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  <front>
    <journal-meta>
      <journal-id journal-id-type="publisher-id">abc</journal-id>
      <journal-title-group>
        <journal-title>Arquivos Brasileiros de Cardiologia</journal-title>
        <abbrev-journal-title abbrev-type="publisher">Arq. Bras. Cardiol.</abbrev-journal-title>
      </journal-title-group>
      <issn pub-type="ppub">0066-782X</issn>
      <issn pub-type="epub">1678-4170</issn>
      <publisher>
        <publisher-name>Sociedade Brasileira de Cardiologia - SBC</publisher-name>
        <publisher-loc>S&#227;o Paulo, SP, Brazil</publisher-loc>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v3">bX57JFffFKVMyDTgRk7vtYn</article-id>
      <article-id pub-id-type="other">00010</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v2">S0066-782X2008001600010</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v1">S0066-782X(08)09100410</article-id>
      <article-id pub-id-type="doi">10.1590/S0066-782X2008001600010</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Artigos Originais</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Teste de respira&#231;&#227;o lenta aumenta a suspeita da hipertens&#227;o do avental branco no consult&#243;rio</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Thalenberg</surname>
            <given-names>Jos&#233; Marcos</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>P&#243;voa</surname>
            <given-names>Rui Manoel dos Santos</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Bombig</surname>
            <given-names>Maria Teresa Nogueira</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>S&#225;</surname>
            <given-names>Gustavo Andr&#233; Costa de</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Atallah</surname>
            <given-names>&#193;lvaro Nagib</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Luna Filho</surname>
            <given-names>Br&#225;ulio</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
      </contrib-group>
      <aff id="aff01">
        <addr-line>
          <named-content content-type="city">S&#227;o Paulo</named-content>
          <named-content content-type="state">S&#227;o Paulo</named-content>
        </addr-line>
        <institution content-type="orgname">Universidade Federal de S&#227;o Paulo</institution>
        <country country="BR">Brazil</country>
      </aff>
      <pub-date date-type="collection" publication-format="electronic">
        <month>10</month>
        <year>2008</year>
      </pub-date>
      <volume>91</volume>
      <issue>4</issue>
      <fpage>267</fpage>
      <lpage>273</lpage>
      <history>
        <date date-type="rev-recd">
          <day>04</day>
          <month>02</month>
          <year>2008</year>
        </date>
        <date date-type="received">
          <day>08</day>
          <month>12</month>
          <year>2007</year>
        </date>
        <date date-type="accepted">
          <day>26</day>
          <month>02</month>
          <year>2008</year>
        </date>
      </history>
      <permissions>
        <license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by-nc/4.0/" xml:lang="en">
          <license-p>This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.</license-p>
        </license>
      </permissions>
      <abstract>
        <p>FUNDAMENTO: Seria &#250;til dispor de um teste cl&#237;nico que aumentasse a suspeita da hipertens&#227;o do avental branco (HAB) durante a consulta. OBJETIVO: Avaliar o teste de respira&#231;&#227;o lenta (TRL) na diferencia&#231;&#227;o entre hipertens&#227;o e HAB. M&#201;TODOS: Cento e um pacientes hipertensos selecionados em triagem tiveram a medica&#231;&#227;o suspensa por duas a tr&#234;s semanas. A press&#227;o arterial (PA) foi medida antes e depois do TRL em duas visitas. O teste consistiu em respirar por 1 minuto na freq&#252;&#234;ncia de um ciclo respirat&#243;rio a cada 10 segundos. Dois crit&#233;rios diagn&#243;sticos foram comparados: 1- queda da PA diast&#243;lica &gt;10% em pelo menos uma consulta, ou 2- queda da PA para n&#237;veis normais (&lt;140/90 mmHg) em pelo menos uma consulta. A MAPA foi realizada de forma cega &#224;s medidas cl&#237;nicas. RESULTADOS: Setenta e uma mulheres e 30 homens, idade m&#233;dia 51+10 anos, m&#233;dia pr&#233; e p&#243;s-teste de 152+17/ 99+11 e 140+18/ 91+11 mmHg. Nove pacientes tiveram medidas cl&#237;nicas e ambulatoriais normais. De 92 pacientes, 28 (30%) foram classificados como HAB; 15 tiveram teste positivo para o crit&#233;rio 1, e 21 para o crit&#233;rio 2. Entre 64 (70%) hipertensos, 14 testaram positivo para o crit&#233;rio 1, e 12 para o crit&#233;rio 2. Sensibilidade e especificidade (95% IC): 0,54 (0,36-0,71) e 0,78 (0,67-0,87) crit&#233;rio 1; 0,75 (0,57-0,87) e 0,81 (0,70-0,89) crit&#233;rio 2. CONCLUS&#195;O: O TRL mostrou aumento da suspeita cl&#237;nica de HAB em duas consultas ao utilizar o crit&#233;rio de normaliza&#231;&#227;o da PA. Isso sugere que esse teste pode auxiliar na otimiza&#231;&#227;o dos pedidos de MAPA para casos suspeitos.</p>
      </abstract>
      <kwd-group xml:lang="pt" kwd-group-type="author-generated">
        <kwd>Hipertens&#227;o</kwd>
        <kwd>testes de fun&#231;&#227;o respirat&#243;ria</kwd>
        <kwd>monitoriza&#231;&#227;o ambulatorial da press&#227;o arterial</kwd>
      </kwd-group>
      <pub-date publication-format="electronic" date-type="pub">
        <day>11</day>
        <month>11</month>
        <year>2008</year>
      </pub-date>
    </article-meta>
  </front>
  <body>
    <p>ARTIGO ORIGINAL </p>
    <p> HIPERTENS&#195;O ARTERIAL SIST&#202;MICA</p>
    <p>
      <bold>Teste de respira&#231;&#227;o lenta aumenta a suspeita da hipertens&#227;o do avental branco no consult&#243;rio</bold>
    </p>
    <p>
      <bold>Jos&#233; Marcos Thalenberg; Rui Manoel dos Santos P&#243;voa; Maria Teresa Nogueira Bombig; Gustavo Andr&#233; Costa de S&#225;; &#193;lvaro Nagib Atallah; Br&#225;ulio Luna Filho</bold>
    </p>
    <p>Universidade Federal de S&#227;o Paulo, S&#227;o Paulo, SP - Brasil</p>
    <p>
      <xref ref-type="corresp" rid="back">Correspond&#234;ncia</xref>
    </p>
    <p>
      <bold>RESUMO</bold>
    </p>
    <p><bold>FUNDAMENTO:</bold> Seria &#250;til dispor de um teste cl&#237;nico que aumentasse a suspeita da hipertens&#227;o do avental branco (HAB) durante a consulta. </p>
    <p><bold>OBJETIVO:</bold> Avaliar o teste de respira&#231;&#227;o lenta (TRL) na diferencia&#231;&#227;o entre hipertens&#227;o e HAB. </p>
