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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">6jnJfMPR8QnqdmgtrCwvHXg</article-id>
      <article-id pub-id-type="other">00005</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v2">S0066-782X2008000600005</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v1">S0066-782X(08)09000605</article-id>
      <article-id pub-id-type="doi">10.1590/S0066-782X2008000600005</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Artigos Originais</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Recupera&#231;&#227;o da freq&#252;&#234;ncia card&#237;aca ap&#243;s teste de esfor&#231;o em esteira ergom&#233;trica e variabilidade da freq&#252;&#234;ncia card&#237;aca em 24 horas em indiv&#237;duos sadios</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Antelmi</surname>
            <given-names>Ivana</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Chuang</surname>
            <given-names>Eliseu Yung</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Grupi</surname>
            <given-names>Cesar Jos&#233;</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Latorre</surname>
            <given-names>Maria do Ros&#225;rio Dias de Oliveira</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Mansur</surname>
            <given-names>Alfredo Jos&#233;</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 de S&#227;o Paulo</institution>
        <institution content-type="orgdiv1">Faculdade de Medicina </institution>
        <institution content-type="orgdiv2">Instituto do Cora&#231;&#227;o</institution>
        <country country="BR">Brazil</country>
      </aff>
      <pub-date date-type="collection" publication-format="electronic">
        <month>06</month>
        <year>2008</year>
      </pub-date>
      <volume>90</volume>
      <issue>6</issue>
      <fpage>413</fpage>
      <lpage>418</lpage>
      <history>
        <date date-type="accepted">
          <day>21</day>
          <month>11</month>
          <year>2007</year>
        </date>
        <date date-type="rev-recd">
          <day>21</day>
          <month>09</month>
          <year>2007</year>
        </date>
        <date date-type="received">
          <day>28</day>
          <month>07</month>
          <year>2007</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: A recupera&#231;&#227;o da freq&#252;&#234;ncia card&#237;aca ap&#243;s o eletrocardiograma de esfor&#231;o em esteira ergom&#233;trica &#233; modulada pelo sistema nervoso aut&#244;nomo. A an&#225;lise da variabilidade da freq&#252;&#234;ncia card&#237;aca (VFC) pode fornecer informa&#231;&#245;es valiosas sobre o controle do sistema nervoso aut&#244;nomo sobre o sistema cardiovascular. OBJETIVO: O objetivo deste estudo foi testar a hip&#243;tese de associa&#231;&#227;o entre a recupera&#231;&#227;o da freq&#252;&#234;ncia card&#237;aca ap&#243;s teste de esfor&#231;o em esteira ergom&#233;trica e a variabilidade da freq&#252;&#234;ncia card&#237;aca. M&#201;TODOS: Foram estudamos 485 indiv&#237;duos sem evid&#234;ncia de cardiopatia com m&#233;dia de idade de 42&#177; 12,1 (faixa et&#225;ria de 15 a 82) anos, 281 (57.9%) dos quais do sexo feminino, submetidos a um teste de esfor&#231;o em esteira ergom&#233;trica e avalia&#231;&#227;o da VFC nos dom&#237;nios do tempo (SDNN, SDANN, SDNNi, rMSSD e pNN50) e da freq&#252;&#234;ncia (LF, HF, VLF e raz&#227;o LF/HF) durante monitoramento eletrocardiogr&#225;fico ambulatorial de 24 horas. RESULTADOS: A recupera&#231;&#227;o da freq&#252;&#234;ncia card&#237;aca foi de 30 &#177; 12 batimentos no 1&#186; minuto e 52&#177; 13 batimentos no 2&#186; minuto ap&#243;s o exerc&#237;cio. Os indiv&#237;duos mais jovens de recuperaram mais r&#225;pido do 2&#186; ao 5&#186; minuto ap&#243;s o exerc&#237;cio (r = 0,19-0,35, P &lt; 0,05). As mulheres se recuperaram mais r&#225;pido que os homens (4 &#177; 1,1 batimentos a menos no 1&#186; minuto, p &lt; 0,001; 5,7 &#177; 1,2 batimentos a menos no 2&#186; minuto, p &lt; 0,01; e 4,1&#177; 1,1 batimentos a menos no 3&#186; minuto, p &lt; 0.001). N&#227;o houve correla&#231;&#227;o significante entre a recupera&#231;&#227;o da freq&#252;&#234;ncia card&#237;aca e a VFC no 1&#186; e 2&#186; minutos ap&#243;s o exerc&#237;cio. Os &#237;ndices SDNN, SDANN, SDNNi, rMSSD e pNN50 s&#243; apresentaram uma correla&#231;&#227;o significante com a recupera&#231;&#227;o da freq&#252;&#234;ncia card&#237;aca no 3&#186; e 4&#186; minutos. CONCLUS&#195;O: A hip&#243;tese de associa&#231;&#227;o entre recupera&#231;&#227;o da freq&#252;&#234;ncia card&#237;aca e VFC em 24 horas nos primeiros dois minutos ap&#243;s o exerc&#237;cio n&#227;o foi comprovada neste estudo. A recupera&#231;&#227;o da freq&#252;&#234;ncia card&#237;aca foi associada com idade e sexo.</p>
      </abstract>
      <kwd-group xml:lang="pt" kwd-group-type="author-generated">
        <kwd>Freq&#252;&#234;ncia card&#237;aca</kwd>
        <kwd>recupera&#231;&#227;o da freq&#252;&#234;ncia card&#237;aca</kwd>
        <kwd>exerc&#237;cio</kwd>
        <kwd>teste de esfor&#231;o</kwd>
      </kwd-group>
      <pub-date publication-format="electronic" date-type="pub">
        <day>25</day>
        <month>06</month>
        <year>2008</year>
      </pub-date>
    </article-meta>
  </front>
  <body>
    <p>ARTIGO ORIGINAL </p>
    <p> ERGOMETRIA</p>
    <p>Recupera&#231;&#227;o da freq&#252;&#234;ncia card&#237;aca ap&#243;s teste de esfor&#231;o em esteira ergom&#233;trica e variabilidade da freq&#252;&#234;ncia card&#237;aca em 24 horas em indiv&#237;duos sadios</p>
    <p>
      <bold>Heart rate recovery after treadmill electrocardiographic exercise stress test and 24-hour heart rate variability in healthy individuals</bold>
    </p>
    <p>
      <bold>Ivana Antelmi; Eliseu Yung Chuang; Cesar Jos&#233; Grupi; Maria do Ros&#225;rio Dias de Oliveira Latorre; Alfredo Jos&#233; Mansur</bold>
    </p>
    <p>Instituto do Cora&#231;&#227;o - Faculdade de Medicina da Universidade de S&#227;o Paulo, S&#227;o Paulo, SP - Brasil</p>
    <p>
      <xref ref-type="corresp" rid="end">Correspond&#234;ncia</xref>
    </p>
    <p>
      <bold>RESUMO</bold>
    </p>
    <p><bold>FUNDAMENTO:</bold> A recupera&#231;&#227;o da freq&#252;&#234;ncia card&#237;aca ap&#243;s o eletrocardiograma de esfor&#231;o em esteira ergom&#233;trica &#233; modulada pelo sistema nervoso aut&#244;nomo. A an&#225;lise da variabilidade da freq&#252;&#234;ncia card&#237;aca (VFC) pode fornecer informa&#231;&#245;es valiosas sobre o controle do sistema nervoso aut&#244;nomo sobre o sistema cardiovascular. </p>
    <p><bold>OBJETIVO:</bold> O objetivo deste estudo foi testar a hip&#243;tese de associa&#231;&#227;o entre a recupera&#231;&#227;o da freq&#252;&#234;ncia card&#237;aca ap&#243;s teste de esfor&#231;o em esteira ergom&#233;trica e a variabilidade da freq&#252;&#234;ncia card&#237;aca. </p>
    <p><bold>M&#201;TODOS:</bold> Foram estudamos 485 indiv&#237;duos sem evid&#234;ncia de cardiopatia com m&#233;dia de idade de 42&#177; 12,1 (faixa et&#225;ria de 15 a 82) anos, 281 (57.9%) dos quais do sexo feminino, submetidos a um teste de esfor&#231;o em esteira ergom&#233;trica e avalia&#231;&#227;o da VFC nos dom&#237;nios do tempo (SDNN, SDANN, SDNNi, rMSSD e pNN50) e da freq&#252;&#234;ncia (LF, HF, VLF e raz&#227;o LF/HF) durante monitoramento eletrocardiogr&#225;fico ambulatorial de 24 horas. </p>
