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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">49rch6xMJ7BcwLyd9vQq4SJ</article-id>
      <article-id pub-id-type="other">00036</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v2">S0066-782X2006001800036</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v1">S0066-782X(06)08700536</article-id>
      <article-id pub-id-type="doi">10.1590/S0066-782X2006001800036</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Atualiza&#231;&#227;o Cl&#237;nica</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>O papel do exerc&#237;cio aer&#243;bico sobre a fun&#231;&#227;o endotelial e sobre os fatores de risco cardiovasculares</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Sasaki</surname>
            <given-names>Jeffer Eidi</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Santos</surname>
            <given-names>Maria Gisele dos</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
      </contrib-group>
      <aff id="aff01">
        <addr-line>
          <named-content content-type="city">Curitiba</named-content>
          <named-content content-type="state">PR</named-content>
        </addr-line>
        <institution content-type="orgname">Universidade Federal do Paran&#225;</institution>
      </aff>
      <pub-date date-type="collection" publication-format="electronic">
        <month>11</month>
        <year>2006</year>
      </pub-date>
      <volume>87</volume>
      <issue>5</issue>
      <fpage>e226</fpage>
      <lpage>e231</lpage>
      <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>
      <pub-date publication-format="electronic" date-type="pub">
        <day>06</day>
        <month>03</month>
        <year>2007</year>
      </pub-date>
    </article-meta>
  </front>
  <body>
    <p>
      <bold>ATUALIZA&#199;&#195;O CL&#205;NICA</bold>
    </p>
    <p>
      <bold>O papel do exerc&#237;cio aer&#243;bico sobre a fun&#231;&#227;o endotelial e sobre os fatores de risco cardiovasculares</bold>
    </p>
    <p>
      <bold>Jeffer Eidi Sasaki; Maria Gisele dos Santos</bold>
    </p>
    <p> Universidade Federal do Paran&#225;, Curitiba, PR</p>
    <p>
      <xref ref-type="corresp" rid="back">Correspond&#234;ncia</xref>
    </p>
    <p><bold>Palavras-chave:</bold> Aterosclerose, exerc&#237;cio aer&#243;bico, fatores de risco.</p>
    <p>As doen&#231;as coronarianas, entre elas a aterosclerose, se tornaram a principal causa de morte na civiliza&#231;&#227;o moderna<sup>1,2</sup>. Esse problema &#233; decorrente de muitos aspectos do estilo de vida moderno, entre eles alimenta&#231;&#227;o irregular, tabagismo, ingest&#227;o de bebidas alco&#243;licas em excesso, estresse cotidiano, e principalmente o sedentarismo.</p>
    <p>Esses h&#225;bitos causam o desenvolvimento de fatores de risco relacionados &#224; aterosclerose. A forma&#231;&#227;o de placas ateroscler&#243;ticas ou ateromas est&#225; diretamente relacionada a acidentes coronarianos, como o infarto, a doen&#231;a isqu&#234;mica do cora&#231;&#227;o, e a apoplexia<sup>3</sup>.</p>
    <p>A detec&#231;&#227;o dos est&#225;gios prim&#225;rios da aterosclerose pode ser feita pela observa&#231;&#227;o de algumas altera&#231;&#245;es da parede arterial. Uma dessas altera&#231;&#245;es &#233; a diminui&#231;&#227;o da vasodilata&#231;&#227;o endot&#233;lio-dependente, relacionada com altos riscos de desenvolvimento ateroscler&#243;tico<sup>4</sup>. Outra altera&#231;&#227;o &#233; o espessamento das camadas m&#233;dia-&#237;ntima, um est&#225;gio prim&#225;rio da aterosclerose<sup>5,6</sup>, que pode ser monitorado nos indiv&#237;duos assintom&#225;ticos.</p>
    <p>Quando diagnosticadas tais modifica&#231;&#245;es, a preven&#231;&#227;o pode evitar a progress&#227;o aterog&#234;nica, restabelecendo assim a integridade arterial (<xref ref-type="fig" rid="figura1">fig. 1</xref>).</p>
    <fig id="figura1">
      <graphic xlink:href="1678-4170-abc-87-05-e226-00036-gf01.jpg"/></fig>
    <p>A rela&#231;&#227;o do exerc&#237;cio com a vasodilata&#231;&#227;o endot&#233;lio-dependente e com a espessura m&#233;dia-&#237;ntima tem sido estudada. No entanto, n&#227;o &#233; grande o n&#250;mero desse tipo de estudo. Ainda assim, os resultados t&#234;m sugerido que o exerc&#237;cio aer&#243;bico &#233; eficiente na melhoria desses &#237;ndices. Esse trabalho tem por objetivo contribuir com a discuss&#227;o atual mediante uma revis&#227;o de literatura.</p>
    <p>
      <bold>Exerc&#237;cio aer&#243;bico e aterosclerose</bold>
    </p>
