypertens. 2001;19(6):1015-20. Verdecchia P Palatini P Schillaci G Mormino P Porcellati C Pessina AC Independent predictors of isolated clinic ('white-coat') hypertension J Hypertens 2001 19 6 1015 1020 29. National Institute for Health and Clinical Excellence (NICE). Hypertension: the clinical management of primary hypertension in adults. Clinical Guideline CG 127; August 2011. National Institute for Health and Clinical Excellence (NICE) Hypertension: the clinical management of primary hypertension in adults Clinical Guideline CG 127 August 2011 30. O'Brien E, Asmar R, Beilin L, Imai Y, Mallion JM, Mancia G, et al; European Society of Hypertension Working Group on Blood Pressure Monitoring. European Society of Hypertension recommendations for conventional, ambulatory and home blood pressure measurement. J Hypertens. 2003;21(5):821-48. O'Brien E Asmar R Beilin L Imai Y Mallion JM Mancia G et al European Society of Hypertension Working Group on Blood Pressure Monitoring European Society of Hypertension recommendations for conventional, ambulatory and home blood pressure measurement J Hypertens 2003 21 5 821 848 31. Mancia G, De Backer G, Dominiczak A, Cifkova R, Fagard R, Germano G, et al; Management of Arterial Hypertension of the European Society of Hypertension; European Society of Cardiology. 2007 Guidelines for the Management of Arterial Hypertension: the Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens. 2007;25(6):1105-87. Erratum in: J Hypertens. 2007;25(8):1749. Mancia G De Backer G Dominiczak A Cifkova R Fagard R Germano G et al Management of Arterial Hypertension of the European Society of Hypertension European Society of Cardiology 2007 Guidelines for the Management of Arterial Hypertension: the Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC) J Hypertens 2007 25 6 1105 1187 Erratum in: J Hypertens. 2007;25(8):1749. 32. Kikuya M, Hansen TW, Thijs L, Bjorklund-Bodegrd K, Kuznetsova T, Ohkubo T, et al; International Database on Ambulatory Blood Pressure monitoring in relation to Cardiovascular Outcomes Investigators. Diagnostic thresholds for ambulatory blood pressure monitoring based on 10-year cardiovascular risk. Circulation. 2007;115(16):2145-52. Kikuya M Hansen TW Thijs L Bjorklund-Bodegrd K Kuznetsova T Ohkubo T et al International Database on Ambulatory Blood Pressure monitoring in relation to Cardiovascular Outcomes Investigators Diagnostic thresholds for ambulatory blood pressure monitoring based on 10-year cardiovascular risk Circulation 2007 115 16 2145 2152 33. Ohkubo T, Imai Y, Tsuji I, Nagai K, Ito S, Satoh H, et al. Reference values for 24-h ambulatory blood pressure monitoring based on a prognostic criterion: the Ohasama study. Hypertension. 1998;32(2):255-9. Ohkubo T Imai Y Tsuji I Nagai K Ito S Satoh H et al Reference values for 24-h ambulatory blood pressure monitoring based on a prognostic criterion: the Ohasama study Hypertension 1998 32 2 255 259 34. Myers MG, Haynes RB, Rabkin SW. Canadian Hypertension Society guidelines for ambulatory blood pressure monitoring. Am J Hypertens. 1999;12(11 Pt 1):1149-57. Erratum in Am J Hypertens 2000;13(2):219. Myers MG Haynes RB Rabkin SW Canadian Hypertension Society guidelines for ambulatory blood pressure monitoring Am J Hypertens 1999 12 11 Pt 1 1149 1157 Erratum in Am J Hypertens 2000;13(2):219 35. Gomes MA, Paiva AM. MAPA e MRPA: o valor das medidas de pressão arterial fora do consultório. Revista Norte Nordeste de Cardiologia. 2013;3(2):10-20. Gomes MA Paiva AM MAPA e MRPA: o valor das medidas de pressão arterial fora do consultório Revista Norte Nordeste de Cardiologia 2013 3 2 10 20 36. Verdecchia P, Reboldi GP, Angeli F, Schillaci G, Schwartz JE, Pickering TG, et al. Short and long-term incidence of stroke in white coat hypertension. Hypertension. 2005;45(2):203-8. Verdecchia P Reboldi GP Angeli F Schillaci G Schwartz JE Pickering TG et al Short and long-term incidence of stroke in white coat hypertension Hypertension 2005 45 2 203 208 37. Pierdomenico SD, Cuccurullo F. Prognostic value of white-coat and masked hypertension diagnosed by ambulatory monitoring in initially untreated subjects: an update meta-analysis. Am J Hypertens. 2011;24(1):52-8. Pierdomenico SD Cuccurullo F Prognostic value of white-coat and masked hypertension diagnosed by ambulatory monitoring in initially untreated subjects: an update meta-analysis Am J Hypertens 2011 24 1 52 58 38. Franklin SS, Thijs L, Hansen TW, Li Y, Boggia J, Kikuya M, et al; International Database on Ambulatory Blood Pressure in Relation to Cardiovascular Outcomes Investigators. Significance of white-coat hypertension in older persons with isolated systolic hypertension: a meta-analysis using the International Database on Ambulatory Blood Pressure Monitoring in Relation to Cardiovascular Outcomes population. Hypertension. 2012;59(3):564-71. Franklin SS Thijs L Hansen TW Li Y Boggia J Kikuya M et al International Database on Ambulatory Blood Pressure in Relation to Cardiovascular Outcomes Investigators Significance of white-coat hypertension in older persons with isolated systolic hypertension: a meta-analysis using the International Database on Ambulatory Blood Pressure Monitoring in Relation to Cardiovascular Outcomes population Hypertension 2012 59 3 564 571 39. Hansen TW, Kikuya M, Thijs L, Bjorklund Bodegard K, Kuznetsova T, Ohkubo T, et al. Prognostic superiority of daytime ambulatory over conventional blood pressure in four populations: a meta-analysis of 7030 individuals. J Hypertens. 2007;25(8):1554-64. Hansen TW Kikuya M Thijs L Bjorklund Bodegard K Kuznetsova T Ohkubo T et al Prognostic superiority of daytime ambulatory over conventional blood pressure in four populations: a meta-analysis of 7030 individuals J Hypertens 2007 25 8 1554 1564 40. Pickering TG, Davidson K, Gerin W, Schwartz JE. Masked hypertension. Hypertension. 2002;40(6):795-6. Pickering TG Davidson K Gerin W Schwartz JE Masked hypertension Hypertension 2002 40 6 795 796 41. Bobrie G, Clerson P, Menard J, Postel-Vinay N, Chatellier G, Plouin PF. Masked hypertension: a systematic review. J Hypertens. 2008;26(9):1715-25. Bobrie G Clerson P Menard J Postel-Vinay N Chatellier G Plouin PF Masked hypertension: a systematic review J Hypertens 2008 26 9 1715 1725 42. Verberk WJ, Kessels AG, de Leeuw PW. Prevalence, causes, and consequences of masked hypertension: a meta-analysis. Am J Hypertens. 