    <p><bold>RESULTADOS:</bold> A recupera&#231;&#227;o da freq&#252;&#234;ncia card&#237;aca foi de 30 &#177; 12 batimentos no 1&#186; minuto e 52&#177; 13 batimentos no 2&#186; minuto ap&#243;s o exerc&#237;cio. Os indiv&#237;duos mais jovens de recuperaram mais r&#225;pido do 2&#186; ao 5&#186; minuto ap&#243;s o exerc&#237;cio (r = 0,19-0,35, <italic>P</italic> &lt; 0,05). As mulheres se recuperaram mais r&#225;pido que os homens (4 &#177; 1,1 batimentos a menos no 1&#186; minuto, <italic>p</italic> &lt; 0,001; 5,7 &#177; 1,2 batimentos a menos no 2&#186; minuto, <italic>p</italic> &lt; 0,01; e 4,1&#177; 1,1 batimentos a menos no 3&#186; minuto, <italic>p</italic> &lt; 0.001). N&#227;o houve correla&#231;&#227;o significante entre a recupera&#231;&#227;o da freq&#252;&#234;ncia card&#237;aca e a VFC no 1&#186; e 2&#186; minutos ap&#243;s o exerc&#237;cio. Os &#237;ndices SDNN, SDANN, SDNNi, rMSSD e pNN50 s&#243; apresentaram uma correla&#231;&#227;o significante com a recupera&#231;&#227;o da freq&#252;&#234;ncia card&#237;aca no 3&#186; e 4&#186; minutos. </p>
    <p><bold>CONCLUS&#195;O:</bold> A hip&#243;tese de associa&#231;&#227;o entre recupera&#231;&#227;o da freq&#252;&#234;ncia card&#237;aca e VFC em 24 horas nos primeiros dois minutos ap&#243;s o exerc&#237;cio n&#227;o foi comprovada neste estudo. A recupera&#231;&#227;o da freq&#252;&#234;ncia card&#237;aca foi associada com idade e sexo. </p>
    <p><bold>Palavras-chave:</bold> Freq&#252;&#234;ncia card&#237;aca, recupera&#231;&#227;o da freq&#252;&#234;ncia card&#237;aca, exerc&#237;cio, teste de esfor&#231;o.</p>
    <p>
      <bold>SUMMARY</bold>
    </p>
    <p><bold>BACKGROUND: </bold>Heart rate recovery after treadmill electrocardiographic exercise stress test is modulated by the autonomic nervous system. Analysis of heart rate variability can provide useful information about autonomic control of the cardiovascular system. </p>
    <p><bold>OBJECTIVE: </bold>The aim of the study was to test the hypothesis of association between heart recovery after treadmill electrocardiographic exercise test and heart rate variability. </p>
    <p><bold>METHODS: </bold>We studied 485 healthy individuals aged 42&#177; 12.1 (range 15-82) years, 281(57.9%) women, submitted to treadmill electrocardiographic exercise stress tests and heart rate variability evaluations over time (SDNN, SDANN, SDNNi, rMSSD, pNN50) and frequency (LF, HF, VLF, LF/HF ratio) domains in 24-hour ambulatory electrocardiographic monitoring. </p>
    <p><bold>RESULTS: </bold>Heart rate recovery was 30&#177; 12 beats in the 1<sup>st</sup> minute and 52&#177; 13 beats in the 2<sup>nd</sup> minute after exercise. Younger individuals recovered faster from the 2<sup>nd</sup> to the 5<sup>th</sup> minute after exercise (r= 0.19-0.35, P&lt; 0.05). Recovery was faster in women than in men (4&#177; 1.1 beats lower in the 1<sup>st</sup> minute, p&lt;0.001; 5.7&#177; 1.2 beats lower in the 2<sup>nd</sup> minute, p&lt;0.01; 4.1&#177; 1.1 beats lower in the 3<sup>rd</sup> minute, p&lt;0.001). There was no significant correlation between heart rate recovery and heart rate variability in 1<sup>st</sup> and 2<sup>nd</sup> minutes after exercise. SDNN, SDANN, SDNNi, rMSSD, and pNN50 indices demonstrated a significant correlation with heart rate recovery only at the 3<sup>rd</sup> and 4<sup>th</sup> minutes. </p>
    <p><bold>CONCLUSION: </bold>The hypothesis of association between heart rate recovery and 24-hour heart rate variability in the first two minutes after exercise was not substantiated in this study. Heart rate recovery after exercise was associated with age and gender. </p>
    <p><bold>Key words: </bold>Heart rate, variability; exercise; exercise test.</p>
    <p>
      <bold>Introdu&#231;&#227;o</bold>
    </p>
    <p>Estudos recentes demonstraram que a diminui&#231;&#227;o da recupera&#231;&#227;o da freq&#252;&#234;ncia card&#237;aca (FC) ap&#243;s o exerc&#237;cio est&#225; associada com progn&#243;stico menos favor&#225;vel no acompanhamento dos pacientes. Em um estudo realizado entre setembro de 1990 e dezembro de 1993 com 2.428 indiv&#237;duos adultos encaminhados ap&#243;s um primeiro teste ergom&#233;trico limitado pelos sintomas e a tomografia computadorizada por emiss&#227;o de f&#243;ton &#250;nico (SPECT) associada &#224; cintilografia com t&#225;lio, uma redu&#231;&#227;o de 12 batimentos ou menos no 1&#186;minuto de recupera&#231;&#227;o em rela&#231;&#227;o &#224; FC no pico de exerc&#237;cio foi associada com maior mortalidade dos pacientes no acompanhamento (risco relativo ajustado igual a 2; intervalo de confian&#231;a de 95% 1,5 a 2,7; <italic>p</italic> &lt; 0,001)<sup>1</sup>. Em outro estudo, que avaliou 9.454 pacientes consecutivos encaminhados para teste de esfor&#231;o em esteira ergom&#233;trica, a recupera&#231;&#227;o da freq&#252;&#234;ncia card&#237;aca &lt; 12 batimentos por minuto no 1&#186; minuto ap&#243;s o exerc&#237;cio foi associada com maior mortalidade dos pacientes no acompanhamento (5% vs. 1%; coeficiente de risco 4,26; intervalo de confian&#231;a de 95% 2,65-6,68; <italic>P</italic> &lt; 0,001)<sup>2</sup>. Em outro estudo, ainda, realizado com 2.193 pacientes encaminhados para teste esfor&#231;o em esteira ergom&#233;trica para avalia&#231;&#227;o de dor tor&#225;cica, uma recupera&#231;&#227;o da freq&#252;&#234;ncia card&#237;aca inferior a 22 batimentos por minuto no 2&#186; minuto ap&#243;s o exerc&#237;cio foi significantemente associada com maior mortalidade (coeficiente de risco 2,6; intervalo de confian&#231;a de 95% 2,4-2,8; <italic>P</italic> &lt; 0,05)<sup>3</sup>.</p>
    <p>As amostras desses estudos eram compostas por pacientes encaminhados para teste de esfor&#231;o em esteira ergom&#233;trica por indica&#231;&#245;es cl&#237;nicas<sup>1-3,</sup> inclusive pacientes encaminhados para coronariografia<sup>1-3</sup>. Existem alguns relatos recentes de padr&#245;es de recupera&#231;&#227;o da freq&#252;&#234;ncia card&#237;aca ap&#243;s o exerc&#237;cio em pacientes sem qualquer evid&#234;ncia de cardiopatia ap&#243;s exame cl&#237;nico minucioso.</p>
    <p>A recupera&#231;&#227;o da freq&#252;&#234;ncia card&#237;aca imediatamente ap&#243;s o exerc&#237;cio &#233; considerada uma fun&#231;&#227;o da reativa&#231;&#227;o na modula&#231;&#227;o da atividade parassimp&#225;tica e uma redu&#231;&#227;o na modula&#231;&#227;o da atividade simp&#225;tica que costuma ocorrer durante os primeiros 30 segundos ap&#243;s o exerc&#237;cio<sup>4</sup>. Anormalidades na modula&#231;&#227;o da atividade parassimp&#225;tica foram apontadas como uma poss&#237;vel liga&#231;&#227;o fisiopatol&#243;gica com a associa&#231;&#227;o entre diminui&#231;&#227;o da freq&#252;&#234;ncia card&#237;aca na recupera&#231;&#227;o ap&#243;s o teste de esfor&#231;o em esteira ergom&#233;trica e maior mortalidade dos pacientes no per&#237;odo de acompanhamento<sup>2</sup>. Por esse motivo, nesses casos &#233; preciso estudar a fisiologia do sistema nervoso aut&#244;nomo.</p>
    <p>A variabilidade da freq&#252;&#234;ncia card&#237;aca (VFC) no dom&#237;nio do tempo e da freq&#252;&#234;ncia &#233; um valioso instrumento n&#227;o-invasivo para a avalia&#231;&#227;o da fisiologia do sistema nervoso aut&#244;nomo<sup>5</sup>. A an&#225;lise da VFC no dom&#237;nio do tempo &#233; feita por meio de &#237;ndices desenvolvidos por m&#233;todos estat&#237;sticos para a varia&#231;&#227;o das diferen&#231;as entre intervalos RR sucessivos. A an&#225;lise da VFC no dom&#237;nio da freq&#252;&#234;ncia &#233; feita por meio de an&#225;lise espectral, estando o componente de alta freq&#252;&#234;ncia (HF) relacionado com respira&#231;&#227;o. O componente de alta freq&#252;&#234;ncia (HF) &#233; mediado, sobretudo, pela atividade vagal, enquanto o componente de baixa freq&#252;&#234;ncia (LF) representa predominantemente a modula&#231;&#227;o simp&#225;tica<sup>6,7</sup>.</p>
    <p>Tivemos a oportunidade de avaliar uma amostra de indiv&#237;duos saud&#225;veis assintom&#225;ticos sem qualquer evid&#234;ncia de cardiopatia ap&#243;s exames cl&#237;nicos e laboratoriais minuciosos.</p>