    <p>Etimologicamente, a palavra aterosclerose vem do grego "<italic>athero</italic>" (papa, mingau) e "<italic>sclerosis</italic>" (endurecimento)<sup>2</sup>. A aterosclerose &#233; uma doen&#231;a cr&#244;nico-degenerativa caracterizada pelo estreitamento do l&#250;men arterial pela deposi&#231;&#227;o de gorduras e forma&#231;&#227;o de placas lipofibr&#243;ticas<sup>2,3,7</sup>.</p>
    <p>As altera&#231;&#245;es cardiovasculares s&#227;o amplamente relatadas na literatura, sendo as principais: aumento do volume do cora&#231;&#227;o, aumento do volume de eje&#231;&#227;o, aumento da concentra&#231;&#227;o de eritr&#243;citos e hemoglobina no sangue, diminui&#231;&#227;o da freq&#252;&#234;ncia card&#237;aca de repouso e da press&#227;o arterial, melhoria da vasculariza&#231;&#227;o perif&#233;rica, entre outros<sup>8-10</sup>.</p>
    <p>O exerc&#237;cio aer&#243;bico, no qual existe uma exig&#234;ncia predominante de oxig&#234;nio, propicia a queima oxidativa de subst&#226;ncias energ&#233;ticas, entre elas carboidratos, gorduras e prote&#237;nas. A propor&#231;&#227;o da utiliza&#231;&#227;o desses substratos &#233; dependente da intensidade do exerc&#237;cio<sup>8</sup>.</p>
    <p>Al&#233;m desses benef&#237;cios, pelo treinamento aer&#243;bico os pacientes ateroscler&#243;ticos podem apresentar melhorias da reatividade arterial e da espessura m&#233;dia-&#237;ntima. Estudos<sup>11</sup> t&#234;m demonstrado que a intensidade moderada, em conjunto com uma regularidade de treino, parece ser mais eficiente na promo&#231;&#227;o de benef&#237;cios &#224; fun&#231;&#227;o endotelial. Nos t&#243;picos seguintes, s&#227;o apresentados estudos verificando a influ&#234;ncia do treinamento aer&#243;bico sobre os &#237;ndices de vasodilata&#231;&#227;o endot&#233;lio-dependente, espessura m&#233;dia-&#237;ntima, e fatores de risco coronarianos.</p>
    <p>
      <bold>Exerc&#237;cio aer&#243;bico e vasodilata&#231;&#227;o endot&#233;lio-dependente</bold>
    </p>
    <p>A fun&#231;&#227;o endotelial irregular est&#225; amplamente relacionada a fatores de risco predisponentes a aterosclerose, como: hipercolesterolemia, obesidade, hipertens&#227;o, diabetes e tabagismo. O &#237;ndice de vasodilata&#231;&#227;o endot&#233;lio-dependente tem sido consistentemente utilizado em estudos como um indicador da fun&#231;&#227;o endotelial. Tal &#237;ndice parece ser capaz de identificar pacientes de alto risco. Ainda assim, maiores investiga&#231;&#245;es necessitam ser feitas para essa afirma&#231;&#227;o<sup>4</sup>. Contudo, a utiliza&#231;&#227;o da vasodilata&#231;&#227;o endot&#233;lio-dependente gera um par&#226;metro da condi&#231;&#227;o da integridade arterial, e, por esse motivo, muitos estudos t&#234;m utilizado tal avalia&#231;&#227;o.</p>
    <p>Segundo Da Luz e cols.<sup>12</sup>, o principal motivo da redu&#231;&#227;o da vasodilata&#231;&#227;o endot&#233;lio-dependente est&#225; na disfun&#231;&#227;o do endot&#233;lio em responder positivamente ao &#243;xido n&#237;trico. A ativa&#231;&#227;o da guanilato ciclase pelo &#243;xido n&#237;trico encontra-se dificultada em pessoas com disfun&#231;&#227;o endotelial. Por essa raz&#227;o, deixa de existir o ac&#250;mulo de monofosfato de guanosina c&#237;clica no endot&#233;lio, e, conseq&#252;entemente, a vasodilata&#231;&#227;o endot&#233;lio-dependente fica comprometida.</p>
    <p>A rela&#231;&#227;o do exerc&#237;cio aer&#243;bico com o &#237;ndice de vasodilata&#231;&#227;o endot&#233;lio-dependente tem sido estudada, ainda que recentemente n&#227;o se encontrem muitos estudos sobre o tema. Al&#233;m disso, os estudos t&#234;m utilizado diferentes tipos de exerc&#237;cios e diferentes tipos de popula&#231;&#227;o (normal, hipertensa, coronariana); sendo assim, cada situa&#231;&#227;o deve ser vista especificamente, n&#227;o podendo haver generaliza&#231;&#227;o dos resultados.</p>
    <p>Estudos verificaram que o exerc&#237;cio aer&#243;bico regular pode prevenir a perda da vasodilata&#231;&#227;o endot&#233;lio-dependente, al&#233;m de restaurar os n&#237;veis pr&#233;vios em homens de meia-idade e idosos sedent&#225;rios<sup>13</sup>. Quando comparados homens aerobicamente treinados e homens sedent&#225;rios, os primeiros apresentam uma vasodilata&#231;&#227;o endot&#233;lio-dependente preservada em rela&#231;&#227;o aos sedent&#225;rios<sup>14</sup>.</p>