2008;21(9):969-75. Verberk WJ Kessels AG de Leeuw PW Prevalence, causes, and consequences of masked hypertension: a meta-analysis Am J Hypertens 2008 21 9 969 975 43. Ogedegbe G. Causal mechanisms of masked hypertension: socio-psychological aspects. Blood Press Monit. 2010;15(2):90-2. Ogedegbe G Causal mechanisms of masked hypertension: socio-psychological aspects Blood Press Monit 2010 15 2 90 92 44. Aksoy I, Deinum J, Lenders JW, Thien T. Does masked hypertension exist in healthy volunteers and apparently well-controlled hypertensive patients? Neth J Med. 2006;64(3):72-7. Aksoy I Deinum J Lenders JW Thien T Does masked hypertension exist in healthy volunteers and apparently well-controlled hypertensive patients Neth J Med 2006 64 3 72 77 45. Obara T, Ohkubo T, Kikuya M, Asayama K, Metoki H, Inoue R, et al; J-HOME Study Group. Prevalence of masked uncontrolled and treated white-coat hypertension defined according to the average of morning and evening home blood pressure value: from the Japan Home Versus Office Measurement Evaluation Study. Blood Press Monit. 2005;10(6):311-6. Obara T Ohkubo T Kikuya M Asayama K Metoki H Inoue R et al J-HOME Study Group Prevalence of masked uncontrolled and treated white-coat hypertension defined according to the average of morning and evening home blood pressure value: from the Japan Home Versus Office Measurement Evaluation Study Blood Press Monit 2005 10 6 311 316 46. Ogedegbe G, Pickering TG, Clemow L, Chaplin W, Spruill TM, Albanese GM, et al. The misdiagnosis of hypertension: the role of patient anxiety. Arch Intern Med. 2008;168(22):2459-65. Ogedegbe G Pickering TG Clemow L Chaplin W Spruill TM Albanese GM et al The misdiagnosis of hypertension: the role of patient anxiety Arch Intern Med 2008 168 22 2459 2465 47. Wang GL, Li Y, Staessen JA, Lu L, Wang JG. Anthropometric and lifestyle factors associated with white-coat, masked and sustained hypertension in a Chinese population. J Hypertens. 2007;25(12):2398-405. Wang GL Li Y Staessen JA Lu L Wang JG Anthropometric and lifestyle factors associated with white-coat, masked and sustained hypertension in a Chinese population J Hypertens 2007 25 12 2398 2405 48. Baguet JP, Hammer L, Levy P, Pierre H, Rossini E, Mouret S, et al. Night-time and diastolic hypertension are common and underestimated conditions in newly diagnosed apnoeic patients. J Hypertens. 2005;23(3):521-7. Baguet JP Hammer L Levy P Pierre H Rossini E Mouret S et al Night-time and diastolic hypertension are common and underestimated conditions in newly diagnosed apnoeic patients J Hypertens 2005 23 3 521 527 49. Ungar A, Pepe G, Monami M, Lambertucci L, Torrini M, Baldasseroni S, et al. Isolated ambulatory hypertension is common in outpatients referred to a hypertension center. J Hum Hypertens. 2004;18(12):897-903. Ungar A Pepe G Monami M Lambertucci L Torrini M Baldasseroni S et al Isolated ambulatory hypertension is common in outpatients referred to a hypertension center J Hum Hypertens 2004 18 12 897 903 50. Ogedegbe G, Agyemang C, Ravenell JE. Masked hypertension: evidence of the need to treat. Curr Hypertens Rep. 2010;12(5):349-55. Ogedegbe G Agyemang C Ravenell JE Masked hypertension: evidence of the need to treat Curr Hypertens Rep 2010 12 5 349 355 51. Pickering T, Eguchi K, Kario K. Masked hypertension: a review. Hypertens Res. 2007;30(6):479-88. Pickering T Eguchi K Kario K Masked hypertension: a review Hypertens Res 2007 30 6 479 488 52. Terawaki H, Metoki H, Nakayama M, Ohkubo T, Kikuya M, Asayama K, et al. Masked hypertension determined by self-measured blood pressure at home and chronic kidney disease in the Japanese general population: the Ohasama study. Hypertens Res. 2008;31(12):2129-35. Terawaki H Metoki H Nakayama M Ohkubo T Kikuya M Asayama K et al Masked hypertension determined by self-measured blood pressure at home and chronic kidney disease in the Japanese general population: the Ohasama study Hypertens Res 2008 31 12 2129 2135 53. Kawano Y, Horio T, Matayoshi T, Kamide K. Masked hypertension: subtypes and target organ damage. Clin Exp Hypertens. 2008;30(3):289-96. Kawano Y Horio T Matayoshi T Kamide K Masked hypertension: subtypes and target organ damage Clin Exp Hypertens 2008 30 3 289 296 54. Mallion JM, Genes N, Vaur L, Clerson P, Vaisse B, Bobrie G, et al. Detection of masked hypertension by home blood pressure measurement: is the number of measurements an important issue? Blood Press Monit. 2004;9(6):301-5. Mallion JM Genes N Vaur L Clerson P Vaisse B Bobrie G et al Detection of masked hypertension by home blood pressure measurement: is the number of measurements an important issue? Blood Press Monit 2004 9 6 301 305 55. Head GA, McGrath BP, Mihailidou AS, Nelson MR, Schlaich MP, Stowasser M, et al. Ambulatory blood pressure monitoring in Australia: 2011 consensus position statement. J Hypertens. 2012;30(3):253-66. Head GA McGrath BP Mihailidou AS Nelson MR Schlaich MP Stowasser M et al Ambulatory blood pressure monitoring in Australia: 2011 consensus position statement J Hypertens 2012 30 3 253 266 56. Verdecchia P, Porcellati C, Schillaci G, Borgioni C, Ciucci A, Battistelli M, et al. Ambulatory blood pressure: an independent predictor of prognosis in essential hypertension. Hypertension. 1994;24(6):793-801. Verdecchia P Porcellati C Schillaci G Borgioni C Ciucci A Battistelli M et al Ambulatory blood pressure: an independent predictor of prognosis in essential hypertension Hypertension 1994 24 6 793 801 57. Liu JE, Roman MJ, Pini R, Schwartz JE, Pickering TG, Devereux RB. Cardiac and arterial target organ damage in adults with elevated ambulatory and normal office blood pressure. Ann Intern Med. 1999;131(8):564-72. Liu JE Roman MJ Pini R Schwartz JE Pickering TG Devereux RB Cardiac and arterial target organ damage in adults with elevated ambulatory and normal office blood pressure Ann Intern Med 1999 131 8 564 572 58. Bobrie G, Chatellier G, Genes N, Clerson P, Vaur L, Vaisse B, et al. Cardiovascular prognosis of "masked hypertension" detected by blood pressure self-measurement in elderly treated hypertensive patients. JAMA. 2004;291(11):1342-9. Bobrie G Chatellier G Genes N Clerson P Vaur L Vaisse B et al Cardiovascular prognosis of "masked hypertension" detected by blood pressure self-measurement in elderly treated hypertensive patients JAMA 2004 291 11 1342 1349 59. Cuspidi C, Negri F, Sala C, Mancia G. Masked hypertension and echocardiographic left ventricular hypertrophy: an updated overview. Blood Press Monit. 