    <p>Levantamos a hip&#243;tese de que diferentes taxas de recupera&#231;&#227;o da freq&#252;&#234;ncia card&#237;aca ap&#243;s teste de esfor&#231;o em esteira ergom&#233;trica estariam associadas com &#237;ndices distintos de variabilidade card&#237;aca em homens e mulheres saud&#225;veis de diversas idades como uma express&#227;o do equil&#237;brio entre a modula&#231;&#227;o simp&#225;tica e parassimp&#225;tica. Especificamente, testamos a hip&#243;tese de que indiv&#237;duos com &#237;ndices mais elevados de atividade parassimp&#225;tica teriam uma taxa mais alta de recupera&#231;&#227;o da freq&#252;&#234;ncia card&#237;aca ap&#243;s teste de esfor&#231;o em esteira ergom&#233;trica.</p>
    <p>O objetivo deste estudo foi avaliar a associa&#231;&#227;o entre os &#237;ndices de VFC, obtidos por meio de monitoriza&#231;&#227;o eletrocardiogr&#225;fica ambulatorial de 24 horas, e a recupera&#231;&#227;o da freq&#252;&#234;ncia card&#237;aca ap&#243;s teste ergom&#233;trico em esteira em uma grande amostra de indiv&#237;duos sem nenhuma evid&#234;ncia de cardiopatia ap&#243;s exames cl&#237;nicos e laboratoriais minuciosos.</p>
    <p>
      <bold>M&#233;todos</bold>
    </p>
    <p>
      <bold>Protocolo do estudo</bold>
    </p>
    <p>Uma coorte de indiv&#237;duos assintom&#225;ticos e sem evid&#234;ncia de cardiopatia ap&#243;s exames cl&#237;nicos e laboratoriais minuciosos foi estabelecida no Ambulat&#243;rio Geral de um hospital universit&#225;rio terci&#225;rio que tamb&#233;m presta atendimento prim&#225;rio e secund&#225;rio (exame cardiovascular, segundo parecer e avalia&#231;&#227;o card&#237;aca pr&#233;-operat&#243;ria) </p>
    <p>A avalia&#231;&#227;o incluiu exame cl&#237;nico detalhado, eletrocardiograma de 12 deriva&#231;&#245;es e radiografia do t&#243;rax. Os indiv&#237;duos assintom&#225;ticos, com exame cl&#237;nico, eletrocardiograma e radiografia de t&#243;rax normais, foram considerados eleg&#237;veis e convidados a participar do estudo. Depois de assinarem o termo de consentimento livre e esclarecido, os participantes foram submetidos a exames laboratoriais, teste de esfor&#231;o em esteira, ecocardiograma transtor&#225;cico bidimensional com Doppler e Holter de 24 horas. Os exames laboratoriais inclu&#237;ram glicemia de jejum, colesterol total, lipoprote&#237;na de alta densidade (HDL-colesterol), lipoprote&#237;na de baixa densidade (LDL-colesterol), triglic&#233;rides, &#225;cido &#250;rico, horm&#244;nio estimulador da tire&#243;ide (TSH) e creatinina. </p>
    <p>
      <bold>Crit&#233;rios de inclus&#227;o</bold>
    </p>
    <p>Foram inclu&#237;dos no estudo homens e mulheres assintom&#225;ticos com mais de 15 anos de idade que apresentaram exame cl&#237;nico, eletrocardiograma, radiografia do t&#243;rax, ecocardiograma e teste ergom&#233;trico normais. </p>
    <p>
      <bold>Crit&#233;rios de exclus&#227;o</bold>
    </p>
    <p>Foram exclu&#237;dos indiv&#237;duos com antecedente de doen&#231;a cardiovascular pr&#233;via, hipertens&#227;o sist&#234;mica, diabetes melito, TSH &lt; 0,05 ou &gt; 8 mg/dl, doen&#231;a pulmonar obstrutiva cr&#244;nica, insufici&#234;ncia renal, doen&#231;as inflamat&#243;rias cr&#244;nicas, doen&#231;as osteoarticulares, anemia cr&#244;nica ou neoplasia e resultados anormais no eletrocardiograma de 12 deriva&#231;&#245;es em repouso, ecocardiograma ou teste ergom&#233;trico. </p>
    <p>
      <bold>Amostra do estudo</bold>
    </p>
    <p>Quatrocentos e oitenta e cinco indiv&#237;duos entre 15 e 82 anos (m&#233;dia de 42 anos, desvio-padr&#227;o de 12) foram considerados aptos a participar do estudo, sendo 204 (42,1%) homens e 281 (57,9%) mulheres. As caracter&#237;sticas cl&#237;nicas, demogr&#225;ficas e laboratoriais da amostra do estudo s&#227;o apresentadas na <xref ref-type="table" rid="tab01">Tabela 1</xref>. </p>
    <table-wrap id="tab01">
      <graphic xlink:href="1678-4170-abc-90-06-0413-00005-gt01.jpg"/></table-wrap>
    <p>
      <bold>Teste ergom&#233;trico em esteira</bold>
    </p>
    <p>Os testes ergom&#233;tricos foram realizados no aparelho Fukuda Denshi MI 8000 Star de acordo com o protocolo de Bruce/Ellestad. A freq&#252;&#234;ncia card&#237;aca m&#225;xima prevista foi calculada por meio da f&#243;rmula 220 - idade. Os indiv&#237;duos foram estimulados a se exercitar at&#233; sentirem sintomas limitantes, mesmo que fosse atingida 85% da freq&#252;&#234;ncia card&#237;aca m&#225;xima prevista. O crit&#233;rio de interrup&#231;&#227;o do exerc&#237;cio era exaust&#227;o f&#237;sica ou freq&#252;&#234;ncia card&#237;aca m&#225;xima acima da esperada para a idade. Em cada est&#225;gio do exerc&#237;cio e da fase de recupera&#231;&#227;o eram registrados a press&#227;o arterial, a freq&#252;&#234;ncia card&#237;aca e o gasto energ&#233;tico em equivalentes metab&#243;licos (METS). Ap&#243;s o pico do exerc&#237;cio, os indiv&#237;duos caminhavam durante um per&#237;odo de desaquecimento de dois minutos a uma velocidade de 2,4 km/hora e grau de inclina&#231;&#227;o de 2,5%. A freq&#252;&#234;ncia card&#237;aca era medida a cada minuto de exerc&#237;cio, no pico do exerc&#237;cio e nos 1, 2, 3, 4 e 5 minutos da recupera&#231;&#227;o com o paciente em p&#233;. A recupera&#231;&#227;o da freq&#252;&#234;ncia card&#237;aca foi definida como a freq&#252;&#234;ncia card&#237;aca m&#225;xima atingida menos a freq&#252;&#234;ncia card&#237;aca em um per&#237;odo especificado na recupera&#231;&#227;o, e representava a queda da freq&#252;&#234;ncia card&#237;aca durante esse intervalo de tempo. Os testes ergom&#233;tricos foram realizados, analisados e relatados com base em um protocolo convencional com utiliza&#231;&#227;o de um banco de dados computadorizado. </p>
    <p>
      <bold>Variabilidade da freq&#252;&#234;ncia card&#237;aca</bold>
    </p>
    <p>Todos os indiv&#237;duos foram submetidos ao registro eletrocardiogr&#225;fico de 24 horas. O tempo m&#233;dio de grava&#231;&#227;o das fitas de Holter foi de 22,6 &#177; 1 hora. Todos os registros foram obtidos com gravadores port&#225;teis Marquette 8000 e processados pelo equipamento Marquette MARS 8000, com amostragem de 125 Hz, com emprego do programa MARS, vers&#227;o 4.0 (Milwaukee, Wisconsin). Cada batimento era classificado e rotulado com rela&#231;&#227;o ao local de origem por meio de t&#233;cnicas de compara&#231;&#227;o de padr&#245;es ("template-matching"). O programa elimina um intervalo RR antes e dois intervalos RR depois de cada batimento n&#227;o-sinusal. Um observador experiente revisava e corrigia manualmente todos os tra&#231;ados. Os registros cujos batimentos n&#227;o-sinusais representavam mais de 2% do n&#250;mero total de batimentos eram exclu&#237;dos. Algoritmos correspondentes fornecidos pelo fabricante foram usados na an&#225;lise da VFC. Os seguintes &#237;ndices de dom&#237;nio no tempo foram estudados: desvio-padr&#227;o de todos os intervalos RR normais durante 24 horas (SDNN); desvio-padr&#227;o das m&#233;dias dos intervalos RR normais em todos os segmentos de cinco minutos (SDANN); m&#233;dias dos desvios-padr&#227;o dos intervalos RR normais em todos os segmentos de cinco minutos (SDNNi); raiz quadrada m&#233;dia da diferen&#231;a entre os intervalos RR normais sucessivos (rMSSD); e porcentagem de intervalos RR normais sucessivos &gt; 50 ms (pNN50). No dom&#237;nio de freq&#252;&#234;ncia (Transformada r&#225;pida de Fourier), os seguintes &#237;ndices foram comparados: muito baixa freq&#252;&#234;ncia (VLF) de 0,0003 a 0,04 Hz, baixa freq&#252;&#234;ncia (LF) de 0,04 a 0,15 Hz, alta freq&#252;&#234;ncia (HF) de 0,15 a 0.40 Hz e raz&#227;o LF/HF.</p>
    <p>
      <bold>An&#225;lise estat&#237;stica</bold>
    </p>
    <p>Ap&#243;s an&#225;lise estat&#237;stica descritiva, a associa&#231;&#227;o entre recupera&#231;&#227;o da freq&#252;&#234;ncia card&#237;aca, idade, sexo e &#237;ndices de variabilidade da freq&#252;&#234;ncia card&#237;aca foi avaliada por meio da correla&#231;&#227;o de Pearson e de regress&#227;o linear m&#250;ltipla. Valores de p &lt; 0,05 foram considerados estatisticamente significantes.</p>