    <p><bold>M&#201;TODOS:</bold> Cento e um pacientes hipertensos selecionados em triagem tiveram a medica&#231;&#227;o suspensa por duas a tr&#234;s semanas. A press&#227;o arterial (PA) foi medida antes e depois do TRL em duas visitas. O teste consistiu em respirar por 1 minuto na freq&#252;&#234;ncia de um ciclo respirat&#243;rio a cada 10 segundos. Dois crit&#233;rios diagn&#243;sticos foram comparados: 1- queda da PA diast&#243;lica <underline>&gt;</underline>10% em pelo menos uma consulta, ou 2- queda da PA para n&#237;veis normais (&lt;140/90 mmHg) em pelo menos uma consulta. A MAPA foi realizada de forma cega &#224;s medidas cl&#237;nicas. </p>
    <p><bold>RESULTADOS:</bold> Setenta e uma mulheres e 30 homens, idade m&#233;dia 51<underline>+</underline>10 anos, m&#233;dia pr&#233; e p&#243;s-teste de 152<underline>+</underline>17/ 99<underline>+</underline>11 e 140<underline>+</underline>18/ 91<underline>+</underline>11 mmHg. Nove pacientes tiveram medidas cl&#237;nicas e ambulatoriais normais. De 92 pacientes, 28 (30%) foram classificados como HAB; 15 tiveram teste positivo para o crit&#233;rio 1, e 21 para o crit&#233;rio 2. Entre 64 (70%) hipertensos, 14 testaram positivo para o crit&#233;rio 1, e 12 para o crit&#233;rio 2. Sensibilidade e especificidade (95% IC): 0,54 (0,36-0,71) e 0,78 (0,67-0,87) crit&#233;rio 1; 0,75 (0,57-0,87) e 0,81 (0,70-0,89) crit&#233;rio 2. </p>
    <p><bold>CONCLUS&#195;O:</bold> O TRL mostrou aumento da suspeita cl&#237;nica de HAB em duas consultas ao utilizar o crit&#233;rio de normaliza&#231;&#227;o da PA. Isso sugere que esse teste pode auxiliar na otimiza&#231;&#227;o dos pedidos de MAPA para casos suspeitos.</p>
    <p><bold>Palavras-chave:</bold> Hipertens&#227;o / diagn&#243;stico, testes de fun&#231;&#227;o respirat&#243;ria, monitoriza&#231;&#227;o ambulatorial da press&#227;o arterial.</p>
    <p>
      <bold>Introdu&#231;&#227;o</bold>
    </p>
    <p>A hipertens&#227;o do avental branco (HAB), designa&#231;&#227;o mais utilizada da hipertens&#227;o isolada de consult&#243;rio, &#233; definida como a presen&#231;a de press&#227;o arterial (PA) persistentemente elevada em ambiente m&#233;dico e leituras normais fora desse<sup>1</sup>. Afeta de 15% a 30% de todos os hipertensos presum&#237;veis<sup>2</sup>. Essa condi&#231;&#227;o pode levar a tratamento medicamentoso desnecess&#225;rio, com repercuss&#245;es para pacientes e sistemas de sa&#250;de<sup>3</sup>. Entretanto, a HAB deve ser considerada um estado pr&#233;-hipertensivo<sup>4,5</sup> e n&#227;o inocente<sup>6,7</sup> que necessita um seguimento mais intenso. O diagn&#243;stico da HAB requer preferencialmente o uso de monitoriza&#231;&#227;o ambulatorial da PA (MAPA)<sup>8</sup>. N&#227;o obstante, a falta de caracter&#237;sticas cl&#237;nicas particulares &#224; HAB &#233; um fator que restringe os pedidos de MAPA para fins diagn&#243;sticos<sup>9</sup>.</p>
    <p>A respira&#231;&#227;o lenta, na freq&#252;&#234;ncia de 0.1 Hz (seis ciclos respirat&#243;rios por minuto, um ciclo a cada 10 segundos), mostrou-se efetiva em aumentar a oxigena&#231;&#227;o sang&#252;&#237;nea, a toler&#226;ncia ao exerc&#237;cio, a sensibilidade do barorreflexo<sup>10,11</sup> e diminuir a PA em indiv&#237;duos hipertensos<sup>11</sup>. Presume-se que essa freq&#252;&#234;ncia promova a sincroniza&#231;&#227;o entre a respira&#231;&#227;o e ritmos cardiovasculares inatos (as ondas de Mayer, um ritmo de 10 segundos em seres humanos) com uma conseq&#252;ente modula&#231;&#227;o das atividades auton&#244;micas centrais e perif&#233;ricas (barorreflexo)<sup>12</sup>. Na freq&#252;&#234;ncia de cinco ciclos por minuto, a respira&#231;&#227;o lenta produziu uma pequena diferen&#231;a na queda da press&#227;o diast&#243;lica entre indiv&#237;duos hipertensos e naqueles com HAB, quando aplicada em uma &#250;nica consulta<sup>13</sup>. O objetivo deste estudo foi aprimorar a aplica&#231;&#227;o do teste de respira&#231;&#227;o lenta (TRL), o que poderia aumentar a suspeita da HAB no consult&#243;rio e conseq&#252;entemente otimizar os pedidos de MAPA para os casos suspeitos.</p>
    <p>
      <bold>M&#233;todos</bold>
    </p>
    <p>
      <bold>Desenho do estudo e pacientes</bold>
    </p>
    <p>Neste estudo transversal de acur&#225;cia, 101 pacientes encaminhados ao Setor de Cardiopatia Hipertensiva da Universidade Federal de S&#227;o Paulo (Unifesp), entre mar&#231;o de 2003 e mar&#231;o de 2005, foram avaliados em consulta inicial de triagem. A avalia&#231;&#227;o constou de question&#225;rio estruturado e interpreta&#231;&#227;o de exames laboratoriais e eletrocardiograma que constam da rotina do setor. O question&#225;rio teve entre seus quesitos: tempo de diagn&#243;stico da hipertens&#227;o, medica&#231;&#227;o anti-hipertensiva utilizada (nome e dosagem), outros medicamentos utilizados, <italic>status</italic> para tabagismo e etilismo, outras mol&#233;stias existentes, interna&#231;&#245;es hospitalares (incluindo atendimento para urg&#234;ncias/emerg&#234;ncias hipertensivas). Os crit&#233;rios de inclus&#227;o foram: &#224; triagem, adultos (idade <underline>&gt;</underline> 18 anos) com PA sist&#243;lica (PAS) <underline>&gt;</underline> 140 e &lt; 180 mmHg ou diast&#243;lica (PAD) <underline>&gt;</underline> 90 e &lt; 110 mmHg ou aqueles em uso de medica&#231;&#227;o anti-hipertensiva e PA &lt; 180/110 mmHg. Foram exclu&#237;dos: pacientes com hist&#243;rico de atendimento para crises hipertensivas de qualquer origem, hipertens&#227;o secund&#225;ria, diabete melito, fibrila&#231;&#227;o atrial, angina inst&#225;vel ou de in&#237;cio recente, valvopatias com classe funcional &gt; 1, doen&#231;a pulmonar obstrutiva cr&#244;nica moderada a grave, creatinina s&#233;rica <underline>&gt;</underline> 1,5 mg/dl, &#237;ndice de massa corp&#243;rea <underline>&gt;</underline> 35, a presen&#231;a do &#237;ndice de Sokolow-Lyon (SV 1, + R V 5/V 6 <underline>&gt;</underline> 35 mm) ao ECG e etilismo. O consentimento informado foi obtido previamente de todos os pacientes e o protocolo foi aprovado pelo Comit&#234; de &#201;tica em Pesquisa da institui&#231;&#227;o.</p>
    <p>
      <bold>Teste de respira&#231;&#227;o lenta e medidas da PA</bold>
    </p>
    <p>Os pacientes selecionados foram avaliados duas a tr&#234;s semanas ap&#243;s a suspens&#227;o da medica&#231;&#227;o anti-hipertensiva<sup>14</sup>. A determina&#231;&#227;o auscultat&#243;ria da PA (ru&#237;dos de Korotkoff I e V) foi obtida com um esfigmoman&#244;metro de merc&#250;rio (Wan Med, S&#227;o Paulo, Brasil) com gradua&#231;&#227;o de 2 mm e bolsas de tamanho adequado &#224; circunfer&#234;ncia do bra&#231;o. Com o paciente sentado, mediu-se a PA em ambos os bra&#231;os e escolheu-se o bra&#231;o de maior PA. Ap&#243;s 2 minutos, procedeu-se uma nova aferi&#231;&#227;o no mesmo bra&#231;o. Caso fossem encontradas diferen&#231;as na PAD maiores que 5 mmHg, repetia-se o procedimento at&#233; que se obtivesse medida com diferen&#231;a menor. Com o manguito posicionado no bra&#231;o escolhido, submeteu-se o paciente ao TRL, que consistiu em induzir respira&#231;&#227;o lenta durante um minuto na freq&#252;&#234;ncia de 0,1 Hz (um ciclo respirat&#243;rio a cada 10 segundos). O paciente foi instru&#237;do pelo m&#233;dico a simular o padr&#227;o respirat&#243;rio baseado em rel&#243;gio anal&#243;gico colocado sobre a mesa. Imediatamente ap&#243;s, procedeu-se &#224; medi&#231;&#227;o &#250;nica da PA no bra&#231;o previamente determinado. A freq&#252;&#234;ncia de pulso foi estimada por meio de contagem de 30 segundos, pelo pulso radial, imediatamente ap&#243;s as medidas pr&#233; e p&#243;s-teste.</p>