2012;17(1):8-13. Cuspidi C Negri F Sala C Mancia G Masked hypertension and echocardiographic left ventricular hypertrophy: an updated overview Blood Press Monit 2012 17 1 8 13 60. Hanninen MR, Niiranen TJ, Puukka PJ, Johansson J, Jula AM. Prognostic significance of masked and white-coat hypertension in the general population: the Finn-Home Study. J Hypertens. 2012;30(4):705-12. Hanninen MR Niiranen TJ Puukka PJ Johansson J Jula AM Prognostic significance of masked and white-coat hypertension in the general population: the Finn-Home Study J Hypertens 2012 30 4 705 712 61. Effects of weight loss and sodium reduction intervention on blood pressure and hypertension incidence in overweight people with high-normal blood pressure. The Trials of Hypertension Prevention, phase II. The Trials of Hypertension Prevention Collaborative Research Group. Arch Intern Med. 1997;157(6):657-67. Effects of weight loss and sodium reduction intervention on blood pressure and hypertension incidence in overweight people with high-normal blood pressure. The Trials of Hypertension Prevention, phase II. The Trials of Hypertension Prevention Collaborative Research Group Arch Intern Med 1997 157 6 657 667 62. Appel LJ, Moore TJ, Obarzanek E, Wollmer WM, Svetkey LP, Sacks FM, et al. A clinical trial of the effects of dietary patterns on blood pressure. DASH Collaborative Research Group. N Engl J Med. 1997;336 (16):1117-24. Appel LJ Moore TJ Obarzanek E Wollmer WM Svetkey LP Sacks FM et al A clinical trial of the effects of dietary patterns on blood pressure. DASH Collaborative Research Group N Engl J Med 1997 336 16 1117 1124 63. Sacks FM, Svetkey LP, Vollmer WM, Appel LJ, Bray GA, Harsha D, et al. Effects on blood pressure of reduced dietary sodium and the Dietary Approaches to Stop Hypertension (DASH) diet. DASH-Sodium Collaborative Research Group. N Engl J Med. 2001;344(1):3-10. Sacks FM Svetkey LP Vollmer WM Appel LJ Bray GA Harsha D et al Effects on blood pressure of reduced dietary sodium and the Dietary Approaches to Stop Hypertension (DASH) diet: DASH-Sodium Collaborative Research Group N Engl J Med 2001 344 1 3 10 64. Stevens VJ, Obarzanek E, Cook NR, Lee IM, Appel LJ, West DS, et al. Long-term weight loss and changes in blood pressure: results of the Trials of Hypertension Prevention, phase II. Ann Intern Med. 2001;134(1):1-11. Stevens VJ Obarzanek E Cook NR Lee IM Appel LJ West DS et al Long-term weight loss and changes in blood pressure: results of the Trials of Hypertension Prevention, phase II Ann Intern Med 2001 134 1 1 11 65. Cook NR, Cutler JA, Obarzanek E, Buring JE, Rexrode KM, Kumanyika SK, et al. Long term effects of dietary sodium reduction on cardiovascular disease outcomes: observational follow-up of the trials of hypertension prevention (TOHP). BMJ. 2007;334(7599):885-8. Cook NR Cutler JA Obarzanek E Buring JE Rexrode KM Kumanyika SK et al Long term effects of dietary sodium reduction on cardiovascular disease outcomes: observational follow-up of the trials of hypertension prevention (TOHP) BMJ 2007 334 7599 885 888 66. Appel LJ, Champagne CM, Harsha DW, Cooper LS, Obarzanek E, Elmer PJ, et al. Effects of comprehensive lifestyle modification on blood pressure control: main results of the PREMIER clinical trial. JAMA. 2003;289(16):2083-93. Appel LJ Champagne CM Harsha DW Cooper LS Obarzanek E Elmer PJ et al Effects of comprehensive lifestyle modification on blood pressure control: main results of the PREMIER clinical trial JAMA 2003 289 16 2083 2093 67. Elmer PJ, Obarzanek E, Vollmer WM, Simons-Morton D, Stevens VJ, Young DR, et al. Effects of comprehensive lifestyle modification on diet, weight, physical fitness, and blood pressure control: 18-month results of a randomized trial. Ann Intern Med. 2006;144 (7):485-95. Elmer PJ Obarzanek E Vollmer WM Simons-Morton D Stevens VJ Young DR et al Effects of comprehensive lifestyle modification on diet, weight, physical fitness, and blood pressure control: 18-month results of a randomized trial Ann Intern Med 2006 144 7 485 495 68. Park S, Rink LD, Wallace JP. Accumulation of physical activity leads to a greater blood pressure reduction than a single continuous session, in prehypertension. J Hypertens. 2006;24(9):1761-70. Park S Rink LD Wallace JP Accumulation of physical activity leads to a greater blood pressure reduction than a single continuous session, in prehypertension J Hypertens 2006 24 9 1761 1770 69. Kawano Y. Lifestyle modification for masked hypertension. Curr Hypertens Rev. 2011;7(1):9-12. Kawano Y Lifestyle modification for masked hypertension Curr Hypertens Rev 2011 7 1 9 12 70. Leary AC, Struthers AC, Donnan PT, MacDonald TM, Murphy MB. The morning surge in blood pressure and heart rate is dependent on physical activity after waking. J Hypertens. 2002;20(5):865-70. Leary AC Struthers AC Donnan PT MacDonald TM Murphy MB The morning surge in blood pressure and heart rate is dependent on physical activity after waking J Hypertens 2002 20 5 865 870 71. Verdecchia P, Schilatti G, Borgioni C, Ciucci A, Zampi I, Battistelli M, et al. Cigarette smoking, ambulatory blood pressure and cardiac hypertrophy in essential hypertension. J Hypertens. 1995;13(10):1209-15. Verdecchia P Schilatti G Borgioni C Ciucci A Zampi I Battistelli M et al Cigarette smoking, ambulatory blood pressure and cardiac hypertrophy in essential hypertension J Hypertens 1995 13 10 1209 1215 72. Uzu T, Nakao K, Kume S, Araki H, Isshiki K, Araki S, et al. High sodium intake is associated with masked hypertension in Japanese patients with type 2 diabetes and treated hypertension. Am J Hypertens. 2012;25(11):1170-4. Uzu T Nakao K Kume S Araki H Isshiki K Araki S et al High sodium intake is associated with masked hypertension in Japanese patients with type 2 diabetes and treated hypertension Am J Hypertens 2012 25 11 1170 1174 73. Baguet JP, Lévy P, Barone-Rochette G, Tamisier R, Pierre H, Peeters M, et al. Masked hypertension in obstructive sleep apnea syndrome. J Hypertens. 