    <p>Clarkson e cols.<sup>15</sup> encontraram resultados positivos de um programa de dez semanas de exerc&#237;cios aer&#243;bicos e anaer&#243;bicos em militares saud&#225;veis. O treinamento aumentou a vasodilata&#231;&#227;o endot&#233;lio-dependente nesses indiv&#237;duos. Gokce e cols.<sup>16</sup> tamb&#233;m encontraram um aumento significativo da vasodilata&#231;&#227;o endot&#233;lio-dependente da art&#233;ria tibial posterior com um programa de dez semanas de exerc&#237;cio aer&#243;bico moderado, e de predomin&#226;ncia de membros inferiores. No entanto, a vasodilata&#231;&#227;o de membros superiores n&#227;o aumentou significativamente, talvez em raz&#227;o da especificidade do exerc&#237;cio proposto.</p>
    <p>Ao analisar pessoas com hipertens&#227;o essencial submetidas a doze semanas de exerc&#237;cio aer&#243;bico (30 min, 5-7 X<bold>/</bold>semana) com intensidade de 52 &#177; 9% do VO<sub>2 M&#225;x.</sub>, Higashi e cols.<sup>17</sup> encontraram um aumento significativo da vasodilata&#231;&#227;o endot&#233;lio-dependente em resposta &#224; acetilcolina. Nesse mesmo estudo, indiv&#237;duos normotensos tamb&#233;m demonstraram um aumento da vasodilata&#231;&#227;o endot&#233;lio-dependente. A resposta ao dinitrato de isoss&#243;rbido, um vasodilatador endot&#233;lio-independente, n&#227;o se alterou ap&#243;s o treinamento em ambos os grupos.</p>
    <p>Indiv&#237;duos acometidos por infarto agudo do mioc&#225;rdio submetidos a tr&#234;s meses de treinamento aer&#243;bico (cicloerg&#244;metro), com intensidade de 75% da freq&#252;&#234;ncia card&#237;aca pico de exerc&#237;cio, tamb&#233;m demonstraram aumento da vasodilata&#231;&#227;o endot&#233;lio-dependente. Contudo, ap&#243;s um m&#234;s de destreinamento, os benef&#237;cios desapareceram<sup>18</sup>. Tal resultado sugere que mesmo indiv&#237;duos com hist&#243;rico de algum evento card&#237;aco podem apresentar melhorias da fun&#231;&#227;o endotelial.</p>
    <p>Analisando o efeito de diferentes intensidades de exerc&#237;cio aer&#243;bico sobre a art&#233;ria, Goto e cols.<sup>11</sup> verificaram que a intensidade moderada (50% VO<sub>2 M&#225;x</sub>) foi a &#250;nica capaz de melhorar a vasodilata&#231;&#227;o endot&#233;lio-dependente. O exerc&#237;cio de intensidade leve (25% VO<sub>2 M&#225;x</sub>) e o de alta intensidade (75% VO<sub>2 M&#225;x</sub>) n&#227;o proporcionaram nenhum benef&#237;cio &#224; fun&#231;&#227;o endotelial. Com respeito &#224; alta intensidade, essa foi respons&#225;vel por um aumento do estresse oxidativo, aspecto danoso &#224; parede arterial. Por essa raz&#227;o, a intensidade moderada parece ser a mais apropriada para indiv&#237;duos sedent&#225;rios que buscam benef&#237;cios cardiovasculares por meio do exerc&#237;cio aer&#243;bico regular.</p>
    <p>Apesar dos estudos referenciarem o exerc&#237;cio aer&#243;bico regular como o respons&#225;vel pela modifica&#231;&#227;o do &#237;ndice de vasodilata&#231;&#227;o endot&#233;lio-dependente, uma quest&#227;o fundamental aparece nesse contexto. O quanto a aptid&#227;o aer&#243;bica responde por essas modifica&#231;&#245;es?</p>
    <p>A aptid&#227;o cardiorrespirat&#243;ria demonstrou estar relacionada &#224; menor progress&#227;o ateroscler&#243;tica em homens<sup>19</sup>. Contudo, sua associa&#231;&#227;o com a vasodilata&#231;&#227;o endot&#233;lio-dependente tem sido pouco estudada.</p>
    <p>Uma maior capacidade aer&#243;bica (VO<sub>2 M&#225;x</sub>)<sup>20</sup> esteve relacionada a um maior di&#226;metro arterial (r = 0,66, p &lt; 0,002) durante estado de hiperemia provocada, em homens idosos treinados (68,5 &#177; 2,3 anos) comparados a idosos sedent&#225;rios (64,7 &#177; 1,4 ano). Tal fator se deve &#224; maior capacidade de vasodilata&#231;&#227;o endot&#233;lio-dependente nos indiv&#237;duos treinados, os quais se exercitavam no m&#237;nimo tr&#234;s vezes por semana, por pelo menos uma hora ao dia.</p>
    <p>Esse resultado levanta a possibilidade de estar se relacionando preferencialmente a capacidade aer&#243;bica com a fun&#231;&#227;o endotelial, pois &#233; uma medida muito mais precisa. Ao contr&#225;rio disso, os programas de treinamento s&#227;o pass&#237;veis da falta de assiduidade, falta de ades&#227;o, e da pr&#243;pria resposta fisiol&#243;gica individual ao treino, pois as mesmas vari&#225;veis n&#227;o podem ser completamente controladas nos programas de exerc&#237;cio.</p>
    <p>Apesar de estudos com crian&#231;as e adolescentes n&#227;o serem comuns, Watts e cols<sup>21</sup> encontraram resultado positivo na normaliza&#231;&#227;o da fun&#231;&#227;o circulat&#243;ria em adolescentes obesos utilizando um programa de treinamento em circuito, que consistiu de cicloerg&#244;metro e treinamento resistido. Al&#233;m disso, houve um aumento da capacidade funcional, for&#231;a muscular e melhoria na composi&#231;&#227;o corporal desses adolescentes. Estudos reportaram que a preven&#231;&#227;o de doen&#231;as cardiovasculares deve ter in&#237;cio desde a inf&#226;ncia, pois os fatores de risco j&#225; est&#227;o presentes nessa fase<sup>22</sup>.</p>