    <p>Na seq&#252;&#234;ncia imediata, foi instalado monitor para realiza&#231;&#227;o de MAPA de 24 horas (Dyna-MAPA, Cardios Sistemas, S&#227;o Paulo, Brasil; equivalente ao Mobil-O-Graph, I.E.M., Stolberg, Alemanha) com manguito apropriado colocado no bra&#231;o n&#227;o dominante e programado para aferir a PA a cada 15 minutos (vig&#237;lia) e 30 minutos (sono). Os hor&#225;rios de dormir e despertar foram estabelecidos individualmente e checados com os registros do di&#225;rio. No dia seguinte, ap&#243;s a retirada do monitor, foram realizados os mesmos procedimentos descritos anteriormente para mensura&#231;&#227;o da PA antes e depois do TRL em nova consulta. A interpreta&#231;&#227;o dos resultados da MAPA foi feita de maneira cega em rela&#231;&#227;o &#224;s medidas cl&#237;nicas e de acordo com as diretrizes brasileiras<sup>15</sup>. Consideramos v&#225;lidos relat&#243;rios com pelo menos 50 medidas de vig&#237;lia.</p>
    <p>
      <bold>Reprodutibilidade</bold>
    </p>
    <p>A reprodutibilidade interobservadores foi averiguada a partir de medidas obtidas separadamente por um segundo m&#233;dico que testou 20 pacientes por duas vezes, imediatamente ap&#243;s as consultas do primeiro observador. Cada m&#233;dico realizou o atendimento isoladamente, sem nenhum observador admitido durante o procedimento para evitar eleva&#231;&#227;o de PA do paciente<sup>16</sup>. Todas as medidas cl&#237;nicas foram obtidas no per&#237;odo da manh&#227; entre 11h e 12h.</p>
    <p>
      <bold>Crit&#233;rios diagn&#243;sticos</bold>
    </p>
    <p>Consideramos como HAB a exist&#234;ncia de medidas de consult&#243;rio <underline>&gt;</underline> 140 mmHg (PAS) ou <underline>&gt;</underline> 90 mmHg (PAD) nas duas consultas (tamb&#233;m na triagem se o paciente n&#227;o estivesse tomando medica&#231;&#227;o) e m&#233;dia de vig&#237;lia da MAPA &lt; 135 mmHg (PAS) e &lt; 85 mmHg (PAD).</p>
    <p>Foram comparados dois crit&#233;rios como resposta positiva ao TRL para o diagn&#243;stico da HAB.</p>
    <p><bold>Crit&#233;rio 1</bold>) queda da PAD <underline>&gt;</underline> 10% em pelo menos uma das duas consultas.</p>
    <p><bold>Crit&#233;rio 2</bold>) queda da PA para n&#237;veis de normalidade, ou seja, PAS &lt; 140 e PAD &lt; 90 mmHg em pelo menos uma das duas consultas.</p>
    <p>
      <bold>An&#225;lise estat&#237;stica</bold>
    </p>
    <p>Considerando uma preval&#234;ncia m&#233;dia de 20% de HAB, erro alfa de 5% e poder estat&#237;stico da amostra de 90%, estimamos necess&#225;rios 92 indiv&#237;duos com diagn&#243;stico presum&#237;vel de HA. Os resultados foram expressos em m&#233;dia e desvio padr&#227;o (DP). Foram utilizados os testes t de Student pareado e o teste do Qui-quadrado para an&#225;lise dos resultados. O desempenho do TRL foi avaliado pela determina&#231;&#227;o da sensibilidade, especificidade, valores preditivos e raz&#245;es de probabilidade, com os respectivos intervalos de confian&#231;a em 95%. Para a avalia&#231;&#227;o da reprodutibilidade interobservadores do TRL foi utilizado o teste de Kappa. Utilizamos para os c&#225;lculos os programas <italic>Microsoft Excel e Confidence Interval Analysis, version 2</italic>.</p>
    <p>A <xref ref-type="fig" rid="fig1">fig. 1</xref> resume o m&#233;todo do presente estudo.</p>
    <fig id="fig1">
      <graphic xlink:href="1678-4170-abc-91-04-0267-00010-gf01.jpg"/></fig>
    <p>
      <bold>Resultados</bold>
    </p>
    <p>
      <bold>Algumas caracter&#237;sticas da amostra</bold>
    </p>
    <p>A casu&#237;stica constou de 71 mulheres e 30 homens, com idade m&#233;dia de 51&#177;10 anos. Participaram 57 pacientes brancos, 40 negros e quatro amarelos. Dez pacientes tinham idade <underline>&gt;</underline> 65 anos (sete mulheres). Noventa e quatro pacientes utilizavam medica&#231;&#227;o anti-hipertensiva. Desses, 17 estavam em monoterapia, 74 utilizavam duas drogas e tr&#234;s pacientes, tr&#234;s drogas (os &#250;ltimos em uso de doses sub-&#243;timas). As drogas utilizadas pertenciam &#224;s seguintes categorias: diur&#233;ticos tiaz&#237;dicos, betabloqueadores, bloqueadores de canais de c&#225;lcio diidropirid&#237;nicos e inibidores da enzima conversora de angiotensina.</p>
    <p>
      <bold>Classifica&#231;&#227;o ap&#243;s a MAPA</bold>
    </p>
    <p>As m&#233;dias da PA pr&#233; e p&#243;s-teste foram 152&#177;17 / 99&#177;11 e 140&#177;18 / 91&#177;11 mmHg, respectivamente.</p>
    <p>Nove pacientes apresentaram medidas cl&#237;nicas e ambulatoriais normais ap&#243;s a retirada da medica&#231;&#227;o. Dos 92 restantes, 28 (30%) foram classificados como HAB (35% das mulheres e 20% dos homens) e 64 (70%) como hipertensos (HT).</p>
    <p>A <xref ref-type="table" rid="tab1">tabela 1</xref> mostra as m&#233;dias da PA (&#177;DP) na primeira e segunda consultas antes e depois da aplica&#231;&#227;o do TRL e as m&#233;dias de vig&#237;lia da MAPA (&#177;DP) em rela&#231;&#227;o aos grupos HAB e HT. Conforme o esperado, as m&#233;dias pr&#233;-teste do grupo HAB foram mais baixas do que as do grupo HT. Observou-se queda espont&#226;nea da PA pr&#233;-teste entre as consultas 1 e 2 nos dois grupos. Observou-se tamb&#233;m queda significante da PA sist&#243;lica e diast&#243;lica ap&#243;s o teste nos dois grupos. A queda maior foi registrada na consulta 2 do grupo HAB; a menor, na consulta 1 do grupo HT. N&#227;o houve diferen&#231;a significante entre as m&#233;dias da freq&#252;&#234;ncia de pulso pr&#233; e p&#243;s-teste para ambos os grupos.</p>
    <table-wrap id="tab1">
      <graphic xlink:href="1678-4170-abc-91-04-0267-00010-gt01.jpg"/></table-wrap>
    <p>A <xref ref-type="table" rid="tab2">tabela 2</xref> mostra as respostas obtidas para os crit&#233;rios 1 e 2 ap&#243;s a aplica&#231;&#227;o do TRL.</p>
    <table-wrap id="tab2">
      <graphic xlink:href="1678-4170-abc-91-04-0267-00010-gt02.jpg"/></table-wrap>
    <p>Para o grupo HAB e de acordo com o crit&#233;rio 1, oito pacientes foram identificados na consulta 1 e sete, na consulta 2; quatro pacientes responderam positivamente ao TRL nas duas consultas. Em rela&#231;&#227;o ao crit&#233;rio 2, 12 pacientes foram identificados na consulta 1 e nove, na consulta 2; nove pacientes responderam positivamente ao TRL nas duas consultas. Respostas positivas aos dois crit&#233;rios foram observadas em 12 pacientes, e cinco n&#227;o foram identificados por nenhum dos crit&#233;rios.</p>