2008;26(5):885-92. Baguet JP Lévy P Barone-Rochette G Tamisier R Pierre H Peeters M et al Masked hypertension in obstructive sleep apnea syndrome J Hypertens 2008 26 5 885 892 74. Tsai J, Liu J, Kao C, Tomlinson B, Kao P, Chen J, et al. Beneficial effects on blood pressure and lipid profile of programmed exercise training in subjects with white coat hypertension. Am J Hypertens. 2002;15(6):571-6. Tsai J Liu J Kao C Tomlinson B Kao P Chen J et al Beneficial effects on blood pressure and lipid profile of programmed exercise training in subjects with white coat hypertension Am J Hypertens 2002 15 6 571 576 75. Lima AS, Zanetti ML, Miyar LO, Machado MP. Fatores facilitadores / dificultadores para a implementação de um programa educativo por equipe multidisciplinar. Arq Bras Endocrinol Metab. 2003;47(5):568-78. Lima AS Zanetti ML Miyar LO Machado MP Fatores facilitadores / dificultadores para a implementação de um programa educativo por equipe multidisciplinar Arq Bras Endocrinol Metab 2003 47 5 568 578 76. Margolius D, Wong J, Goldman ML, Rouse-Iniguez J, Bodenheimer T. Delegating responsibility from clinicians to nonprofessional personnel: the example of hypertension control. J Am Board Fam Med. 2012;25(2):209-15. Margolius D Wong J Goldman ML Rouse-Iniguez J Bodenheimer T Delegating responsibility from clinicians to nonprofessional personnel: the example of hypertension control J Am Board Fam Med 2012 25 2 209 215 77. Appel LJ; American Society of Hypertension Writing Group. ASH position paper: dietary approaches to lower blood pressure. J Am Soc Hypertens. 2009;3(5):321-31. Appel LJ American Society of Hypertension Writing Group ASH position paper: dietary approaches to lower blood pressure J Am Soc Hypertens 2009 3 5 321 331 78. Hooper L, Bartlett C, Davey Smith G, Ebrahim S. Systematic review of long term effects of advice to reduce dietary salt in adults. BMJ. 2002;325(7365):628. Hooper L Bartlett C Davey Smith G Ebrahim S Systematic review of long term effects of advice to reduce dietary salt in adults BMJ 2002 325 7365 628 79. Fuchs FD, Gus M, Moreira WD, Moraes RS, Rosito GA, Sorucco A, et al. Blood pressure effects of antyhypertensive drugs and lifestyle modification in a Brazilian hypertensive cohort. J Hypertens. 1997;15:783-792. Fuchs FD Gus M Moreira WD Moraes RS Rosito GA Sorucco A et al Blood pressure effects of antyhypertensive drugs and lifestyle modification in a Brazilian hypertensive cohort J Hypertens 1997 15 783 792 80. Selassie A, Wagner CS, Laken ML, Ferguson ML, Ferdinand KC, Egan BM. Progression is accelerated from prehypertension to hypertension in blacks. Hypertension. 2011;58(4):579-87. Selassie A Wagner CS Laken ML Ferguson ML Ferdinand KC Egan BM Progression is accelerated from prehypertension to hypertension in blacks Hypertension 2011 58 4 579 587 81. Fink GD, Arthur C. Corcoran Memorial Lecture. Sympathetic activity, vascular capacitance, and long-term regulation of arterial pressure. Hypertension. 2009;53(2)307-12. Fink GD Arthur C Corcoran Memorial Lecture Sympathetic activity, vascular capacitance, and long-term regulation of arterial pressure Hypertension 2009 53 2 307 312 82. Luders S, Schrader J, Berger J, Unger T, Zidek W, Bohm M, et al. The PHARAO study: prevention of hypertension with the angiotensin-converting enzyme inhibitor ramipril in patients with high-normal blood pressure - a prospective, randomized, controlled prevention trial of the German Hypertension League. J Hypertens. 2008;26(7):1487-96. Luders S Schrader J Berger J Unger T Zidek W Bohm M et al The PHARAO study: prevention of hypertension with the angiotensin-converting enzyme inhibitor ramipril in patients with high-normal blood pressure - a prospective, randomized, controlled prevention trial of the German Hypertension League J Hypertens 2008 26 7 1487 1496 83. Fuchs FD, Fuchs SC, Moreira LB, Gus M, Nóbrega AC, Poli-de-Figueiredo CE, et al. Prevention of hypertension in patients with pre-hypertension: protocol for the PREVER-prevent trial. Trials. 2011;12:65. Fuchs FD Fuchs SC Moreira LB Gus M Nóbrega AC Poli-de-Figueiredo CE et al Prevention of hypertension in patients with pre-hypertension: protocol for the PREVER-prevent trial Trials 2011 12 65 65 84. McInnes G. Pre-hypertension: how low to go and do drugs have a role. Br J Clin Pharmacol. 2012;73(2):187-93. McInnes G Pre-hypertension: how low to go and do drugs have a role Br J Clin Pharmacol 2012 73 2 187 193 85. Thompson AM, Hu T, Eshelbrenner CL, Reynolds K, He J, Bazzano LA. Antihypertensive treatment and secondary prevention of cardiovascular disease events among persons without hypertension: a meta-analysis. JAMA. 2011;305(9):913-22. Thompson AM Hu T Eshelbrenner CL Reynolds K He J Bazzano LA Antihypertensive treatment and secondary prevention of cardiovascular disease events among persons without hypertension: a meta-analysis JAMA 2011 305 9 913 922 86. Mancia G, Bombelli M, Seravalle G, Grassi G. Diagnosis and management of patients with white-coat and masked hypertension. Nat Rev Cardiol. 2011;8(12):686-93. Mancia G Bombelli M Seravalle G Grassi G Diagnosis and management of patients with white-coat and masked hypertension Nat Rev Cardiol 2011 8 12 686 693 87. Phillips RA. Controversies in blood pressure goal guidelines and masked hypertension. Ann NY Acad Sci. 2012;1254:115-22. Phillips RA Controversies in blood pressure goal guidelines and masked hypertension Ann NY Acad Sci 2012 1254 115 122 Special Article I Brazilian Position Paper on Prehypertension, White Coat Hypertension and Masked Hypertension: Diagnosis and Management Alessi Alexandre Brandão Andréa Araujo Paiva Annelise Machado Gomes de Nogueira Armando da Rocha Feitosa Audes Gonzaga Carolina de Campos Amodeo Celso Mion Decio Souza Dilma do Socorro Moraes de Barbosa Eduardo Junior Emilton Lima Nobre Fernando Fuchs Flavio Dani Junior Hilton Chaves Schneider Jamil Cherem Gemelli João Villela-Martin José Fernando Scala Luiz Cesar Nazario Gomes Marco Antonio Mota Malachias Marcus Vinicus Bolivar Morais Nelson Siqueira de Moreira Filho Osni Passarelli Junior Oswaldo Jardim Paulo Cesar Brandão Veiga Miranda Roberto Dischinger Póvoa Rui Fuchs Sandra Cristina Baiocchi Sergio Jardim Thiago Veiga Barroso Weimar Kunz Sebba Brazilian Society of Cardiology Arterial Hypertension Department Brazilian Society of Cardiology Arterial Hypertension Department Mailing Address: Paulo César B. Veiga Jardim, Rua 115-F, nº 135, Setor Sul. CEP 74085-300, Goiânia, GO - Brazil. E-mail: fvjardim.ufg@gmail.com, fvjardim@terra.com.br