    <p>Parece que mesmo havendo diferen&#231;as nos exerc&#237;cios e intensidade utilizados, os estudos t&#234;m demonstrado que o exerc&#237;cio aer&#243;bico &#233; capaz de melhorar e restaurar a vasodilata&#231;&#227;o endot&#233;lio-dependente.</p>
    <p>
      <bold>Exerc&#237;cio aer&#243;bico e espessura m&#233;dia-&#237;ntima</bold>
    </p>
    <p>O espessamento m&#233;dia-&#237;ntima da art&#233;ria constitui-se num dos est&#225;gios da aterosclerose e, conseq&#252;entemente, sua avalia&#231;&#227;o pode ajudar no diagn&#243;stico e progn&#243;stico do processo aterog&#234;nico<sup>5</sup>. Rosfors e cols.<sup>23</sup> averiguaram que a espessura m&#233;dia-&#237;ntima esteve relacionada ao grau de aterosclerose nas bifurca&#231;&#245;es das car&#243;tidas. Zureik e cols.<sup>6</sup> tamb&#233;m constataram que a espessura m&#233;dia-&#237;ntima elevada predisse a ocorr&#234;ncia de placas ateroscler&#243;ticas em pessoas idosas.</p>
    <p>Ainda que de forma pouco expressiva, estudos t&#234;m sido conduzidos relacionando a espessura m&#233;dia-&#237;ntima com programas e estado de treinamento.</p>
    <p>Rauramaa e cols.<sup>24</sup> n&#227;o verificaram a diminui&#231;&#227;o da espessura m&#233;dia-&#237;ntima em homens de meia-idade (tratados e n&#227;o-tratados com estatinas) submetidos a um programa de seis anos de exerc&#237;cio aer&#243;bico moderado, e analisados por meio de ultra-sonografia (10 MHZ) da bifurca&#231;&#227;o da car&#243;tida. No entanto, quando um subgrupo de indiv&#237;duos que n&#227;o utilizavam estatinas foi analisado separadamente, o exerc&#237;cio mostrou-se eficiente na diminui&#231;&#227;o do progresso ateroscler&#243;tico. Dessa forma, os autores conclu&#237;ram que o medicamento pode ter mascarado os efeitos do exerc&#237;cio nessa popula&#231;&#227;o. Por&#233;m, discord&#226;ncias acerca do estudo de Rauramaa e cols. t&#234;m sido descritas em recentes cr&#237;ticas publicadas por autores da &#225;rea<sup>25,26</sup>.</p>
    <p>Dinenno e cols.<sup>27</sup> realizaram um estudo com dois momentos distintos, consistindo de uma an&#225;lise transversal e uma interven&#231;&#227;o com treinamento aer&#243;bico. Os autores verificaram a influ&#234;ncia do treinamento aer&#243;bico na remodela&#231;&#227;o arterial. No primeiro momento, os autores analisaram 55 homens aerobicamente treinados (47 &#177; 2 anos) e 53 sedent&#225;rios (47 &#177; 2 anos). Foi verificado que os indiv&#237;duos treinados apresentavam um di&#226;metro luminal da art&#233;ria femoral comum 7% maior que os sedent&#225;rios, al&#233;m disso a espessura m&#233;dia-&#237;ntima e a raz&#227;o m&#233;dia-&#237;ntima/l&#250;men dos treinados era 16% e 21% menor, respectivamente. Para a realiza&#231;&#227;o do estudo intervencional, os autores selecionaram 22 indiv&#237;duos (51 &#177; 2 anos) do grupo de sedent&#225;rios, submetendo-os a tr&#234;s meses de treinamento aer&#243;bico. Em m&#233;dia, os indiv&#237;duos se exercitaram 13,5 &#177; 1,0 semanas, 5,3 &#177; 0,3 dias, 45 &#177; 2 min. por sess&#227;o, a 73 &#177; 1% da FC m&#225;xima. Ap&#243;s o per&#237;odo de treino, verificou-se um aumento de 9% no di&#226;metro do l&#250;men da art&#233;ria femoral comum, bem como uma diminui&#231;&#227;o de 14% e 20% na espessura m&#233;dia-&#237;ntima e na raz&#227;o m&#233;dia-&#237;ntima/l&#250;men, respectivamente.</p>
    <p>O mesmo grupo de autores<sup>28</sup>, contudo, n&#227;o encontrou resultado positivo do exerc&#237;cio aer&#243;bio na diminui&#231;&#227;o do enrijecimento arterial, em um estudo posterior. O programa de treinamento de tr&#234;s meses n&#227;o foi significativamente eficiente na promo&#231;&#227;o de benef&#237;cios arteriais. Nesse estudo, encontrou-se uma rela&#231;&#227;o positiva entre idade e &#237;ndice de espessura m&#233;dia-&#237;ntima arterial. Dessa forma, o exerc&#237;cio n&#227;o conseguiu evitar as conseq&#252;&#234;ncias do avan&#231;o de idade.</p>
    <p>Dinenno e cols.<sup>29</sup> reportaram que o espessamento da parede arterial relacionado ao aumento da idade est&#225; intimamente ligado &#224; eleva&#231;&#227;o da atividade simp&#225;tica.</p>