    <p>
      <bold>Aspectos de natureza &#233;tica</bold>
    </p>
    <p>O protocolo do estudo foi aprovado pela Comiss&#227;o de &#201;tica em Pesquisas com Seres Humanos do Hospital, e todos os indiv&#237;duos assinaram um termo de consentimento livre e esclarecido.</p>
    <p>
      <bold>Resultados</bold>
    </p>
    <p>
      <bold>Recupera&#231;&#227;o da freq&#252;&#234;ncia card&#237;aca</bold>
    </p>
    <p>A recupera&#231;&#227;o da freq&#252;&#234;ncia card&#237;aca ap&#243;s o exerc&#237;cio foi mais pronunciada nos dois primeiros minutos ap&#243;s o t&#233;rmino do esfor&#231;o. A m&#233;dia de redu&#231;&#227;o da freq&#252;&#234;ncia card&#237;aca foi de 30,8 (desvio-padr&#227;o de 12,1) batimentos no primeiro minuto e de 52 (desvio-padr&#227;o de 13,4) batimentos no segundo minuto. A <xref ref-type="table" rid="tab02">tabela 2</xref> apresenta a queda da freq&#252;&#234;ncia card&#237;aca nos primeiros 5 minutos da recupera&#231;&#227;o. A freq&#252;&#234;ncia card&#237;aca geralmente n&#227;o retornava aos n&#237;veis iniciais anteriores ao exerc&#237;cio ap&#243;s os 5 minutos da recupera&#231;&#227;o.</p>
    <table-wrap id="tab02">
      <graphic xlink:href="1678-4170-abc-90-06-0413-00005-gt02.jpg"/></table-wrap>
    <p>Os indiv&#237;duos que apresentaram maior aumento da freq&#252;&#234;ncia card&#237;aca durante o exerc&#237;cio mostraram uma taxa de recupera&#231;&#227;o mais r&#225;pida do segundo ao quinto minuto ap&#243;s o exerc&#237;cio (r = 0,16, 0,36, 0,48 <italic>P</italic> &lt; 0,05, no 2&#186;, 3&#186; e 4&#186; minutos, respectivamente). Essa rela&#231;&#227;o n&#227;o foi observada no primeiro minuto ap&#243;s o exerc&#237;cio, mesmo depois do ajuste por idade. A freq&#252;&#234;ncia card&#237;aca em repouso foi significantemente correlacionada com a recupera&#231;&#227;o da freq&#252;&#234;ncia card&#237;aca no 4&#186; e 5&#186; minutos ap&#243;s o exerc&#237;cio (r = 0,2, P &lt; 0,05).</p>
    <p>
      <bold>Recupera&#231;&#227;o da freq&#252;&#234;ncia card&#237;aca em rela&#231;&#227;o &#224; idade e ao sexo</bold>
    </p>
    <p>A recupera&#231;&#227;o da freq&#252;&#234;ncia card&#237;aca apresentou uma correla&#231;&#227;o estatisticamente significante com a idade. Os indiv&#237;duos mais novos apresentaram uma recupera&#231;&#227;o da freq&#252;&#234;ncia card&#237;aca mais r&#225;pida, quando comparados com os indiv&#237;duos mais velhos, observada do 2&#186; ao 5&#186; minutos ap&#243;s o exerc&#237;cio (r = 0,19-0,35 <italic>P</italic>&lt; 0,05). A recupera&#231;&#227;o da freq&#252;&#234;ncia card&#237;aca foi mais r&#225;pida nas mulheres do que nos homens: 4&#177; 1,1 (&lt; 0,05) batimentos no 1&#186; minuto, 5,7&#177; 1,2 (p&lt; 0,05) batimentos no 2&#186; minuto e 4,1&#177; 1,1 (p &lt; 0,05) batimentos no 3&#186; minuto. A diferen&#231;a na recupera&#231;&#227;o da freq&#252;&#234;ncia card&#237;aca entre homens e mulheres no 4&#186; minuto ap&#243;s o exerc&#237;cio n&#227;o foi estatisticamente significante (<xref ref-type="fig" rid="fig01">Figura 1</xref>).</p>
    <fig id="fig01">
      <graphic xlink:href="1678-4170-abc-90-06-0413-00005-gf01.jpg"/></fig>
    <p>
      <bold>Recupera&#231;&#227;o da freq&#252;&#234;ncia card&#237;aca em rela&#231;&#227;o &#224; variabilidade da freq&#252;&#234;ncia card&#237;aca</bold>
    </p>
    <p>N&#227;o houve associa&#231;&#227;o entre a recupera&#231;&#227;o da freq&#252;&#234;ncia card&#237;aca ap&#243;s o exerc&#237;cio e a variabilidade da freq&#252;&#234;ncia card&#237;aca observada no 1&#186; e 2&#186; minutos ap&#243;s o exerc&#237;cio, na an&#225;lise no dom&#237;nio do tempo e da freq&#252;&#234;ncia. </p>
    <p>Em rela&#231;&#227;o &#224; variabilidade da freq&#252;&#234;ncia card&#237;aca na an&#225;lise no dom&#237;nio do tempo, observou-se associa&#231;&#227;o entre recupera&#231;&#227;o da freq&#252;&#234;ncia card&#237;aca ap&#243;s o exerc&#237;cio e os &#237;ndices SDNN, SDANN, SDNNi, rMSSD, e pNN50 no 3&#186; e 4&#186; minutos ap&#243;s o exerc&#237;cio (<xref ref-type="table" rid="tab03">Tabela 3</xref>). As correla&#231;&#245;es n&#227;o foram estatisticamente significantes para o 5&#186; minuto de recupera&#231;&#227;o ap&#243;s o exerc&#237;cio.</p>
    <table-wrap id="tab03">
      <graphic xlink:href="1678-4170-abc-90-06-0413-00005-gt03.jpg"/></table-wrap>
    <p>Em rela&#231;&#227;o &#224; variabilidade da freq&#252;&#234;ncia card&#237;aca na an&#225;lise no dom&#237;nio da freq&#252;&#234;ncia, observou-se associa&#231;&#227;o entre recupera&#231;&#227;o da freq&#252;&#234;ncia card&#237;aca ap&#243;s o exerc&#237;cio e o &#237;ndice de muito baixa freq&#252;&#234;ncia (VLF) no 3&#186; e 4&#186; minutos ap&#243;s o exerc&#237;cio. N&#227;o houve correla&#231;&#227;o significante entre os &#237;ndices de alta freq&#252;&#234;ncia (HF) e raz&#227;o baixa freq&#252;&#234;ncia/alta freq&#252;&#234;ncia (LF/HF) em nenhum minuto da recupera&#231;&#227;o (<xref ref-type="table" rid="tab03">Tabela 3</xref>). A correla&#231;&#227;o mais forte entre recupera&#231;&#227;o da freq&#252;&#234;ncia card&#237;aca e variabilidade da freq&#252;&#234;ncia card&#237;aca foi observada no 4&#186; minuto de recupera&#231;&#227;o para os &#237;ndices de LF.</p>
    <p>Ap&#243;s o ajuste para a idade e sexo na an&#225;lise de regress&#227;o m&#250;ltipla, a correla&#231;&#227;o entre SDNN e recupera&#231;&#227;o da freq&#252;&#234;ncia card&#237;aca no 3&#186; e 4&#186; minutos ap&#243;s o exerc&#237;cio permaneceu estatisticamente significante.</p>
    <p>
      <bold>Discuss&#227;o</bold>
    </p>
    <p>Estudamos a recupera&#231;&#227;o da freq&#252;&#234;ncia card&#237;aca ap&#243;s o exerc&#237;cio em uma amostra composta por homens e mulheres sem evid&#234;ncia de cardiopatia ap&#243;s avalia&#231;&#227;o cl&#237;nica e laboratorial minuciosa. Essa &#233; uma caracter&#237;stica interessante da popula&#231;&#227;o deste estudo, uma vez que estudos anteriores inclu&#237;ram cardiopatas e n&#227;o-cardiopatas<sup>8,9</sup>, desde indiv&#237;duos normais at&#233; portadores de quadros patol&#243;gicos com v&#225;rios graus de gravidade. Outros estudos importantes inclu&#237;ram apenas homens<sup>10-12</sup>. Nossa amostra era constitu&#237;da por indiv&#237;duos sedent&#225;rios, n&#227;o-atletas, com consumo m&#225;ximo de oxig&#234;nio no teste de esfor&#231;o em esteira ergom&#233;trica inferior a 44,9 mL/kg/min<sup>13</sup>.</p>
    <p>Os valores m&#233;dios da recupera&#231;&#227;o da freq&#252;&#234;ncia card&#237;aca ap&#243;s o exerc&#237;cio foram mais elevados na nossa amostra, quando comparados a estudos pr&#233;vios publicados<sup>1-3</sup> que correlacionaram a recupera&#231;&#227;o da freq&#252;&#234;ncia card&#237;aca ap&#243;s esfor&#231;o a um progn&#243;stico cardiovascular. &#201; importante observar tamb&#233;m que, neste estudo, a taxa de redu&#231;&#227;o da freq&#252;&#234;ncia card&#237;aca ap&#243;s o exerc&#237;cio diferiu entre o sexo masculino e o sexo feminino, apresentando o sexo feminino uma redu&#231;&#227;o mais acentuada da freq&#252;&#234;ncia card&#237;aca nos primeiros 3 minutos da recupera&#231;&#227;o. Essa diferen&#231;a na redu&#231;&#227;o da freq&#252;&#234;ncia card&#237;aca em rela&#231;&#227;o ao sexo n&#227;o foi abordada em estudos anteriores realizados com homens e mulheres<sup>1,2</sup>. Esse achado pode estar relacionado com a sugest&#227;o anterior de maior modula&#231;&#227;o da atividade parassimp&#225;tica em mulheres do que em homens, de acordo com estudos sobre variabilidade da freq&#252;&#234;ncia card&#237;aca<sup>13-16</sup>. Al&#233;m disso, sabe-se que, durante o exerc&#237;cio, as mulheres t&#234;m menos condicionamento cardiorrespirat&#243;rio, maior d&#233;bito card&#237;aco com cargas compar&#225;veis e menor volume sist&#243;lico, o que faz com que o equil&#237;brio entre a demanda e a oferta de O<sub>2 , </sub>seja obtido por meio de um aumento na freq&#252;&#234;ncia card&#237;aca<sup>17-19</sup>. Demonstrou-se que a capacidade aer&#243;bica de mulheres sedent&#225;rias na fase da menopausa era inferior &#224; de homens na mesma faixa et&#225;ria<sup>20</sup>. Pode ser que essas bases fisiol&#243;gicas estivessem em a&#231;&#227;o nos nossos achados.</p>