Potential Conflict of Interest

No potential conflict of interest relevant to this article was reported.

 Hypertension / therapy Prehypertension / prevention & control White Coat Hypertension Masked Hypertension Introduction

Arterial blood pressure (BP) is a very useful variable in clinical practice. Its measurement is simple, inexpensive and easy; it is worth noting that BP should be accurately obtained, following the recommendations of the VI Brazilian Guidelines on Hypertension (DBH VI)1.

Office BP measurement is the central parameter for the diagnosis, treatment and follow-up of systemic arterial hypertension (SAH), being directly, continuously and independently related to the risk of fatal and non-fatal cardiovascular (CV) events1 - 3.

Thus, the consideration of BP values closer to the upper limits of normality, the so-called prehypertension (PH)2, and intervention on those values have been emphasized over the last decade, because PH represents an important opportunity to prevent established SAH, contributing to reduce the associated CV risk.

Repeated BP measurement at the office allows the diagnosis of hypertension and normotension. To better assess BP behavior, there are methods that analyze BP by using a higher number of measurements, minimizing interferences of the environment, situation and observer. Those alternatives are as follows: 24-hour ambulatory BP monitoring (ABPM); and dwelling BP measurement [home BP monitoring (HBPM) and BP self-measurement (BPSM)]. Based on those methods, two other BP classifications were adopted: white coat hypertension (WCH) and masked hypertension (MH)1 , 3 - 5 (Figure 1).

Classification of blood pressure behavior considering office BP, ABPM and home BP measurements<xref ref-type="bibr" rid="B01">1</xref>. ABPM: ambulatory blood pressure monitoring; BP: blood pressure.

Epidemiological and clinical studies on those conditions are still limited; however, they deserve attention because of their higher CV risk as compared with normotension6 , 7.

This document represents the position of the Brazilian Society of Cardiology Arterial Hypertension Department (DHA/SBC) on the diagnosis and non-drug and drug therapy for PH, WCH and MH, aiming at contributing to a better clinical practice.

 Prehypertension Epidemiology

The term PH was described in 2003 on the American Guideline on Arterial Hypertension1 that emphasized the importance of adopting strict preventive measures in the presence of PH, considering that individuals with such characteristics have a higher incidence of SAH in the following years and greater CV risk than those with optimal BP (lower than 120/80 mm Hg)2 , 3. A study has shown that among prehypertensive individuals aged 40-49 years, the incidence of hypertension in the following years is 80%8.

In the PURE (Prospective Urban and Rural Epidemiological) Study, assessing 153,996 individuals in 17 countries, PH prevalence was 36.8%, greater than the SAH rate (34.3%). Data on the North American adult population have shown a 40% prevalence9.

Prehypertension is known to be often associated with other CV risk factors, such as obesity, insulin resistance, diabetes mellitus, dyslipidemia and other metabolic syndrome phenotypes, resulting in early vascular abnormalities and progression to atherosclerosis10.