    <p>Ao analisar mulheres p&#243;s-menopausa, Moreau e cols.<sup>30</sup> verificaram que tanto a terapia de reposi&#231;&#227;o hormonal como o exerc&#237;cio aer&#243;bico regular estiveram associados com um menor &#237;ndice de espessura m&#233;dia-&#237;ntima da art&#233;ria. Al&#233;m da classifica&#231;&#227;o de sedent&#225;rio ou treinado, a capacidade aer&#243;bica m&#225;xima foi utilizada para divis&#227;o dos grupos. Em conjunto, a reposi&#231;&#227;o hormonal e o exerc&#237;cio aer&#243;bico regular promoveram mudan&#231;as maiores na espessura m&#233;dia-&#237;ntima do que na situa&#231;&#227;o isolada. Contudo, tanto o grupo exerc&#237;cio aer&#243;bico regular quanto o grupo reposi&#231;&#227;o hormonal j&#225; foram capazes de mudan&#231;as significativas na espessura m&#233;dia-&#237;ntima da art&#233;ria comparado ao grupo sedent&#225;rio que n&#227;o utilizava reposi&#231;&#227;o hormonal.</p>
    <p>Em virtude de algumas controv&#233;rsias sobre os efeitos do exerc&#237;cio aer&#243;bico na espessura m&#233;dia-&#237;ntima &#233; necess&#225;rio maior n&#250;mero de investiga&#231;&#245;es sobre o assunto para verificar se realmente o exerc&#237;cio &#233; eficiente na restaura&#231;&#227;o da integridade arterial nesse est&#225;gio da aterosclerose.</p>
    <p>
      <bold>Efeitos do exerc&#237;cio aer&#243;bico sobre os fatores de risco ateroscler&#243;ticos</bold>
    </p>
    <p>Apesar de os &#237;ndices de vasodilata&#231;&#227;o endot&#233;lio-dependente e de espessura arterial serem &#243;timos indicativos da integridade arterial, v&#225;rios fatores de risco atuam no desenvolvimento de doen&#231;as cardiovasculares. A diminui&#231;&#227;o dos fatores de risco deve ser realizada na preven&#231;&#227;o e no controle da aterosclerose<sup>31</sup>.</p>
    <p>O treinamento aer&#243;bico &#233; uma &#243;tima ferramenta para modifica&#231;&#227;o dos fatores de risco (<xref ref-type="fig" rid="figura2">fig. 2</xref>). Como exposto por Rique e cols.<sup>32</sup>, a modifica&#231;&#227;o dos h&#225;bitos de vida, entre eles a nutri&#231;&#227;o e a pr&#225;tica de exerc&#237;cio f&#237;sico regular, pode levar &#224; diminui&#231;&#227;o dos riscos de doen&#231;as cardiovasculares. O exerc&#237;cio pode atuar para amenizar dislipidemias, diabetes, obesidade e hipertens&#227;o.</p>
    <fig id="figura2">
      <graphic xlink:href="1678-4170-abc-87-05-e226-00036-gf02.jpg"/></fig>
    <p>A dislipidemia caracteriza-se principalmente pelos altos &#237;ndices de LDL-C e triglicer&#237;deos, e baixos &#237;ndices de HDL-C<sup>1,2,12,33</sup>. O exerc&#237;cio &#233; uma ferramenta para modifica&#231;&#227;o do perfil lip&#237;dico, atuando de forma significativa no aumento dos &#237;ndices de HDL-C e redu&#231;&#227;o do LDL-C e dos triglicer&#237;deos s&#233;ricos. Em uma metan&#225;lise, Kelley &amp; Kelley<sup>34</sup> demonstraram que o exerc&#237;cio aer&#243;bico (<underline>&gt;</underline> 8 semanas) &#233; capaz de aumentar significativamente os n&#237;veis de HDL<sub>2</sub>-C em adultos (<underline>&gt;</underline> 18 anos).</p>
    <p>Roberts e cols.<sup>35</sup> constataram que o exerc&#237;cio aer&#243;bio por um per&#237;odo de tr&#234;s semanas melhorou a press&#227;o arterial, o estresse oxidativo, disponibilidade de &#243;xido n&#237;trico, e o perfil metab&#243;lico. Lalonde e cols.<sup>36</sup> observaram que as interven&#231;&#245;es mais intensas (dieta rigorosa com exerc&#237;cio) propiciaram melhores resultados com rela&#231;&#227;o aos efeitos no perfil l&#237;pidico e qualidade de vida do que interven&#231;&#245;es menos intensas (dieta, dieta rigorosa sem exerc&#237;cio). A dieta associada com o exerc&#237;cio propiciou maior redu&#231;&#227;o de LDL-C, e aumento do HDL-C.</p>
    <p>Couillard e cols<sup>37</sup> verificaram que vinte semanas de treinamento aer&#243;bico de <italic>endurance</italic> foi mais efetivo no aumento do HDL-C para pessoas com altos &#237;ndices de triglicer&#237;deos e baixos n&#237;veis de HDL-C, do que para pessoas com &#237;ndices normais de trigliceridemia e baixos n&#237;veis de HDL-C.</p>
    <p>Analisando um grupo de &#237;ndios asi&#225;ticos, Bhalodkar e cols.<sup>38</sup> verificaram que o grupo que se exercitava habitualmente apresentou melhor &#237;ndice de HDL-C de subfra&#231;&#227;o maior. Al&#233;m disso, o tamanho das part&#237;culas de HDL-C era especialmente maior no grupo ativo comparado ao grupo inativo.</p>
    <p>Estudando uma comunidade rural, Matos &amp; Ladeia<sup>39</sup> verificaram que os n&#237;veis normais de triglicer&#237;deos s&#233;ricos e a rela&#231;&#227;o cintura-quadril (RCQ) normal estiveram relacionados ao maior gasto cal&#243;rico e ao melhor perfil de risco.</p>