    <p>As <xref ref-type="table" rid="t3">tabelas 3</xref> e <xref ref-type="table" rid="t4">4</xref> mostram as respostas ao TRL (positivas ou negativas) pelos crit&#233;rios 1 e 2, de acordo com os est&#225;gios de hipertens&#227;o definidos pela V Diretrizes Brasileiras<sup>17</sup> e pelas medidas registradas na consulta 2. No grupo HAB, 25 indiv&#237;duos tiveram medidas cl&#237;nicas compat&#237;veis com HA est&#225;gio 1; os outros tr&#234;s, com HA est&#225;gio 2. No grupo HT, 35 indiv&#237;duos tiveram medidas cl&#237;nicas compat&#237;veis com HA est&#225;gio 1; 24, com HA est&#225;gio 2; e cinco, com HA est&#225;gio 3. Para os pacientes com PA compat&#237;vel com o est&#225;gio 1, houve diferen&#231;a significante entre HT e HAB na resposta ao teste para o crit&#233;rio 2 (p&lt;0,003), mas n&#227;o para o crit&#233;rio 1 (p&lt;0,26).</p>
    <p content-type="asset">
      <table-wrap id="t3">
        <graphic xlink:href="1678-4170-abc-91-04-0267-00010-gt03.jpg"/></table-wrap>
    </p>
    <p content-type="asset">
      <table-wrap id="t4">
        <graphic xlink:href="1678-4170-abc-91-04-0267-00010-gt04.jpg"/></table-wrap>
    </p>
    <p>
      <bold>Desempenho do teste de respira&#231;&#227;o lenta</bold>
    </p>
    <p>A <xref ref-type="table" rid="tab5">tabela 5</xref> sumariza o desempenho do TRL para os dois crit&#233;rios. Foram calculados sensibilidade, especificidade, valores preditivos, raz&#245;es de probabilidade e teste de Kappa para an&#225;lise de reprodutibilidade interobservadores, com os respectivos intervalos de confian&#231;a (m&#233;todo de Wilson).</p>
    <table-wrap id="tab5">
      <graphic xlink:href="1678-4170-abc-91-04-0267-00010-gt05.jpg"/></table-wrap>
    <p>O <xref ref-type="fig" rid="g1">gr&#225;fico 1</xref> representa a melhora da <italic>performance</italic> do TRL em rela&#231;&#227;o &#224; sensibilidade, especificidade e valores preditivos quando utilizamos um ponto de corte id&#234;ntico ao usado no diagn&#243;stico cl&#237;nico (140/90 mmHg no crit&#233;rio de normaliza&#231;&#227;o da PA).</p>
    <fig id="g1">
      <graphic xlink:href="1678-4170-abc-91-04-0267-00010-gf02.jpg"/></fig>
    <p>
      <bold>Discuss&#227;o</bold>
    </p>
    <p>O TRL revelou sensibilidade de 75% e especificidade de 81% para o crit&#233;rio de normaliza&#231;&#227;o da PA na identifica&#231;&#227;o da HAB, em duas consultas, quando da avalia&#231;&#227;o de pacientes hipertensos n&#227;o-medicados, sem les&#245;es de &#243;rg&#227;os-alvo e sem co-morbidades importantes. A raz&#227;o de probabilidade positiva obtida pelo teste aponta para um aumento na chance da presen&#231;a de HAB em at&#233; quatro vezes. Esses resultados sugerem que esse &#233; um teste simples, facilmente realiz&#225;vel pelo cl&#237;nico em seu consult&#243;rio, com possibilidade de aumentar consideravelmente a suspeita desse diagn&#243;stico.</p>
    <p>Realizamos an&#225;lise de concord&#226;ncia entre dois observadores e encontramos um teste de Kappa de 0,42 para o crit&#233;rio de normaliza&#231;&#227;o da PA, plenamente aceit&#225;vel para uma manobra cl&#237;nica em um cen&#225;rio de grande variabilidade.</p>
    <p>As varia&#231;&#245;es da press&#227;o arterial representam um problema para o diagn&#243;stico e o controle da hipertens&#227;o. A queda espont&#226;nea da PA pr&#233;-teste entre as consultas 1 e 2 (<xref ref-type="table" rid="tab1">tab. 1</xref>) confirma a necessidade de que sejam realizadas pelo menos duas consultas ap&#243;s a triagem para atenua&#231;&#227;o da rea&#231;&#227;o de alerta do paciente em ambiente m&#233;dico<sup>18,19</sup>. Por meio desse procedimento, encontramos nove pacientes normotensos (9% da amostra inicial), todos eles tomando previamente medica&#231;&#227;o anti-hipertensiva. Por sua vez, a HAB parece ser uma resposta condicionada que n&#227;o desaparece com o tempo<sup>20</sup> e cujo diagn&#243;stico depende do n&#237;vel de suspeita do m&#233;dico. O presente estudo sugere que o TRL &#233; mais efetivo na forma proposta aqui do que aquela usada por Yoshihara e cols.<sup>13</sup>. Esses autores realizaram o teste somente na primeira de tr&#234;s consultas e observaram melhor diferencia&#231;&#227;o com o crit&#233;rio de percentagem de queda da PA diast&#243;lica. Em nosso estudo, o teste foi aplicado em duas consultas ap&#243;s triagem, quando o efeito de habitua&#231;&#227;o que ocorreu com a repeti&#231;&#227;o das consultas contribuiu para aumentar o efeito da respira&#231;&#227;o lenta. Essa &#233; uma prov&#225;vel causa da queda mais intensa da PA sist&#243;lica p&#243;s-teste na segunda consulta em rela&#231;&#227;o &#224; primeira, para ambos os grupos HAB e HT (<xref ref-type="table" rid="tab1">tab. 1</xref>). Al&#233;m disso, o crit&#233;rio de normaliza&#231;&#227;o da PA &#233; facilmente interpretado pelo m&#233;dico. O crit&#233;rio 1 foi retirado ap&#243;s revis&#227;o da literatura<sup>13</sup>. J&#225; o crit&#233;rio 2 foi decorrente de nossa observa&#231;&#227;o.</p>
    <p>Tamb&#233;m avaliamos dois outros crit&#233;rios alternativos: queda da PA diast&#243;lica <underline>&gt;</underline> 5% e queda da PA sist&#243;lica <underline>&gt;</underline> 10%. Obtivemos para esses crit&#233;rios sensibilidade de 68% e 54% e especificidade de 36% e 55% para esses pontos de corte, respectivamente.</p>
    <p>A preval&#234;ncia da HAB &#233; inversamente proporcional &#224; gravidade da hipertens&#227;o no consult&#243;rio<sup>21</sup>. As respostas ao TRL de acordo com os est&#225;gios de hipertens&#227;o (<xref ref-type="table" rid="t4">tab. 4</xref> e <xref ref-type="table" rid="tab5">5</xref>), indicaram que os resultados utilizando o crit&#233;rio 2 (<xref ref-type="table" rid="tab5">tab. 5</xref>) respeitaram os mesmos determinantes para a MAPA no diagn&#243;stico da HAB: quanto menor o est&#225;gio da hipertens&#227;o cl&#237;nica, maior a chance de positividade para a HAB ao aplicar o TRL.</p>
    <p>O maior n&#250;mero de mulheres na casu&#237;stica reflete a freq&#252;&#234;ncia dos usu&#225;rios do Setor (mulheres 7:3 homens). Esse fato n&#227;o nos surpreende, pois no Brasil as mulheres procuram mais os servi&#231;os de sa&#250;de do que os homens<sup>22</sup>. &#201; de grande import&#226;ncia o diagn&#243;stico da HAB em mulheres, j&#225; que elas s&#227;o mais suscet&#237;veis a esta condi&#231;&#227;o<sup>21</sup>, tendo sido encontrada em 35% delas e em 20% dos homens em nossa casu&#237;stica.</p>