 Diagnosis and clinical strategies of identification

Prehypertension has been defined as office measurements of systolic blood pressure (SBP) between 120 and 139 mm Hg and/or of diastolic blood pressure (DBP) between 80 and 89 mmHg2. Its identification depends on regular BP measurement, which is recommended to be performed at least once a year.

The diagnosis of PH is based on BP measurement at the office, but that diagnosis can certainly be improved with 24-hour ABPM and/or HBPM. Such forms of out-of-office BP assessment have the advantage of providing a much higher number of measurements, outside sites where BP is usually taken, representing a more reliable BP registry4 , 5. It is important to identify the presence of MH among prehypertensive individuals.

There is evidence that the increase in left ventricular mass (LVM) in prehypertensive individuals is a strong predictor of the development of SAH within four years, regardless of other metabolic and anthropometric factors associated. The increase in LVM might be associated with a higher daily hemodynamic load that could be detected by measuring BP at the office. Increased BP variability, lack of its drop during sleep or sustained and prolonged increased BP during wakefulness could explain higher LVM values in prehypertensive individuals. In addition, PH progression to hypertension has been associated with increased arterial stiffness11 , 12.

 Prognostic value

Prehypertension is a precursor of SAH, associates with other CV risk factors, and has greater CV morbidity and mortality6 , 13.

In the population assessed in the Framingham study, the following percentages of individuals younger than 65 years developed SAH within a four-year follow-up in the three BP strata considered normal: 5.3% of the individuals with optimal BP; 17.6% of those with normal BP; and 37.3% of those considered to have high-normal BP at the time. For individuals older than 65 years, those rates were 16%, 25.5% and 49.5%, respectively14. Data obtained from two British Health and Lifestyle Surveys conducted seven years apart have been used to form a subsample of 2,048 normotensive individuals, and have demonstrated a greater risk for developing SAH among those with higher BP levels, especially the younger ones15. Other studies have reported that individuals older than 45 years have a 56.4% progression rate to arterial hypertension in three years (56.9% for men and 55.9% for women)16.

A population-based study conducted in Brazil has reported that four out of five prehypertensive individuals aged 40-49 years developed SAH in ten years8.

Regarding the increased risk for CV events of patients with PH, data from longitudinal studies from the Framingham Heart Study have indicated that SBP levels between 130-139 mm Hg and DBP between 85-89 mm Hg are associated with a two-fold increase in the risk for CV diseases (CVD) as compared with 120/80 mmHg levels14. That association proved to be more significant in diabetic individuals and those with higher body mass index (BMI)17. Individuals with PH are more prone to acute myocardial infarction (AMI) or coronary artery disease (CAD) than those considered normotensive18. A Japanese study has reported a 45% increase in the risk of CV events in prehypertensive individuals as compared with normotensive ones, after adjusting for all other traditional risk factors19.

White coat hypertension Epidemiology

The prevalence of WCH varies because of the diversity of the diagnostic criteria involving not only aspects related to BP measurement but also to the populations studied. The mean overall prevalence of WCH, based on four population-based studies, was 13%, and reached 32% among hypertensives in those studies20. In the general population, those values range from 10% to 20%, being more common among children and the elderly, in the female sex, and in non-smokers21 , 22.

The prevalence of WCH is also related to office BP measurements, its percentage being 55% among stage 1 hypertensives, and only 10% among stage 3 hypertensives21. However, among individuals whose DBP at the office exceeds 105 mm Hg, WCH is an unlikely finding23. That phenomenon also occurs among hypertensives undergoing treatment, being called the white coat effect. Muxfeldt et al24 have assessed uncontrolled hypertensive patients on antihypertensive treatment, of whom more than 60% were on three or more drugs and 37% had the white coat effect. In the PAMELA (Pressione Arteriose Monitorate E Loro Associazioni) study, ongoing for ten years, 42.6% of the patients with metabolic syndrome and WCH at the first consultation developed sustained arterial hypertension25.

The greater the BMI, the higher the WCH prevalence. Helvaci et al26, studying the BP behavior of individuals assessed at check-up clinics, have reported the following WCH prevalences: 19.6% for individuals with IMC lower than 18.5 kg/m2; 35.6% for individuals with IMC between 18.5 and 24.9 kg/m2; and 68.4% for overweight individuals (IMC between 25 and 29.9 kg/m2) 26.

The WCH frequency increases with age, and, among individuals older than 65 years, its prevalence usually ranges from 43% to 45%27.

In a follow-up period of up to 6.5 years, Verdecchia et al28 have reported a 37% risk of developing arterial hypertension in individuals with WCH. That percentage related to baseline values of ABPM rather than to office BP.

 Diagnosis and clinical strategies of identification

The diagnosis of WCH requires office and out-of-office BP measurement, be it by use of ABPM or home measurements4. The thresholds recommended are those adopted at the most recent NICE29 and 2013 ESH/ESC3 guidelines, and ESH Position Paper on Ambulatory Blood Pressure Monitoring5, which maintain the values of the JNC 72 and 2003 and 2007 ESH/ESC30 , 31 guidelines, and were based on studies such as the IDACO (International Database on Ambulatory Blood Pressure monitoring in relation to Cardiovascular Outcomes Investigators)32 and Ohasama Study33 (table 1).

Threshold of abnormality to diagnose hypertension on 24-hour ABPM and home BP measurement
Out-of-office measurement SBP and/or DBP (mmHg)
ABPM
24-h mean ≥ 130/80
Wakefulness mean ≥ 135/85
Sleep mean ≥ 120/70
Home measurement ≥ 135/85

ABPM: ambulatory blood pressure monitoring; SBP: systolic blood pressure; DBP: diastolic blood pressure.

White coat hypertension is characterized as follows: 1) increased office BP levels (SBP ≥ 140 mmHg and/or DBP ≥ 90 mmHg); and 2) normal out-of-office BP levels (< 135/85 mmHg) measured on ABPM during wakefulness, or at home (HBPM or BPSM), as shown in table 1 and figures 1 and 2. The European Society of Hypertension recommends that, on ABPM, the diagnosis of WCH requires normal mean values of 24-hour BP and of nocturnal BP5.