    <p>Outro problema de propor&#231;&#227;o mundial &#233; a obesidade, que se constitui em um fator de risco secund&#225;rio, no entanto extremamente ligado ao processo ateroscler&#243;tico. Ainda assim, a obesidade central (abdominal) &#233; um melhor preditor para doen&#231;as do cora&#231;&#227;o do que a obesidade geral. Pitanga &amp; Lessa<sup>40</sup> demonstraram que os &#237;ndices circunfer&#234;ncia de cintura (C) e raz&#227;o circunfer&#234;ncia cintura quadril (RCCQ) s&#227;o mais apropriados do que o IMC para discrimina&#231;&#227;o dos riscos coronarianos elevados.</p>
    <p>Lakka e cols.<sup>41</sup> encontraram uma rela&#231;&#227;o entre obesidade abdominal (alta circunfer&#234;ncia de cintura, e alta rela&#231;&#227;o cintura quadril) e desenvolvimento da aterosclerose, independentemente da obesidade geral e de outros fatores de risco. O principal fator para essa rela&#231;&#227;o &#233; que a obesidade abdominal est&#225; diretamente ligada &#224; gordura visceral, a qual, por sua vez, &#233; um indicador de efeitos metab&#243;licos desfavor&#225;veis. Tais efeitos acarretam resist&#234;ncia a insulina, intoler&#226;ncia a glicose, hipertrigliceridemia, eleva&#231;&#227;o dos &#237;ndices de LDL-C, diminui&#231;&#227;o dos &#237;ndices de HDL-C, entre outros.</p>
    <p>Em um estudo realizado com ratos wistars, Kretschmer e cols.<sup>42</sup> demonstraram que um programa de cinco semanas de exerc&#237;cio aer&#243;bico foi eficiente na manuten&#231;&#227;o e redu&#231;&#227;o de peso corporal dos ratos. Pelo car&#225;ter de an&#225;lise desse estudo (<italic>post-mortem</italic>), os resultados refletem grande fidedignidade, visto que a quantifica&#231;&#227;o de gordura torna-se muito mais precisa.</p>
    <p>Savage e cols.<sup>43</sup> verificaram que um programa de quatro meses de treinamento, consistindo em longas caminhadas (60-90 min.), cinco a sete vezes por semana<sup>1</sup>, a uma intensidade de 50%-60% do VO<sub>2 pico</sub>, foi eficiente na redu&#231;&#227;o de peso corporal (-4,6 kg) em pacientes sobrepesos coronarianos. Al&#233;m do peso corporal, houve redu&#231;&#227;o do porcentual de gordura (-2,9%), do tecido adiposo subcut&#226;neo (-12%) e do tecido adiposo visceral (-14%). Concomitantemente, mudan&#231;as no perfil lip&#237;dico tamb&#233;m puderam ser notadas, sendo a principal uma redu&#231;&#227;o de 23,7% nos n&#237;veis de triglicer&#237;deos.</p>
    <p>Outro fator de risco para o desenvolvimento ateroscler&#243;tico &#233; o diabetes, mesmo para pessoas assintom&#225;ticas<sup>44,45</sup>. O principal motivo para isso &#233; o metabolismo irregular da glicose em diab&#233;ticos e, em conseq&#252;&#234;ncia, o metabolismo acelerado das gorduras nessa popula&#231;&#227;o<sup>46</sup>.</p>
    <p>Nishida e cols.<sup>47</sup> verificaram que doze semanas de treinamento (sessenta minutos di&#225;rios, cinco vezes por semana) na intensidade de limiar de lactato melhorou a sensitividade insul&#237;nica. Tal sensitividade foi refletida principalmente pela melhor sensitividade insul&#237;nica perif&#233;rica e efetividade perif&#233;rica da glicose. Contudo, verificou-se que os efeitos do treinamento s&#227;o perdidos ap&#243;s uma semana de destreinamento.</p>
    <p>Short e cols.<sup>48</sup> constataram que quatro meses de treinamento aer&#243;bico promoveram melhorias na sensitividade insul&#237;nica somente em pessoas mais jovens, mas n&#227;o em pessoas de meia-idade e idosas. Ainda assim, houve benef&#237;cios em todas as faixas et&#225;rias para o conte&#250;do mitocondrial e capacidade aer&#243;bica.</p>
    <p>A hipertens&#227;o arterial parece ser um dos principais fatores de risco para o desenvolvimento ateroscler&#243;tico, pois est&#225; intimamente ligada ao desencadeamento de inflama&#231;&#245;es da parede arterial<sup>49</sup>. Tais inflama&#231;&#245;es comprometem a vasodilata&#231;&#227;o normal da art&#233;ria, promovendo um aumento sistem&#225;tico da press&#227;o arterial sist&#243;lica e diast&#243;lica, desencadeando um c&#237;rculo vicioso<sup>12</sup>.</p>
    <p>Estudos relacionando a redu&#231;&#227;o da press&#227;o arterial &#224; pr&#225;tica do exerc&#237;cio aer&#243;bico t&#234;m sido amplamente realizados. As respostas mais est&#225;veis da press&#227;o arterial ao exerc&#237;cio podem ser observadas ap&#243;s uma a dez semanas de treinamento<sup>50</sup>.</p>