    <p>A taxa de recupera&#231;&#227;o da freq&#252;&#234;ncia card&#237;aca ap&#243;s o exerc&#237;cio tamb&#233;m foi modulada pela idade, como constataram outros autores. A freq&#252;&#234;ncia card&#237;aca m&#225;xima e o d&#233;bito card&#237;aco foram mais baixos em indiv&#237;duos mais velhos, em parte por causa da menor resposta beta-adren&#233;rgica<sup>21</sup> e em parte por causa da menor carga de exerc&#237;cio atingida. Cinq&#252;enta por cento do aumento na freq&#252;&#234;ncia card&#237;aca pode ser atribu&#237;do &#224; estimula&#231;&#227;o simp&#225;tica, principalmente estimula&#231;&#227;o beta-adren&#233;rgica, e &#224;s catecolaminas circulantes. </p>
    <p>N&#227;o observamos uma rela&#231;&#227;o entre os &#237;ndices de variabilidade da freq&#252;&#234;ncia card&#237;aca em monitoriza&#231;&#227;o ambulatorial de 24 horas e a recupera&#231;&#227;o da freq&#252;&#234;ncia card&#237;aca nos dois primeiros minutos ap&#243;s o teste ergom&#233;trico em esteira, per&#237;odo no qual a atividade parassimp&#225;tica constitui o principal determinante da redu&#231;&#227;o dos batimentos card&#237;acos. Nossos dados mostraram que a recupera&#231;&#227;o da freq&#252;&#234;ncia card&#237;aca ap&#243;s o exerc&#237;cio n&#227;o estava relacionada com o componente de alta freq&#252;&#234;ncia (HF), que &#233; considerado um &#237;ndice predominantemente parassimp&#225;tico. Al&#233;m disso, &#237;ndices do dom&#237;nio do tempo modulados tamb&#233;m predominantemente por est&#237;mulos parassimp&#225;ticos, como rMMSD e pNN50, n&#227;o revelaram uma associa&#231;&#227;o com a recupera&#231;&#227;o da freq&#252;&#234;ncia card&#237;aca nos dois primeiros minutos, apenas a partir do 3&#186; e 4&#186; minutos ap&#243;s o exerc&#237;cio. Surpreendentemente, os &#237;ndices SDNN, SDANN e SDNNi, que sofrem influ&#234;ncias simp&#225;ticas e parassimp&#225;ticas, tamb&#233;m foram associados com a recupera&#231;&#227;o da freq&#252;&#234;ncia card&#237;aca no 3&#186; e 4&#186; minutos. Esse foi um achado inesperado, pois os &#237;ndices HF, rMMSD e o pNN50 s&#227;o mais influenciados pelo t&#244;nus vagal, como foi demonstrado em estudos controlados com atropina em registros de cinco minutos<sup>16</sup>. As condi&#231;&#245;es do registro de 24 horas da an&#225;lise da variabilidade da freq&#252;&#234;ncia card&#237;aca podem ter influenciado esse achado. Em um estudo recente realizado com 70 homens com mais de 70 anos de idade<sup>12</sup>, n&#227;o foi observada rela&#231;&#227;o significante entre a recupera&#231;&#227;o da freq&#252;&#234;ncia card&#237;aca e os &#237;ndices rMSSD, pNN50, HF e a raz&#227;o LF/HF, mas apenas com o &#237;ndice LH no primeiro minuto de recupera&#231;&#227;o ap&#243;s o exerc&#237;cio. </p>
    <p>Nosso estudo tem algumas limita&#231;&#245;es a serem consideradas. A recupera&#231;&#227;o da freq&#252;&#234;ncia card&#237;aca ap&#243;s o exerc&#237;cio foi avaliada durante um procedimento de desaquecimento "cool down" (primeiros dois minutos com velocidade de 2,4 km e grau de inclina&#231;&#227;o de 2,5%). N&#227;o se sabe ao certo o impacto exercido pelo tipo de protocolo e o per&#237;odo de desaquecimento sobre a recupera&#231;&#227;o da freq&#252;&#234;ncia card&#237;aca ap&#243;s o exerc&#237;cio, e ainda n&#227;o foram padronizados protocolos de recupera&#231;&#227;o na pr&#225;tica cl&#237;nica. Sem um protocolo de desaquecimento, as diferen&#231;as podem variar com a cessa&#231;&#227;o imediata do exerc&#237;cio e retomada da posi&#231;&#227;o ortost&#225;tica<sup>20</sup>. </p>
    <p>
      <bold>Conclus&#227;o</bold>
    </p>
    <p>Concluindo, a recupera&#231;&#227;o da freq&#252;&#234;ncia card&#237;aca ap&#243;s o exerc&#237;cio foi associada com a idade e o sexo. Indiv&#237;duos mais novos apresentaram uma recupera&#231;&#227;o da freq&#252;&#234;ncia card&#237;aca ap&#243;s o esfor&#231;o mais r&#225;pida observada entre o segundo e quinto minutos ap&#243;s o exerc&#237;cio, e a recupera&#231;&#227;o da freq&#252;&#234;ncia card&#237;aca tamb&#233;m foi mais r&#225;pida no sexo feminino. A hip&#243;tese de associa&#231;&#227;o entre recupera&#231;&#227;o da freq&#252;&#234;ncia card&#237;aca e os &#237;ndices de variabilidade da freq&#252;&#234;ncia card&#237;aca analisados em monitoriza&#231;&#227;o de 24 horas nos primeiros dois minutos ap&#243;s o exerc&#237;cio n&#227;o foi comprovada neste estudo. S&#243; houve associa&#231;&#227;o entre recupera&#231;&#227;o da freq&#252;&#234;ncia card&#237;aca e os &#237;ndices desvio-padr&#227;o de todos os intervalos RR normais durante 24 horas (SDNN); desvio-padr&#227;o das m&#233;dias dos intervalos RR em ritmo sinusal normal durante todos os segmentos de cinco minutos (SDANN); m&#233;dias dos desvio-padr&#227;o de todos os intervalos RR normais em todos os segmentos de cinco minutos (SDNNi); raiz quadrada m&#233;dia da diferen&#231;a entre os intervalos RR normais sucessivos (rMSSD); e porcentagem de intervalos RR normais sucessivos &gt;50 ms (pNN50) no 3&#186; e 4&#186; minutos ap&#243;s o exerc&#237;cio. </p>
    <p>Nossos dados contribuem para a an&#225;lise da recupera&#231;&#227;o da freq&#252;&#234;ncia card&#237;aca nos primeiros cinco minutos ap&#243;s o exerc&#237;cio em indiv&#237;duos sem evid&#234;ncia de cardiopatia ap&#243;s avalia&#231;&#227;o cl&#237;nica e laboratorial minuciosa. Esse achado pode ser valioso para futuros estudos nesta &#225;rea. </p>
    <p>
      <bold>Potencial Conflito de Interesses</bold>
    </p>
    <p>Declaro n&#227;o haver conflito de interesses pertinentes.</p>
    <p>
      <bold>Fontes de Financiamento</bold>
    </p>
    <p>O presente estudo n&#227;o teve fontes de financiamento externas.</p>
    <p>
      <bold>Vincula&#231;&#227;o Acad&#234;mica</bold>
    </p>
    <p>Este artigo &#233; parte de tese de doutorado de Ivana Antelmi pela Faculdade de Medicina da Universidade de S&#227;o Paulo.</p>
    <p>
      <fn id="end" fn-type="corresp">
        <label>
          <bold>Correspond&#234;ncia:</bold>
        </label>
        <p> Ivana Antelmi </p>
        <p> Rua Belgrado, 199 - Vila Moinho Velho </p>
        <p> 04285-040, S&#227;o Paulo, SP - Brasil </p>
        <p> E-mail: </p>
        <p>
          <email xlink:href="iantelmi@cardiol.br">iantelmi@cardiol.br</email>
        </p>
      </fn>
    </p>
    <p>Artigo recebido em 28/07/07; revisado recebido em 21/09/07; aceito em 21/11/07.</p>
  </body>
  <back>
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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">Heart rate recovery after treadmill electrocardiographic exercise stress test and 24-hour heart rate variability in healthy individuals</article-title>
      </title-group>
      <abstract xml:lang="en">