    <p>A queda da PA ap&#243;s o teste foi mais intensa no grupo HAB do que no HT, nas duas consultas (<xref ref-type="table" rid="tab1">tab. 1</xref>). Pode-se questionar se esses resultados seriam influenciados por alguma poss&#237;vel diferen&#231;a fisiol&#243;gica nos mecanismos de mudan&#231;a r&#225;pida da PA existente entre hipertensos e aqueles com HAB. Em rela&#231;&#227;o a isso, um estudo<sup>23</sup> utilizando MAPA direta (intra-arterial) em indiv&#237;duos com hipertens&#227;o cl&#237;nica detectou maior sensibilidade barorreflexa naqueles com menores m&#233;dias ambulatoriais quando comparados com aqueles que tinham maiores m&#233;dias. Nenhuma diferen&#231;a significativa na PA media de consult&#243;rio foi observada entre os grupos. Conforme visto antes, a respira&#231;&#227;o lenta aumenta a sensibilidade barorreflexa e diminui a PA em hipertensos<sup>11</sup>. Seria esse est&#237;mulo mais efetivo em diminuir n&#237;veis elevados da PA em indiv&#237;duos com uma melhor sensibilidade desse reflexo? Outros estudos ser&#227;o necess&#225;rios para investigar poss&#237;veis diferen&#231;as fisiol&#243;gicas.</p>
    <p>
      <bold>Limita&#231;&#245;es</bold>
    </p>
    <p>N&#227;o determinamos a reprodutibilidade do TRL nos mesmos indiv&#237;duos no decorrer do tempo. Foi levada em considera&#231;&#227;o recomenda&#231;&#227;o do Comit&#234; de &#201;tica, que considerou a viabilidade de manter hipertensos previamente tratados (agora ap&#243;s a MAPA) sem medica&#231;&#227;o por mais tempo. A suspens&#227;o da medica&#231;&#227;o teve efeito ansiog&#234;nico sobre alguns pacientes, o que demandou suporte telef&#244;nico no per&#237;odo de abstin&#234;ncia (tivemos duas consultas telef&#244;nicas e uma paciente retirou-se do estudo no per&#237;odo). Finalmente, seria desej&#225;vel aumentar a amostra com pacientes rec&#233;m-diagnosticados e n&#227;o medicados.</p>
    <p>
      <bold>Conclus&#227;o</bold>
    </p>
    <p>No presente estudo, o TRL mostrou aumento da suspeita cl&#237;nica de HAB em duas consultas ao utilizar o crit&#233;rio de normaliza&#231;&#227;o da PA. Isso sugere que esse teste simples e facilmente aplic&#225;vel pode auxiliar na otimiza&#231;&#227;o dos pedidos de MAPA para os casos suspeitos.</p>
    <p>
      <bold>Potencial conflito de interesses</bold>
    </p>
    <p>Declaro n&#227;o haver conflitos de interesses pertinentes.</p>
    <p>
      <bold>Fontes de financiamento</bold>
    </p>
    <p>Este estudo foi financiado pela Funda&#231;&#227;o de Aux&#237;lio &#224; Pesquisa do Estado de S&#227;o Paulo (FAPESP).</p>
    <p>
      <bold>Vincula&#231;&#227;o acad&#234;mica</bold>
    </p>
    <p>Este artigo &#233; parte de tese de Doutorado de Jos&#233; Marcos Thalenberg pela Universidade Federal de S&#227;o Paulo.</p>
    <p>
      <fn id="back" fn-type="corresp">
        <label>
          <bold>Correspond&#234;ncia:</bold>
        </label>
        <p> Jos&#233; Marcos Thalenberg </p>
        <p> R. Harmonia 564 ap. 171, Vila Madalena </p>
        <p> 05435-000, S&#227;o Paulo, SP - Brasil </p>
        <p> E-mail: </p>
        <p>
          <email xlink:href="jmthal@ajato.com.br">jmthal@ajato.com.br</email>
        </p>
      </fn>
    </p>
    <p>Artigo enviado em 08/12/2007; revisado recebido em 04/02/2008; aceito em 26/02/2008.</p>
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  <sub-article article-type="translation" id="TRen" xml:lang="en">
    <front-stub>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Original Articles</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title xml:lang="en">Slow breathing test increases the suspicion of white-coat hypertension in the office</article-title>
      </title-group>
      <abstract xml:lang="en">
        <p>BACKGROUND: It would be useful to have a clinical test that increases the suspicion of white coat hypertension (WCH) during the medical consultation. OBJECTIVE: To evaluate the Slow Breathing Test (SBT) when differentiating hypertension from WCH. METHODS: 101 hypertensive patients selected at triage had their medication withdrawn for 2-3 weeks. The blood pressure (BP) was measured before and after the SBT at two consultations at the office. The test consisted in breathing for 1 minute at the frequency of one respiratory cycle every 10 seconds. Two diagnostic criteria were compared: 1 - decrease in diastolic BP &gt;10% in at least one visit or 2- decrease in BP to normal levels (&lt;140/90 mm Hg) in at least one visit. The ambulatory blood pressure monitoring (ABPM) was performed while blinded to the clinical measurements. RESULTS: 71 women and 30 men, with a mean age of 51+10 years, with mean pre and post-test BP of 152+17/ 99+11 and 140+18/ 91+11 mm Hg were assessed. Nine patients had normal clinical and ambulatory measurements. Of the 92 patients, 28 (30%) were classified as having WCH; 15 had a positive test for Criterion 1 and 21 for the Criterion 2. Among 64 (70%) hypertensive individuals, 14 tested positive for Criterion 1 and 12 for Criterion 2. Sensitivity and specificity (95% CI): 0.54 (0.36-0.71) and 0.78 (0.67-0.87) for Criterion 1; 0.75 (0.57-0.87) and 0.81 (0.70-0.89) for Criterion 2. CONCLUSION: The SBT showed an increase in the clinical suspicion of WCH in two visits when using the BP normalization criterion. This finding suggests that the test can help in the optimization of ABPM requests for suspected cases.</p>
      </abstract>
      <kwd-group xml:lang="en">
        <kwd>Hypertension</kwd>
        <kwd>respiratory function tests</kwd>
        <kwd>blood pressure monitoring</kwd>
        <kwd>ambulatory</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <p>
        <bold>ORIGINAL ARTICLE</bold>
      </p>
      <p>
        <fn id="top-body2">
          <label>
            <bold>Slow breathing test increases the suspicion of White-coat hypertension in the office </bold>
          </label>
          <p>
            <bold>Jos&#233; Marcos Thalenberg; Rui Manoel dos Santos P&#243;voa; Maria Teresa Nogueira Bombig; Gustavo Andr&#233; Costa de S&#225;; &#193;lvaro Nagib Atallah; Br&#225;ulio Luna Filho</bold>
          </p>
        </fn>
      </p>
      <p>Universidade Federal de S&#227;o Paulo, S&#227;o Paulo, SP - Brazil</p>
      <p>Mailing Address</p>
      <p>
        <bold>SUMMARY</bold>
      </p>
      <p><bold>BACKGROUND:</bold> It would be useful to have a clinical test that increases the suspicion of white coat hypertension (WCH) during the medical consultation.</p>
      <p><bold>OBJECTIVE:</bold> To evaluate the Slow Breathing Test (SBT) when differentiating hypertension from WCH.</p>
      <p><bold>METHODS:</bold> 101 hypertensive patients selected at triage had their medication withdrawn for 2-3 weeks. The blood pressure (BP) was measured before and after the SBT at two consultations at the office. The test consisted in breathing for 1 minute at the frequency of one respiratory cycle every 10 seconds. Two diagnostic criteria were compared: 1 - decrease in diastolic BP <underline>&gt;</underline>10% in at least one visit or 2- decrease in BP to normal levels (&lt;140/90 mm Hg) in at least one visit. The ambulatory blood pressure monitoring (ABPM) was performed while blinded to the clinical measurements.</p>