    <p>O Col&#233;gio Americano de Medicina do Esporte (ACSM)<sup>51</sup> estabeleceu padr&#245;es para a intensidade do exerc&#237;cio objetivando redu&#231;&#227;o da press&#227;o arterial, estabelecendo que o hipertenso deve praticar exerc&#237;cio moderado, o qual deve ser de 40 a 60% do VO<sub>2</sub><sub>M&#225;x</sub>. Portanto, uma redu&#231;&#227;o de 10% com rela&#231;&#227;o &#224; posi&#231;&#227;o tomada em 1993. Quanto ao tempo de exerc&#237;cio, recomendam-se cerca de trinta minutos ou mais de exerc&#237;cio moderado diariamente, podendo acontecer de forma acumulativa ou intermitente. O ACSM esclarece que a redu&#231;&#227;o da press&#227;o arterial acontece por diversos fatores, entre eles: redu&#231;&#227;o da atividade nervosa simp&#225;tica, redu&#231;&#227;o da a&#231;&#227;o do sistema renina/angiotensina, melhor responsividade vascular, aumento da capilariza&#231;&#227;o, aumento do l&#250;men arterial, entre outros.</p>
    <p>Moreira e cols.<sup>52</sup> verificaram que o treinamento aer&#243;bico em duas intensidades diferentes (20% e 60% da carga m&#225;xima) no cicloerg&#244;metro, por um per&#237;odo de dez semanas, propiciaram resultados semelhantes na redu&#231;&#227;o da press&#227;o arterial ambulatorial.</p>
    <p>Takata e cols.<sup>53</sup> encontraram rela&#231;&#227;o positiva entre a atividade f&#237;sica e a redu&#231;&#227;o da hipertens&#227;o. O estudo foi realizado com 207 indiv&#237;duos, havendo alguns sem tratamento e outros com hipertens&#227;o de est&#225;gio 1 e 2. Os pesquisadores dividiram os sujeitos em grupos, conforme o n&#237;vel de atividade semanal: sedent&#225;rio controle, 30-60 min/semana, 61-90 min/semana, 91-120 min/semana, &gt;120 min/semana. O programa durou oito semanas, e a an&#225;lise foi feita ao final do mesmo. O resultado apontou que aqueles que se exercitaram tiveram redu&#231;&#245;es das press&#245;es sist&#243;lica e diast&#243;lica, e que o grupo controle n&#227;o apresentou altera&#231;&#227;o das press&#245;es. O grupo que realizou de 61-90 min/semana obteve melhores resultados do que o grupo que realizou 30-60 min/semana. N&#227;o houve redu&#231;&#245;es extras para os grupos que tiveram maiores volumes de exerc&#237;cio.</p>
    <p>O exerc&#237;cio aer&#243;bico, portanto, atua de maneira significativa na redu&#231;&#227;o dos fatores de risco cardiovasculares, como p&#244;de ser notado nos estudos descritos. Sendo assim, o exerc&#237;cio aer&#243;bico pode ser utilizado em popula&#231;&#245;es de risco com o prop&#243;sito de diminuir a preval&#234;ncia de doen&#231;as cardiovasculares.</p>
    <p>
      <bold>Marcadores inflamat&#243;rios em resposta ao exerc&#237;cio aer&#243;bico</bold>
    </p>
    <p>O aumento tecnol&#243;gico tem levado &#224; averigua&#231;&#227;o de marcadores inflamat&#243;rios ou pr&#243;-aterog&#234;nicos do exerc&#237;cio cr&#244;nico e agudo. Ers&#246;z e cols.<sup>54</sup> encontraram um aumento da agrega&#231;&#227;o plaquet&#225;ria induzida pelo col&#225;geno no exerc&#237;cio subm&#225;ximo. Quando realizado o exerc&#237;cio incremental m&#225;ximo, verificou-se tamb&#233;m o mesmo aumento da agrega&#231;&#227;o plaquet&#225;ria induzida pelo col&#225;geno e pelo ADP, al&#233;m de aumento dos n&#237;veis de tromboxina B<sub>2.</sub> Em um estudo de Duncan e cols.<sup>55</sup>, os indiv&#237;duos que treinaram mais intensamente e com maior freq&#252;&#234;ncia apresentaram maiores n&#237;veis de homociste&#237;na s&#233;rica, apesar de reduzirem a a&#231;&#227;o da insulina em jejum.</p>
    <p>Killewich e cols.<sup>56</sup> encontraram resultados positivos de um treinamento aer&#243;bico de seis meses sobre os &#237;ndices fibrinol&#237;ticos em sujeitos com claudica&#231;&#227;o intermitente. O exerc&#237;cio demonstrou ser eficiente na redu&#231;&#227;o do inibidor da ativa&#231;&#227;o plasminog&#234;nica &#150; 1 (PAI-1), e no aumento do ativador do plasminog&#234;nio (tPA), portanto um aumento na atividade fibrinol&#237;tica. O treino aer&#243;bico demonstrou ser, nesse estudo, eficiente no tratamento da doen&#231;a arterial perif&#233;rica.</p>
    <p>
      <bold>Recomenda&#231;&#245;es</bold>
    </p>
    <p>Atualmente, &#233; evidente a diferencia&#231;&#227;o que existe entre atividade f&#237;sica e exerc&#237;cio f&#237;sico. A primeira consiste em qualquer movimenta&#231;&#227;o corporal que resulte em disp&#234;ndio energ&#233;tico acima dos n&#237;veis de repouso. O exerc&#237;cio, por sua vez, &#233; um conjunto planificado, estruturado e repetitivo de atividades f&#237;sicas, possuindo o prop&#243;sito de melhorar ou manter a aptid&#227;o f&#237;sica. Apesar das diferen&#231;as, parece ser consciente sugerir a pr&#225;tica da atividade f&#237;sica como forma de modificar os h&#225;bitos sedent&#225;rios da popula&#231;&#227;o, e como uma prepara&#231;&#227;o para o ingresso em um programa de exerc&#237;cios f&#237;sicos.</p>