        <p>BACKGROUND: Heart rate recovery after treadmill electrocardiographic exercise stress test is modulated by the autonomic nervous system. Analysis of heart rate variability can provide useful information about autonomic control of the cardiovascular system. OBJECTIVE: The aim of the study was to test the hypothesis of association between heart recovery after treadmill electrocardiographic exercise test and heart rate variability. METHODS: We studied 485 healthy individuals aged 42&#177; 12.1 (range 15-82) years, 281(57.9%) women, submitted to treadmill electrocardiographic exercise stress tests and heart rate variability evaluations over time (SDNN, SDANN, SDNNi, rMSSD, pNN50) and frequency (LF, HF, VLF, LF/HF ratio) domains in 24-hour ambulatory electrocardiographic monitoring. RESULTS: Heart rate recovery was 30&#177; 12 beats in the 1st minute and 52&#177; 13 beats in the 2nd minute after exercise. Younger individuals recovered faster from the 2nd to the 5th minute after exercise (r= 0.19-0.35, P&lt; 0.05). Recovery was faster in women than in men (4&#177; 1.1 beats lower in the 1st minute, p&lt;0.001; 5.7&#177; 1.2 beats lower in the 2nd minute, p&lt;0.01; 4.1&#177; 1.1 beats lower in the 3rd minute, p&lt;0.001). There was no significant correlation between heart rate recovery and heart rate variability in 1st and 2nd minutes after exercise. SDNN, SDANN, SDNNi, rMSSD, and pNN50 indices demonstrated a significant correlation with heart rate recovery only at the 3rd and 4th minutes. CONCLUSION: The hypothesis of association between heart rate recovery and 24-hour heart rate variability in the first two minutes after exercise was not substantiated in this study. Heart rate recovery after exercise was associated with age and gender.</p>
      </abstract>
      <kwd-group xml:lang="en">
        <kwd>Heart rate, variability</kwd>
        <kwd>exercise</kwd>
        <kwd>exercise test</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <p>
        <bold>ORIGINAL ARTICLE</bold>
      </p>
      <p><undefined id="tx-body2"/>Heart rate recovery after treadmill electrocardiographic exercise stress test and 24-hour heart rate variability in healthy individuals</p>
      <p>
        <bold>Ivana Antelmi; Eliseu Yung Chuang; Cesar Jos&#233; Grupi; Maria do Ros&#225;rio Dias de Oliveira Latorre; Alfredo Jos&#233; Mansur</bold>
      </p>
      <p>Instituto do Cora&#231;&#227;o - Faculdade de Medicina da Universidade 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> Heart rate recovery after treadmill electrocardiographic exercise stress test is modulated by the autonomic nervous system. Analysis of heart rate variability can provide useful information about autonomic control of the cardiovascular system.</p>
      <p><bold>OBJECTIVE:</bold> The aim of the study was to test the hypothesis of association between heart recovery after treadmill electrocardiographic exercise test and heart rate variability.</p>
      <p><bold>METHODS:</bold> We studied 485 healthy individuals aged 42&#177; 12.1 (range 15-82) years, 281(57.9%) women, submitted to treadmill electrocardiographic exercise stress tests and heart rate variability evaluations over time (SDNN, SDANN, SDNNi, rMSSD, pNN50) and frequency (LF, HF, VLF, LF/HF ratio) domains in 24-hour ambulatory electrocardiographic monitoring.</p>
      <p><bold>RESULTS:</bold> Heart rate recovery was 30&#177; 12 beats in the 1<sup>st</sup> minute and 52&#177; 13 beats in the 2<sup>nd</sup> minute after exercise. Younger individuals recovered faster from the 2<sup>nd</sup> to the 5<sup>th</sup> minute after exercise (r= 0.19-0.35, P&lt; 0.05). Recovery was faster in women than in men (4&#177; 1.1 beats lower in the 1<sup>st</sup> minute, p&lt;0.001; 5.7&#177; 1.2 beats lower in the 2<sup>nd</sup> minute, p&lt;0.01; 4.1&#177; 1.1 beats lower in the 3<sup>rd</sup> minute, p&lt;0.001). There was no significant correlation between heart rate recovery and heart rate variability in 1<sup>st</sup> and 2<sup>nd</sup> minutes after exercise. SDNN, SDANN, SDNNi, rMSSD, and pNN50 indices demonstrated a significant correlation with heart rate recovery only at the 3<sup>rd</sup> and 4<sup>th</sup> minutes.</p>
      <p><bold>CONCLUSION:</bold> The hypothesis of association between heart rate recovery and 24-hour heart rate variability in the first two minutes after exercise was not substantiated in this study. Heart rate recovery after exercise was associated with age and gender.</p>
      <p><bold>Key words:</bold> Heart rate, variability; exercise; exercise test.</p>
      <p>
        <bold>Introduction</bold>
      </p>
      <p>Recent studies have demonstrated that impaired heart rate recovery after exercise was associated with less favorable prognosis in patient follow-up. In a study of 2,428 consecutive adults referred for a first symptom-limited electrocardiographic exercise stress test and single-photon emission computed tomography (SPECT) with thallium between September 1990 and December 1993, the decrease of 12 beats or less in the 1<sup>st</sup> minute of recovery relative to heart rate at peak exercise was associated with higher mortality rate during follow-up (adjusted relative risk 2; 95% confidence interval 1.5 &#150; 2.7; p &lt; 0.001)<sup>1</sup>. Another study examined 9,454 consecutive patients referred for treadmill electrocardiographic exercise stress test: heart rate recovery &lt;12 beats per minute in the 1<sup>st</sup> minute after exercise was associated with higher mortality during follow-up (5% <italic>vs</italic> 1%; hazard ratio 4.26; 95% confidence interval 2.65-6.68; P&lt;0.001)<sup>2</sup>. In an additional study of 2,193 patients referred for treadmill electrocardiographic exercise stress test for evaluation of chest pain, heart rate recovery lower than 22 beats per minute in the 2<sup>nd</sup> minute after exercise was significantly associated with higher mortality (hazard ratio 2.6; 95% confidence interval 2.4-2.8; p &lt; 0.05)<sup>3</sup>.</p>
      <p>Study samples in these reports consisted of patients referred for treadmill electrocardiographic exercise stress test due to clinical indications<sup>1-3</sup>, including patients referred for coronary angiography<sup>1,3</sup>. There are few recent reports of patterns of heart rate recovery after exercise in patients without any evidence of heart disease after careful clinical examination. </p>
      <p>Heart rate recovery immediately after exercise is considered to be a function of reactivation of the parasympathetic drive and a decrease in the sympathetic drive that usually occurs during the first 30 seconds of recovery after exercise<sup>4</sup>. Abnormalities in parasympathetic activation and drive were suggested as a potential pathophysiological link to the observed association between reduced or impaired heart rate in early recovery after treadmill electrocardiographic exercise stress test and increased mortality during the follow-up period<sup>2</sup>. Hence, the study of autonomic nervous system physiology in this setting may be warranted. </p>
      <p>Heart rate variability in time and frequency domains is a noninvasive tool useful for evaluation of autonomic nervous system physiology<sup>5</sup>. Time domain analysis of heart rate variability estimates the variation of differences between successive RR intervals through indices developed by statistical methods. Frequency domain analysis of heart rate variability estimates respiratory-dependent high frequency and low frequency power through spectral analysis. High frequency power is considered to be mediated mainly by vagal activity, while low frequency power has been suggested to represent predominantly sympathetic modulation<sup>6,7</sup>.</p>
      <p>We had the opportunity of evaluating a sample of asymptomatic healthy individuals without any evidence of heart disease after careful clinical and laboratory examination.</p>
      <p>We hypothesized that different rates of heart rate recovery after treadmill electrocardiographic exercise stress test would be associated with different indices of heart variability in healthy men and women of different ages as an expression of the balance between parasympathetic and sympathetic drives. Specifically, we tested the hypothesis that individuals with higher indices of parasympathetic activity would have higher rate of recovery of heart rate after treadmill electrocardiographic exercise stress test.</p>
      <p>The aim of this study was to evaluate the association between heart rate variability indices obtained during 24-hour ambulatory electrocardiographic monitoring and heart rate recovery after treadmill electrocardiographic exercise stress test in a large sample of subjects without any evidence of heart disease after careful clinical and laboratory examination.</p>