      <p><bold>RESULTS:</bold> 71 women and 30 men, with a mean age of 51<underline>+</underline>10 years, with mean pre and post-test BP of 152<underline>+</underline>17/ 99<underline>+</underline>11 and 140<underline>+</underline>18/ 91<underline>+</underline>11 mm Hg were assessed. Nine patients had normal clinical and ambulatory measurements. Of the 92 patients, 28 (30%) were classified as having WCH; 15 had a positive test for Criterion 1 and 21 for the Criterion 2. Among 64 (70%) hypertensive individuals, 14 tested positive for Criterion 1 and 12 for Criterion 2. Sensitivity and specificity (95% CI): 0.54 (0.36-0.71) and 0.78 (0.67-0.87) for Criterion 1; 0.75 (0.57-0.87) and 0.81 (0.70-0.89) for Criterion 2.</p>
      <p><bold>CONCLUSIONS:</bold> The SBT showed an increase in the clinical suspicion of WCH in two visits when using the BP normalization criterion. This finding suggests that the test can help in the optimization of ABPM requests for suspected cases.</p>
      <p><bold>Key words:</bold> Hypertension / diagnosis; respiratory function tests; blood pressure monitoring, ambulatory.</p>
      <p>
        <bold>Introduction</bold>
      </p>
      <p>White coat hypertension (WCH), the most commonly used designation of isolated office hypertension, is defined as the presence of persistently elevated blood pressure (BP) in the medical environment and normal readings outside of it<sup>1</sup>. It affects 15 to 30% of the presumable hypertensive individuals<sup>2</sup>. This condition can lead to an unnecessary drug treatment, with consequences for patients and health systems<sup>3</sup>. On the other hand, WCH must be considered a pre-hypertensive state<sup>4,5</sup> and not an innocent state<sup>6,7</sup>, which needs a more intense follow-up. Diagnosis of WCH requires preferentially, the use of ambulatory blood pressure monitoring (ABPM)<sup>8</sup>. However, since the lack of clinical features is characteristic of WCH, this factor restricts the requisition of ABPM as a diagnostic tool<sup>9</sup>.</p>
      <p>Slow breathing, at a frequency of 0.1 Hz (6 respiratory cycles per minute, 1 cycle every 10 seconds), showed to be effective in increasing blood oxygenation, exercise tolerance and baroreflex sensitivity<sup>10,11</sup> and decreasing BP in hypertensive individuals<sup>11</sup>. It is presumed that this frequency promotes the synchronization between breathing and innate cardiovascular rhythms (Mayer waves, a 10-second rhythm in humans), with a consequent modulation of the central and peripheral (baroreflex)<sup>12</sup> autonomic activities. At a frequency of 5 cycles per minute, slow breathing produced a small difference in the decrease of diastolic BP between hypertensive individuals and those with WCH, when applied on a single visit<sup>13</sup>.</p>
      <p>The aim of the present study was to improve the use of the Slow Breathing Test (SBT), which could increase the suspicion of WCH at the office and consequently, optimize the requests for ABPM for the suspected cases.</p>
      <p>
        <bold>Methods</bold>
      </p>
      <p>
        <bold>Study design and patients</bold>
      </p>
      <p>In this cross-sectional accuracy study, 101 patients referred to the Service of Hypertensive Cardiology of the Federal University of Sao Paulo (Unifesp), between March 2003 and March 2005, were assessed through an initial triage. The assessment consisted of a structured questionnaire and interpretation of laboratory and electrocardiogram results, which are part of the routine assessment of the Service.</p>
      <p>The questionnaire included: when was hypertension diagnosed, anti-hypertensive medication used (name and dose), other medications being used, smoking and drinking habits, other diseases, hospital admissions (including hypertensive emergency/urgency treatment). At triage, inclusion criteria were: adult patients (age <underline>&gt;</underline> 18 years) with systolic BP (SBP) <underline>&gt;</underline>140 and &lt;180 mmHg or diastolic BP (DBP) <underline>&gt;</underline>90 and &lt;110 mmHg or those using anti-hypertensive medication and BP &lt;180/110 mmHg. Exclusion criteria were: patients with a history of treatment for hypertensive crises of any origin, secondary hypertension, diabetes mellitus, atrial fibrillation, unstable angina or angina of recent onset, valvulopathies with functional class &gt; 1, moderate to severe chronic obstructive pulmonary disease, serum creatinine <underline>&gt;</underline>1.5 mg/dl, Body Mass Index <underline>&gt;</underline>35, presence of Sokolow-Lyon index (SV 1, + R V 5/V 6 <underline>&gt;</underline>35 mm) at the ECG and alcoholism. All patients gave their free and informed consent to participate in the study and the study protocol was approved by the Ethics Committee in Research of Unifesp.</p>
      <p>
        <bold>Slow breathing test and BP measurements</bold>
      </p>
      <p>The selected patients were assessed 2 to 3 weeks after the withdrawal of anti-hypertensive medication<sup>14</sup>. The auscultatory measurement of BP (Korotkoff sounds I and V) was obtained through a mercury sphygmomanometer (Wan Med, S&#227;o Paulo, Brazil) with a 2 mm graduation and cuffs that were adequate to the circumference of the arm. With the patients in the sitting position, the BP was measured in both arms and the arm with the highest BP was chosen. After two minutes, a new measurement in the same arm was performed. In case of differences in DBP &gt; 5 mmHg, the procedure was repeated until a measurement with a lower difference was obtained. With the cuff positioned on the chosen arm, the patient was submitted to the slow breathing test (SBT), which consisted in inducing slow breathing for a minute at the frequency of 0.1 Hz (one respiratory cycle every 10 seconds). The patient was instructed by the doctor to simulate the respiratory pattern based on an analog clock placed on the table. Immediately after that, a single BP measurement was carried out in the previously chosen arm. The pulse frequency was estimated by a 30-second counting, by the radial pulse, immediately after the pre- and post-test measurements.</p>
      <p>Subsequently, a monitor was installed to perform the 24-hour ABPM (Dyna-MAPA, Cardios Sistemas, S&#227;o Paulo, Brazil; equivalent to Mobil-O-Graph, I.E.M., Stolberg, Germany) with an appropriate cuff placed on the non-dominant arm and programmed to measure BP every 15 minutes (while awake) and 30 minutes (during sleep). The sleeping and awake times were established individually and checked with the diary entries. On the following day, after the monitor removal, the same previously described procedures were performed to measure BP before and after the SBT at a new visit. The interpretation of the ABPM results was carried out while blinded to the clinical measurements and according to the Brazilian guidelines<sup>15</sup>. Patients with at least 50 readings while awake were included in the analysis.</p>