Schematic representation of BP behavior at the office and on ABPM or home BP measurement for the diagnosis of white coat hypertension. ABPM: ambulatory blood pressure monitoring; HBPM: home blood pressure monitoring; BPSM: blood pressure self-measurement; SBP: systolic blood pressure; DBP: diastolic blood pressure.

Under such conditions, the diagnosis of office arterial hypertension changes to WCH. Individuals with stage 1-2 office hypertension, with neither co-morbidities nor target organ lesions, should undergo complementary assessment by BP measurement outside the office (figure 3).

Flowchart for the identification of white coat hypertension. ABPM: ambulatory blood pressure monitoring; HBPM: home blood pressure monitoring; BPSM: blood pressure self-measurement.

The white coat effect is defined as an increase in SBP and DBP ≥ 20 mm Hg and 10 mm Hg, respectively34, between office BP measurement and the mean BP on ABPM during wakefulness or home measurements, with no change in the diagnosis of normotension or hypertension.

The use of the term 'home measurements' should increase, replacing the terms HBPM and BPSM. Thus, BPSM should be encouraged with validated equipment, cuffs applied to arm, and periodically tested calibration. It differs mainly from HBPM because of the use of a determined protocol, characterizing that both methods have more similarities than differences and can be used together35.

 Prognostic value

Cardiovascular outcomes related to WCH are still controversial. Studies have suggested that WCH has lower risk, similar to that of normotensive individuals, and that risk tends to increase over time. Meta-analysis carried out with 7,030 individuals has evidenced the existence of increasing CV risk from normotension, to WCH, to MH, and finally, to hypertension20 , 36 - 39.

Regarding the risk of developing hypertension, the PAMELA study has shown that a significantly higher proportion of individuals previously diagnosed with WCH or MH, after ten years were diagnosed with sustained hypertension as compared with previously normotensive individuals25.

 Masked hypertension Epidemiology

Masked hypertension is characterized by normal BP values at the office and abnormal out-of-office BP values, on either ambulatory or dwelling BP measurements (ABPM, HBPM or BPSM)40.

The prevalence of MH is estimated to range from 8% to 20% among adults with no treatment, and to be at least 50% among individuals on drug treatment41. A meta-analysis involving 28 studies has estimated a 16.8% MH prevalence in the general population. Among children, the estimated MH prevalence is 7%42. Higher MH prevalence has been observed when office BP is in the high-normal range41. Office BP within the normal range as compared to abnormal ambulatory values has been attributed, among other factors, to the "regression toward the mean" phenomenon40. Other factors have also correlated with MH30 , 40 , 43 - 48, as shown in Chart 1. In a study involving 3,400 treated hypertensives, the major factors associated with MH were overweight (1.38; 95% CI: 1.09-1.75) and regular alcohol consumption (OR, 1.37; 95% CI: 1.09-1.72)42. In another study, the risk for MH was higher among men than among women [relative risk (RR), 1.14; 95% CI: 1.01-1.28] and among smokers (RR, 1.16; 95% CI: 1.04-1.30)49. Another study has shown that women were less prone than men to have MH (OR, 0.39; 95% CI: 0.22- 0.68)47.

Factors related to the presence of masked hypertension<xref ref-type="bibr" rid="B02">2</xref> <sup>,</sup> <xref ref-type="bibr" rid="B04">4</xref> <sup>-</sup> <xref ref-type="bibr" rid="B11">11</xref>
Male sex
Young age
Family history of arterial hypertension
Smoking habit
Alcohol consumption
Increased physical activity
Exertion-induced hypertension
Occasionally increased BP measurements
Obesity
Diabetes
Chronic kidney disease
Left ventricular hypertrophy
Multiple risk factors
Sleep apnea
Psychosocial factors: anxiety, interpersonal conflicts, stress at workplace

Classically, the presence of MH occurs among untreated individuals. Recently, the literature has emphasized the occurrence of normal office BP and elevated out-of-office BP values in treated individuals. Lower levels of anxiety and the use of antihypertensive drugs only before the medical consultation, with a drug action peak at the time of medical examination, has also been listed as causing factors44 , 46 , 50.

 Diagnosis and clinical strategies of identification

Masked hypertension refers to untreated patients with systematically normal office BP measurements (BP < 140/90 mm Hg) and elevated BP on ABPM or at home measurements - mean BP during wakefulness or mean home BP ≥ 135/85 mm Hg51 , 52 (table 1 and figures 1 and 4). It is worth noting the position of the European Society of Hypertension for ABPM, which has also considered the elevated means of 24-hour and nocturnal BP measurements as criteria for MH diagnosis, even with normal mean BP during wakefulness5.

Schematic representation of BP behavior at the office and on ABPM or home BP measurement for the diagnosis of masked hypertension. ABPM: ambulatory blood pressure monitoring; HBPM: home blood pressure monitoring; BPSM: blood pressure self-measurement; SBP: systolic blood pressure; DBP: diastolic blood pressure.

The conditions listed on Chart 1 are related to MH, and, when present, the diagnosis of MH can be suspected, and ABPM should be considered for a more adequate analysis of the actual BP behavior. The presence of target-organ lesions and the report of repeated high out-of-office BP measurements should raise suspicion of MH1 , 3 - 5 , 48 , 53 , 54.

Masked hypertension can also be identified based on repeated BP measurements in the morning and afternoon with proper sensitivity and specificity7. However, several authors have questioned the reproducibility in the long run of the measurements obtained in that way55.

Prognostic value

The prognostic value of MH is controversial; while some studies have confirmed its greater CV risk, others have failed to show such relationship. Several authors have reported that ABPM and home BP measurements of hypertensives are better independent predictors of both target-organ lesions56 , 57 and CV risk58 than office BP measurement. However, Cuspidi et al59, analyzing 13 studies in an attempt to relate MH and left ventricular hypertrophy (LVH), have concluded that the relationship between MH and the development of LVH was limited59.

On the other hand, concentric remodeling and LVH, thickening of the intima-media layer, carotid atherosclerotic plaques and microalbuminuria were more prevalent in MH than in the normotensive population56.

Hanninen et al60, assessing the prognostic value of MH in a general population sample in Finland, have included 2,046 normotensive and hypertensive individuals with different CV risk factors. Those authors have reported that, assessing the CV risk by measuring home BP, patients with MH have a higher CV risk adjusted for age as compared with that of normotensive individuals. However, MH was not an independent predictor of CV risk when the baseline home BP measurement was adjusted for other traditional risk factors. They have concluded that home BP values associated with other traditional risk factors are sufficient for CV risk stratification.