      <p>
        <bold>Methods</bold>
      </p>
      <p><italic>Study protocol</italic> - A cohort of asymptomatic individuals with no evidence of heart disease after careful clinical examination was established to evaluate clinical and cardiovascular variables. Patients were from a General Outpatient Clinic Unit of a tertiary care university hospital dedicated to cardiology that provides also primary and secondary care. </p>
      <p>Clinical evaluation included a detailed medical examination, 12-lead electrocardiogram and chest X-ray. The asymptomatic individuals with normal clinical examination, as well as normal electrocardiogram and chest X-ray, were considered eligible for the study, and were invited to participate. After informed and written consent, participants were submitted to further laboratory work-up, including treadmill electrocardiographic exercise stress test, two-dimensional transthoracic Doppler echocardiography, and 24-hour ambulatory electrocardiographic monitoring. In addition, laboratory work-up included hemoglobin, hematocrit, leukocyte count, serum glucose, serum cholesterol, triglycerides, uric acid, thyroid-stimulating hormone, and creatinine. </p>
      <p><italic>Inclusion criteria</italic> - We included in the study men and women older than 15 years of age, asymptomatic and with normal clinical examination, as well as normal electrocardiogram, chest X-ray, echocardiogram and treadmill electrocardiographic exercise stress test. </p>
      <p><italic>Exclusion criteria</italic> - We excluded symptomatic patients, as well as patients with past medical history of cardiovascular disease, systemic hypertension, diabetes mellitus, thyroid-stimulating hormone lower than 0.05 or higher than 8 mg/dl, chronic obstructive pulmonary disease, asthma, renal failure, chronic inflammatory diseases, osteoarticular diseases, chronic anemia or neoplasia, and abnormal 12-lead resting electrocardiogram, echocardiogram or treadmill electrocardiographic exercise stress test.</p>
      <p><italic>Study sample - </italic>485 individuals were enrolled in the study; 204 (42.1%) men and 281 (57.9%) women. Ages ranged between 15 and 82 (mean 42, standard deviation 12.1) years. Demographic, clinical and laboratory characteristics of the study sample are presented in <xref ref-type="table" rid="tab01-body2">Table 1</xref>. </p>
      <table-wrap id="tab01-body2">
        <graphic xlink:href="1678-4170-abc-90-06-0413-00005-gt01-en.jpg"/></table-wrap>
      <p><italic>Treadmill exercise stress test </italic>- Tests were performed on the Fukuda Denshi MI &#150; 8000 Star model according to the Bruce/Ellestad protocol. Predicted peak heart rate was calculated as 220 - age. Individuals were encouraged to exercise until they experienced limiting symptoms, even if 85% of maximum predicted heart rate was achieved. Criteria for exercise termination were physical exhaustion or maximum heart rate greater than the age-predicted maximum. During each exercise stage and recovery stage, symptoms, blood pressure, heart rate and exercise workload in metabolic equivalents (METS) were recorded. Following peak exercise, individuals walked for a two-minute cool-down period at 1.5 mph and 2.5% grade. Heart rate was measured during each minute of exercise, at maximum exercise, and during recovery at 1, 2, 3, 4 and 5 minutes in the standing position. Heart rate recovery was defined as maximum heart rate minus heart rate at specified time period after exercise and represented the drop in heart rate during that time interval. The exercise tests were performed, analyzed and reported with a standard protocol utilizing a computerized database. In this study, all tests were terminated due to exhaustion. </p>
      <p><italic>Heart rate variability</italic> - All subjects underwent 24-hour electrocardiographic recording. Mean recording time of Holter tapes was 22.6 &#177; 1 hour. All measurements were obtained with a Marquette 8000 portable recorder and processed by Marquette MARS 8000 equipment with 125-Hz sampling using MARS software version 4.0 (Milwaukee, Wisconsin). Each beat was classified and labeled with respect to the site of origin using template-matching techniques. The program eliminates 1 RR interval before and 2 after each non-sinus beat. An experienced observer manually reviewed and corrected all tracing. Recording with non-sinus beats that comprised &gt; 2% of the total number of beats were excluded. Corresponding algorithms supplied by the manufacturer were used to analyze HRV. The following time-domain indices were studied: Standard deviation (SD) of all normal sinus RR intervals during 24 hours (SDNN), SD of averaged normal sinus RR intervals for all 5-minute segments (SDANN), mean of the SDs of all normal sinus RR intervals for all 5-minute segments (SDNNi), and root-mean-square of the successive normal sinus RR interval difference (rMSSD), and percentage of successive normal sinus RR intervals &gt;50 ms (pNN50). In the frequency domain (fast-Fourier transform), the following indices were compared: very low frequency (VLF) of 0.0003 to 0.04 Hz, low frequency (LF) of 0.04 to 0.15 Hz, high frequency (HF) of 0.15 to 0.40 Hz, and the LF/HF ratio (LF/HF).</p>
      <p><italic>Statistical analysis</italic> - After descriptive statistics, the association between heart rate recovery, age, gender and heart rate variability indices was assessed with Pearson correlation and multiple linear regression models. A <italic>P</italic> value &lt;0.05 was considered significant.</p>
      <p><italic>Ethical aspects</italic> - The study protocol was approved by the Committee of Ethics on Human Research of the Hospital. Subjects who agreed to participate in the study signed an informed consent.</p>
      <p>
        <bold>Results</bold>
      </p>
      <p><italic>Heart rate recovery</italic> - Heart rate recovery after exercise was more pronounced in the first 2 minutes after exercise. Mean decrease in heart rate was 30.8 beats (standard deviation 12.1) in the first minute after exercise and 52 beats (standard deviation 13.4) in the second minute after exercise. Further data are presented in <xref ref-type="table" rid="tab02-body2">table 2</xref>. Heart rate usually did not return to pre-exercise levels within 5 minutes. </p>
      <table-wrap id="tab02-body2">
        <graphic xlink:href="1678-4170-abc-90-06-0413-00005-gt02-en.jpg"/></table-wrap>
      <p>Subjects with higher increase in heart rate during exercise demonstrated a faster recovery rate from the second to the fifth minute after exercise (r=0.16, 0.36, 0.48 P&lt;0.05, respectively 2<sup>nd</sup>, 3<sup>rd</sup> and 4<sup>th</sup> minutes); this relationship was not demonstrated in the first minute after exercise, even after controlling for age. Resting heart rate correlated significantly with heart rate recovery at the 4<sup>th</sup> and 5<sup>th</sup> minutes after exercise (r= 0.2, P&lt;0.05).</p>
      <p><italic>Heart rate recovery relative to age and gender</italic> - Heart rate recovery after exercise demonstrated a statistically significant correlation with age: younger individuals recovered faster than older ones from the second to the fifth minute after exercise (r= 0.19-0.35 P&lt;0.05). Heart rate recovery in women was more rapid than in men: the rate was 4&#177; 1.1 (&lt;0.05) beats more rapid at the first minute, 5.7&#177; 1.2 (p&lt;0.05) beats more rapid at the second minute, and 4.1&#177; 1.1 (p&lt;0.05) beats more rapid than in men at the third minute. The difference in heart rate recovery between men and women from the 4<sup>th</sup> minute after exercise was not statistically significant (<xref ref-type="fig" rid="fig01-body2">figure 1</xref>).</p>