      <p>
        <bold>Reproducibility</bold>
      </p>
      <p>Interobserver reproducibility was verified based on the measurements obtained separately by a second physician who tested 20 patients twice, immediately after the consultations carried out by the first observer. Each doctor performed the assessment in isolation and no observer was allowed during the procedure to prevent the patient's BP elevation<sup>16</sup>. All the clinical measurements were obtained in the morning between 11 AM and 12 PM.</p>
      <p>
        <bold>Diagnostic criteria</bold>
      </p>
      <p>We considered as WCH the existence of office measurements <underline>&gt;</underline>140 mmHg (SBP) or <underline>&gt;</underline>90 mm Hg (DBP) at the two visits (also at the triage if the patient was not taking medication) and ABPM mean while awake &lt;135 mm Hg (SBP) and &lt;85 mm Hg (DBP).</p>
      <p>Two criteria were compared as a positive response to the SBT for the diagnosis of WCH. <bold>Criterion 1</bold>: decrease in DBP <underline>&gt;</underline>10% in at least one of the visits. <bold>Criterion 2</bold>: decrease in BP to normal levels, i.e., SBP &lt;140 and DBP &lt;90mmHg in at least one of the two visits.</p>
      <p>
        <bold>Statistical analysis</bold>
      </p>
      <p>Considering a mean prevalence of 20% of WCH, alpha error of 5% and statistical power of the sample of 90%, we estimated as necessary to have 92 individuals with a presumable diagnosis of sustained hypertension. The results were expressed as means and standard deviations (SD). The paired Student's <italic>t</italic> test and the Chi-square test were used to analyze the results. The performance of the SBT was evaluated by the determination of sensitivity, specificity, predictive values and likelihood ratio, with the respective 95% confidence intervals. To evaluate the interobserver reproducibility of the SBT, Kappa test was used. The statistical analyses were carried out with the programs Microsoft Excel and Confidence Interval Analysis, version 2.</p>
      <p><xref ref-type="fig" rid="en_10f1-body2">Figure 1</xref> summarizes the present study method:</p>
      <p content-type="asset">
        <fig id="en_10f1-body2">
          <graphic xlink:href="1678-4170-abc-91-04-0267-00010-gf01-en.jpg"/></fig>
      </p>
      <p>
        <bold>Results</bold>
      </p>
      <p>
        <bold>Some characteristics of the sample</bold>
      </p>
      <p>The sample consisted of 71 women and 30 men, with a mean age of 51&#177;10 years. Of the 101 patients, 57 were Caucasians, 40 were Black and 4 were Asians. Ten patients were aged e&#149; 65 years (7 women). Ninety-four patients used anti-hypertensive medication. Of these, 17 used monotherapy, 74 used 2 medications and 3 patients used 3 medications (the latter used suboptimal doses). The drugs used belonged to the following categories: thiazide diuretics, betablockers,dihydropiridinic calcium channel blockers and angiotensin-converting enzyme inhibitors (ACEI).</p>
      <p>
        <bold>Classification after the ABPM</bold>
      </p>
      <p>The pre- and post-test BP means were 152&#177;17 / 99&#177;11 and 140&#177;18 / 91&#177;11 mm Hg, respectively.</p>
      <p>Nine patients presented normal clinical and ambulatory measurements after medication withdrawal. Of the remaining 92, 28 (30%) were classified as having WCH (35% of the women and 20% of the men) and 64 (70%) as hypertensive (HT).</p>
      <p><xref ref-type="table" rid="tab1-body2">Table 1</xref> shows the BP means (&#177;SD) at the first and second visits before and after the SBT was applied and the ABPM means (&#177;SD) while awake in relation to the WCH and HT groups. As expected, the pre-test means in the WCH group were lower than those in the HT group.</p>
      <table-wrap id="tab1-body2">
        <graphic xlink:href="1678-4170-abc-91-04-0267-00010-gt01-en.jpg"/></table-wrap>
      <p>
        <graphic xlink:href="1678-4170-abc-91-04-0267-00010-e01-en.jpg"/></p>
      <p>A spontaneous pre-test decrease in BP was observed between visits 1 and 2 in both groups. A significant decrease in systolic and diastolic BP after the test in both groups was also observed.</p>
      <p>The highest decrease was observed at visit 2 in the WCH group; the lowest decrease was observed at visit 1 in the HT group. There was no significant difference between the pre- and post-test means of pulse frequency for both groups.</p>
      <p>For the WCH group and according to criterion 1, 8 patients were identified at visit 1 and 7 at visit 2; 4 patients responded positively to the SBT at the two visits. Regarding criterion 2, 12 patients were identified at visit 1 and 9 at visit 2; 9 patients responded positively to the SBT at both visits.</p>
      <p>Positive responses to both criteria were observed in 12 patients and 5 were not identified by either of the criteria.</p>
      <p><xref ref-type="table" rid="en_10t3-body2">Tables 3</xref> and <xref ref-type="table" rid="en_10t4-body2">4</xref> show the responses to the SBT (positive or negative) by criteria 1 and 2, according to the stages of hypertension defined by the V Brazilian Guidelines<sup>17</sup> and by the measurements registered at visit 2. In the WCH group, 25 individuals had clinical measurements compatible with stage 1 arterial hypertension; the other 3, with stage 2. In the HT group, 35 individuals had clinical measurements compatible with stage 1 arterial hypertension, 24 with stage 2 and 5 with stage 3.</p>
      <p content-type="asset">
        <table-wrap id="en_10t3-body2">
          <graphic xlink:href="1678-4170-abc-91-04-0267-00010-gt02-en.jpg"/></table-wrap>
      </p>
      <p content-type="asset">
        <table-wrap id="en_10t4-body2">
          <graphic xlink:href="1678-4170-abc-91-04-0267-00010-gt03-en.jpg"/></table-wrap>
      </p>
      <p>For the patients with BP compatible with stage 1, there was a significant difference between HT and WCH in response to the test for the criterion 2 (p&lt;0.003), but not for criterion 1 (p&lt;0.26).</p>
      <p>
        <bold>Slow breathing test performance</bold>
      </p>
      <p><xref ref-type="table" rid="tab5-body2">Table 5</xref> summarizes the SBT performance for the two criteria. The sensitivity, specificity, predictive values, likelihood ratios and Kappa test for the analysis of interobserver reproducibility were calculated, with the respective confidence intervals (Wilson's method).</p>
      <table-wrap id="tab5-body2">
        <graphic xlink:href="1678-4170-abc-91-04-0267-00010-gt04-en.jpg"/></table-wrap>