Meta-analyses of prospective studies have indicated a two fold increase in the risk for CV events in MH as compared with true normotension, an incidence similar to that observed in true SAH. The non-detection of MH and the consequent lack of treatment might have contributed to that result20 , 37 , 41.

 Non-drug treatment for prehypertension, white coat hypertension and masked hypertension: efficacy and difficulties for implementation

There is no doubt about the benefits obtained with changes in lifestyle (CLS) for individuals with SAH and prehypertension, and there are good indications that they extend to those with WCH, as well as to those with MH1 , 3.

The major CLS aimed at that purpose are as follows: weight control; change to the DASH diet (rich in fruits, vegetables, fibers, minerals and low-fat dairy products); reduced salt intake; reduced alcohol consumption; smoking cessation; physical exercise practice; and psychosocial stress control1 , 3.

Several clinical studies assessing those measures have shown a significant BP reduction in hypertensive and prehypertensive individuals, and a delay in the appearance of SAH in the latter61 - 68.

Regarding WCH, the encouragement of CLS is based on the following reasons: WCH is not harmless, because individuals with WCH can have changes in target organs; CLS should be the initial strategy to reduce BP in any type of BP behavior change; CLS are recommended as an important strategy to prevent or delay the appearance of SAH in the general population; patients with WCH are more likely to develop sustained SAH; CLS have clear benefits to other CV risk factors; the drug treatment of WCH is still controversial1 , 3 , 20.

In masked hypertension, the recommendations can be more specific according to the period of the day in which BP increases, such as morning, daytime and nocturnal hypertension69.

The reduction in alcohol consumption and in physical and mental stress is recommended for patients with morning hypertension70. Regarding hypertension during wakefulness, smoking cessation is necessary, as well as physical and mental stress control71. Those with hypertension during sleep should undergo salt restriction, because that type of hypertension is more often observed in salt-sensitive individuals72, as well as weight reduction, especially the obese individuals with obstructive sleep apnea syndrome73.

In addition to close follow-up by a medical professional, the multiprofessional team plays a fundamental role, motivating adherence to treatment and assuring that changes are permanent1 , 3 , 74 - 76.

Despite evidence, the great limitation and reason of distrust is the effectiveness of those CLS measures out of the context of clinical trials. In real life, even the most motivated individuals face difficulties to sustain CLS, pressed by cultural forces, deep-rooted habits, society rules and commercial interests that encourage sedentary lifestyle, improper diet, and excessive caloric intake77. This raises expectations about the potential of drug alternatives to face those situations78 , 79.

Drug treatment Prehypertension

Prehypertension represents an intermediate stage for established SAH, and its conversion to sustained arterial hypertension is more accelerated in black individuals8 , 80. The renin-angiotensin-aldosterone system (RAAS) is frequently activated in prehypertensive individuals81. That suggests that the early intervention with drugs might reduce the incidence of sustained hypertension and prevent the progression of CVD.

The Trial of Preventing Hypertension (TROPHY)13 and the Prevention of Hypertension with the Angiotensin Converting Enzyme Inhibitor Ramipril in Patients with High-Normal Blood Pressure (PHARAO) Study82 were the first to show that RAAS inhibitors reduce the incidence of hypertension. The TROPHY study has assessed 772 individuals with BP of 130-139/85-89 mm Hg, randomized to receive either placebo or candesartan (16 mg/day - intervention group). All individuals were instructed about CLS. After four years, a lower incidence of SAH (9.8%) was observed in the intervention group, with a 16% reduction in RR and number necessary to treat (NNT) of 1113. That study has been questioned regarding some methodological aspects, which might have overvalued its results. The PHARAO study has assessed 1,008 prehypertensive individuals with BP of 130-139/85-89 mm Hg, for three years, who have been randomly allocated to receive 5 mg/day of ramipril or placebo. The ramipril group showed a 34% reduction in RR in the incidence of SAH assessed by using office BP (NNT = 9) and ABPM (32.5% vs. 53.0%), with an increase in the incidence of cough (4.8% vs. 0.4%)82. However, if those are long term benefits, if they prevent CV events and are cost-effective is yet to be clarified.

Current guidelines recommend CLS to all prehypertensive individuals, and drug intervention only to those with normal high BP values at high risk, with CVD or established kidney disease, metabolic syndrome or diabetes1, at medical discretion. It is worth noting that so far there is only evidence for the use of RAAS blockers. Recent European guidelines on hypertension have highlighted the lack of sufficient scientific evidence supporting the beginning of drug treatment for normal-high BP levels.

In face of the evidence above and the low effectiveness of CLS in the long run, the use of low doses of antihypertensive drugs to prehypertensive individuals with no CVD, but at high risk to develop sustained arterial hypertension, should be considered83 - 85.

 White-coat hypertension (WCH)

The benefit of drug treatment to WCH remains undefined, because there has never been a clinical trial specifically designed to test that hypothesis. In addition, large clinical studies designed to show target-organ protection with antihypertensive treatment have never used ABPM or home BP measurements, except in small subgroups, with a small number of CV events, which have not yielded definitive conclusions.

In the lack of direct evidence, and in the presence of high or very high CV risk (concomitance of CVD or kidney disease, target-organ lesions, metabolic syndrome or diabetes), antihypertensive treatment can be considered for WCH. Thus, assessing CV risk factors and determining the risk of individuals with WCH are required for customized decision making about their antihypertensive treatment86.

Those patients should be followed up by using ABPM or home BP measurements.

 Masked hypertension (MH)

There is plenty of scientific evidence of the negative impact of MH on CV morbidity and mortality that justify identifying and treating those patients similarly to office hypertensive patients42.

Clinical studies on patients with MH demonstrating the relationship between BP decrease and CV risk reduction still lack. The beginning of drug treatment for patients with MH is based on the fact that they actually have out of office hypertension, with CV risk similar to that of untreated hypertensives50 , 87.

Patients with MH should be stratified and treated similarly to conventional hypertensives50. The efficacy of antihypertensive treatment should be assessed by using out-of-office BP measurement.

Study Association

This study is not associated with any post-graduation program.

Sources of Funding

There were no external funding sources for this study.