      <fig id="fig01-body2">
        <graphic xlink:href="1678-4170-abc-90-06-0413-00005-gf01-en.jpg"/></fig>
      <p><italic>Heart rate recovery relative to heart rate variability</italic> - We found no association between heart rate recovery and heart rate variability for the 1<sup>st</sup> and 2<sup>nd</sup> minutes of recovery after exercise, neither in time nor in frequency domains. </p>
      <p>For heart rate variability indices in the time domain, there was an association between heart rate recovery and SDNN, SDANN, SDNNi, rMSSD, and pNN50 indices in the time domain of heart rate variability only at the 3<sup>rd</sup> and 4<sup>th</sup> minutes of recovery after exercise (<xref ref-type="table" rid="tab03-body2">table 3</xref>). Correlations were not more statistically significant for the 5<sup>th</sup> minute of recovery after exercise.</p>
      <table-wrap id="tab03-body2">
        <graphic xlink:href="1678-4170-abc-90-06-0413-00005-gt03-en.jpg"/></table-wrap>
      <p>For heart rate variability indices in the frequency domain, there was an association between heart rate recovery and very low frequency (VLF) in the frequency domain only at the 3<sup>rd</sup> and 4<sup>th</sup> minutes of recovery after exercise. We found no significant correlation between high frequency power (HF) and low frequency to high frequency power ratio (LF/HF) at any minute of recovery (<xref ref-type="table" rid="tab03-body2">table 3</xref>). The strongest correlation between heart rate recovery and heart rate variability was identified at 4<sup>th</sup> minute of recovery for LF indices. </p>
      <p>Correlation between SDNN and heart rate recovery after exercise at 3<sup>rd </sup>and 4<sup>th </sup>minutes remained statistically significant after controlling for age and gender in multiple regression analysis.</p>
      <p>
        <bold>Discussion</bold>
      </p>
      <p>We studied heart rate recovery after exercise in a sample of men and women without any evidence of heart disease after careful clinical and laboratory evaluation. This is an interesting characteristic of this study sample, since previous studies included subjects with and without heart disease<sup>8,9</sup> in a range from normal to several degrees of pathologic conditions. Other important studies included only men<sup>10-12</sup>. In addition, our sample was composed of non-athlete, sedentary subjects with maximal oxygen consumption below 44.9ml/kg/min<sup>13</sup> during treadmill exercise testing.</p>
      <p>In our sample, mean heart rate recovery was much higher than that associated with poor prognosis in published studies<sup>1-3</sup>. It is also noteworthy that, in this study, heart rate decrease after exercise was different in men and women; decrease being faster in women. This difference in the rate of decline relative to sex has not been addressed in previous studies that enrolled men and women<sup>1,2</sup>. This finding may be related to the previous suggestion of higher parasympathetic drive in women in comparison to men as found in studies of heart rate variability<sup>13-16</sup>. Additionally, during exercise women are usually considered to have lower cardiorespiratory fitness, higher cardiac outputs for comparable workloads and lower systolic volume, providing a balance between O<sub>2</sub> demand and supply from increased heart rate<sup>17-19</sup>. These physiological bases may have been operative in our findings. Sedentary women in menopause displayed lower aerobic capacity than men in the same age range<sup>20</sup>. To compensate for lower capacity, aerobic power in women during dynamic exercise increased more than in men.</p>
      <p>Recovery rate after exercise was also modulated by age as found by others. Maximum heart rate and cardiac output were lower in older individuals, partly because of decreased beta-adrenergic responsivity<sup>21</sup> and partly because of lower workload. Fifty percent of the increase in heart rate may be attributed to sympathetic stimulation, mainly beta-adrenergic stimulation and circulating catecholamines. </p>
      <p>There was no relationship between 24-hour heart rate variability indices in heart rate recovery in the first two minutes after the treadmill electrocardiographic exercise stress test, when parasympathetic activity is the major determinant of heart rate reduction. Our data showed that heart rate recovery after exercise was not related to the high frequency component in the frequency domain, which is considered an index of parasympathetic activity. In addition, indices modulated mainly by parasympathetic stimuli such as rMMSD and pNN50 in the time domain did reveal an association with heart rate recovery after exercise in the 3<sup>rd</sup> and 4<sup>th</sup> minutes. Surprisingly, SDNN, SDANN and SDNNi indices, which are an expression of both sympathetic and parasympathetic influences, were also associated with heart rate recovery in the 3<sup>rd</sup> and 4<sup>th</sup> minutes. This was an unexpected finding because high-frequency component, rMMSD and pNN50 are more influenced by the vagal tone, as demonstrated in controlled experiments with atropine in 5-minute recording<sup>16</sup>. The 24-hour recording conditions may also have modulated this finding. In a recent study of 70 men over 70 years of age<sup>12</sup>, no significant relationship between heart rate recovery and rMSSD, pNN50, high frequency component and low-frequency to high-frequency component ratio was detected, except in the low frequency component during the first minute of recovery after exercise.</p>
      <p>Our study has limitations. Heart rate recovery after exercise is modulated by a procedure of cool-down as was performed in this study (first 2 min of 1.5 mph at 2.5%). The impact of exercise protocol and cool-down period on heart rate recovery after exercise is uncertain, and recovery protocols have not yet been standardized in clinical practice. The mechanism of this modulated recovery is less well known. Differences might well vary with immediate cessation of exercise and assumption of the supine position without a cool-down protocol<sup>20</sup>.</p>
      <p>
        <bold>Conclusion</bold>
      </p>
      <p>In conclusion, heart rate recovery after exercise was associated with age and gender. Younger individuals recovered faster than older ones from the second to the fifth minute after exercise and heart rate recovery in women was more rapid than in men. The hypothesis of association between heart rate recovery and indices of 24-hour heart rate variability in the first two minutes after exercise was not substantiated in this study. There was an association between heart rate recovery and Standard deviation (SD) of all normal sinus RR intervals during 24 hours (SDNN), SD of averaged normal sinus RR intervals for all 5-minute segments (SDANN), mean SDs of all normal sinus RR intervals for all 5-minute segments (SDNNi), root-mean-square of the successive normal sinus RR interval difference (rMSSD), percentage of successive normal sinus RR intervals &gt;50 ms (pNN50) in the time domain only at the 3<sup>rd</sup> and 4<sup>th</sup> minutes of recovery after exercise. Our data may add to the evaluation of heart rate recovery in the first 5 minutes after exercise in subjects without any evidence heart disease after careful clinical and laboratory evaluation. Such a finding may be useful for further studies in the field. </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>There were no external funding sources for this study.</p>
      <p>
        <bold>Study Association</bold>
      </p>
      <p>This article is part of the thesis of doctoral submitted by Ivana Antelmi, from <italic>Faculdade de Medicina da Universidade de S&#227;o Paulo</italic>.</p>
      <p>
        <bold>References</bold>
      </p>
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