      <p><xref ref-type="fig" rid="gra1-body2">Graph 1</xref> shows the improvement in the performance of the SBT in terms of sensitivity, specificity and predictive values when the same cut-off value used in the clinical diagnosis (140/90 mm Hg for criterion 2) was applied.</p>
      <fig id="gra1-body2">
        <graphic xlink:href="1678-4170-abc-91-04-0267-00010-gf02-en.jpg"/></fig>
      <p>
        <bold>Discussion</bold>
      </p>
      <p>The SBT showed sensitivity of 75% and specificity of 81% for the BP normalization criterion in the identification of WCH in two visits, when non-medicated hypertensive patients, with no target-organ damages and no important comorbidities were assessed. The positive likelihood ratio obtained by the test points to an up to four-fold increase in the chance of WCH. These results suggest that this is a simple, easy-to-apply test by the clinician at the office, which allows a considerable increase in the suspicion of this diagnosis.</p>
      <p>We performed a concordance analysis between two observers and found a Kappa test of 0.42 for the BP normalization criterion, completely acceptable for a clinical maneuver in a situation that presents great variability.</p>
      <p>The variations in BP represent a problem for the diagnosis and control of hypertension. The spontaneous pre-test decrease in BP between visits 1 and 2 (<xref ref-type="table" rid="tab1-body2">Table 1</xref>) confirms the necessity of having at least 2 visits after triage to attenuate the patient's alert reaction to a medical environment<sup>18,19</sup>. Through this procedure, we found 9 normotensive patients (9% of the initial sample) all of them previously taking antihypertensive drugs. On the other hand, WCH seems to be a conditioned response that does not disappear with time<sup>20</sup> and of which diagnosis depends on the level of the suspicion by the physician.</p>
      <p>The present study suggests that the SBT is more effective as proposed here than as proposed by Yoshihara et al<sup>13</sup>. These authors reported better differentiation of the test effect between the groups when using the percentage decrease in diastolic BP on the first of three visits. In our study, the test was performed on two visits after triage, when the habituation effect that occurs along the repetition of the visits may enhance the effect of slow breathing. This is a probable cause of the more intense decrease in post-test systolic BP on the second visit in comparison to the first, for both WCH and HT groups (<xref ref-type="table" rid="tab1-body2">Table 1</xref>).</p>
      <p>Additionally, the criterion of BP normalization is easily interpreted by the physician. These criteria were derived from the literature (criterion 1)<sup>13</sup> and from our own observation (criterion 2).</p>
      <p>We also evaluated two other alternative criteria: decrease in diastolic BP <underline>&gt;</underline>5% and decrease in systolic BP <underline>&gt;</underline>10%. For these criteria, we obtained sensitivity of 68% and 54% and specificity of 36% and 55% for these cutoffs, respectively.</p>
      <p>The prevalence of WCH is inversely proportional to the severity of hypertension in the office<sup>21</sup>. The responses to the SBT according to the stages of hypertension (<xref ref-type="table" rid="en_10t4-body2">Tables 4</xref> and <xref ref-type="table" rid="tab5-body2">5</xref>) indicated that the results using the criterion 2 (<xref ref-type="table" rid="tab5-body2">Table 5</xref>) respected the same determinants for the ABPM in the diagnosis of WCH: the lower the stage of clinical hypertension, the higher the chance of positivity for WCH when applying the SBT.</p>
      <p>The larger number of women in our series reflects the frequency of users in this Service (7 women: 3 men). This fact is not surprising, as it is known in Brazil that women seek health services more often than men<sup>22</sup>. It is very important to attain the diagnosis of WCH in women, as they are more susceptible to this condition<sup>21</sup>. WCH was found in 35% of the women and 20% of the men in our series.</p>
      <p>The BP decrease after the test was more marked in the WCH group when compared to the HT group, in both consultations (<xref ref-type="table" rid="tab1-body2">Table 1</xref>). One can question whether these results could be influenced by any possible physiological difference in the mechanisms of rapid BP change between hypertensive individuals and those with WCH. Concerning that, a study<sup>23</sup> using direct ABPM (intra-arterial) in individuals with clinical hypertension detected higher baroreflex sensitivity in those with lower ambulatory means when compared to those that had higher means. No significant difference in the mean BP at the office was observed between the groups.</p>
      <p>As previously observed, slow breathing increases baroreflex sensitivity and decreases BP in hypertensive individuals<sup>11</sup>. Would this stimulus be more effective in decreasing elevated BP levels in individuals with a higher sensitivity of this reflex? Further studies will be necessary to investigate possible physiological differences.</p>
      <p>
        <bold>Limitations</bold>
      </p>
      <p>We did not determine the reproducibility of the SBT in the same individuals throughout time. We took into consideration the recommendation made by the Ethics Committee, which considered the viability of maintaining previously treated hypertensive individuals (now after ABPM) without medication for longer. Medication withdrawal had an ansiogenic effect on some patients, which required support by telephone during the withdrawal period (we had two telephone consultations and one patient withdrew from the study during the period). Finally, it would be advantageous to increase the sample with newly-diagnosed and medication-na&#239;ve patients.</p>
      <p>
        <bold>Conclusion</bold>
      </p>
      <p>The present study showed that the SBT increased the clinical suspicion of WCH in two visits when using the BP normalization criterion. This suggests that this simple and easy-to-apply test can help in the optimization of requests for ABPM for the suspected cases.</p>
      <p>
        <bold>Potential Conflict of Interest</bold>
      </p>
      <p>No potential conflict of interest relevant to this article was reported.</p>
      <p>
        <bold>Sources of Funding</bold>
      </p>
      <p>This study was funded by Funda&#231;&#227;o de Aux&#237;lio &#224; Pesquisa do Estado de S&#227;o Paulo (FAPESP).</p>
      <p>
        <bold>Study Association</bold>
      </p>
      <p>This article is part of the Doctoral thesis submitted by Jos&#233; Marcos Thalenberg, from Universidade Federal de S&#227;o Paulo.</p>
      <p>
        <bold>References</bold>
      </p>
    </body>
  </sub-article>
</article>