    <p>O American Heart Association (AHA)<sup>57</sup> possui uma recomenda&#231;&#227;o para a pr&#225;tica de atividades f&#237;sicas na preven&#231;&#227;o da aterosclerose (<xref ref-type="fig" rid="quadro1">quadro 1</xref>). Tal recomenda&#231;&#227;o &#233; embasada no posicionamento sobre a atividade f&#237;sica do ACSM<sup>58</sup>, o qual tem sido adotado pela maioria dos programas pertinentes a tal assunto no mundo. Com a ado&#231;&#227;o de tal recomenda&#231;&#227;o &#233; poss&#237;vel diminuir a freq&#252;&#234;ncia de doen&#231;as card&#237;acas, os fatores de risco, e modificar o perfil lip&#237;dico.</p>
    <fig id="quadro1">
      <graphic xlink:href="1678-4170-abc-87-05-e226-00036-gf03.jpg"/></fig>
    <p>Para maior ades&#227;o das recomenda&#231;&#245;es, ambos os &#243;rg&#227;os sugerem que sejam feitas atividades do dia-a-dia, como: jardinagem, subir escadas, caminhar, andar de bicicleta etc. A dura&#231;&#227;o m&#237;nima de cada fra&#231;&#227;o de atividade deve ser de dez minutos. Sendo assim, podem ser feitas tr&#234;s fra&#231;&#245;es de dez minutos durante o dia. Contudo, Peterson e cols.<sup>59</sup> encontraram resultados id&#234;nticos quanto ao gasto cal&#243;rico em trinta minutos cont&#237;nuos e tr&#234;s fra&#231;&#245;es de dez minutos. Ainda assim, pesquisas s&#227;o necess&#225;rias para verificar diferen&#231;as quanto &#224;s modifica&#231;&#245;es dos fatores de risco nesses dois tipos de situa&#231;&#227;o.</p>
    <p>
      <bold>Conclus&#227;o</bold>
    </p>
    <p>Percebe-se, portanto, que o exerc&#237;cio aer&#243;bico tem demonstrado ser eficiente na preven&#231;&#227;o da aterosclerose, conseguindo restaurar a fun&#231;&#227;o endotelial normal e atenuar os fatores de risco em diversos estudos citados. A intensidade moderada parece ser a mais adequada para a preven&#231;&#227;o da aterosclerose. Outrossim, a atividade f&#237;sica parece ser uma &#243;tima estrat&#233;gia para iniciar a modifica&#231;&#227;o dos h&#225;bitos sedent&#225;rios, al&#233;m de preparar o indiv&#237;duo para ingressar em um programa de exerc&#237;cio f&#237;sico.</p>
    <p>Apesar de a maioria dos estudos apontar benef&#237;cios do exerc&#237;cio aer&#243;bico sobre a aterosclerose, &#233; necess&#225;ria maior investiga&#231;&#227;o acerca do assunto, a fim de esclarecer melhor os mecanismos fisiol&#243;gicos subjacentes.</p>
    <p>
      <bold>Refer&#234;ncias</bold>
    </p>
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    <p>47. Nishida Y, Tokuyama K, Nagasaka S, et al. Effect of moderate exercise training on peripheral glucose effectiveness, insulin sensitivity, and endogenous glucose production in healthy humans estimated by two-compartment-labeled minimal model. Diabetes. 2004; 53: 315-20.</p>
    <p>48. Short KR, Vittone JL, Bigelow ML, et al. Impact of aerobic exercise training on age-related changes in insulin sensitivity and muscle oxidative capacity. Diabetes. 2003; 52: 1888-96.</p>
    <p>49. Li JJ, Chen JL. Inflammation may be a bridge connecting hypertension and atherosclerosis. Medical Hypothesis. 2004: 1-5.</p>
    <p>50. Hagberg JM, Park JJ, Brown MD. The Role of exercise training in the treatment of hypertension. Sports Med. 2000; 30(3):193-206.</p>
    <p>51. ACSM. Position stand: Exercise and hypertension. Med Sci Sports Exerc. 2004; 533-53.</p>
    <p>52. Moreira WD, Fuchs FD, Ribeiro JP, Appel LJ. The effects of two aerobic training intensities on ambulatory blood pressure in hypertensive patients: a randomized trial. J Clin Epidemiol. 1999; 52(7): 637-42.</p>
    <p>53. Takata KI, Ohta T, Tanaka H. How much exercise is required to reduce blood pressure in essential hypertensives: a dose-response study. Am J Hypertension. 2003; 16: 629-33.</p>
    <p>54. Ers&#246;z G, Zergeroglu AM, Fi&#231;icilar H, &#214;zcan H, &#214;ztekin P, Ayta&#231; S, et al. Effect of submaximal and incremental upper extremity exercise on platelet function and the role of blood shear stress. Thromb Res. 2003; 08: 297-300.</p>
    <p>55. Duncan GE, Perri MG, Anton SD, Limacher MC, Martin AD, Lowenthal DT, et al. Effects of exercise on emerging and traditional cardiovascular risk factors. Prev Med. 2004; [s.v]: 1-9.</p>
    <p>56. Killewich LA, Macko RF, Montgomery PS, Willey LA, Gardner AW. Exercise training enhances endogenous fibrinolysis in peripheral arterial disease. J Vasc Surgery. 2004;40(4): 741-5.</p>
    <p>57. AHA. Exercise and physical activity in the prevention and treatment of atherosclerotic cardiovascular disease. Circulation. 2003; 107: 3109-16.</p>
    <p>58. ACSM. ACSM'S Guidelines for Exercise Testing and Prescription. 7th Ed. Baltimore (MA): Lippincott Willians and Wilkins, 2006.</p>
    <p>59. Peterson MJ, Palmer DR, Laubach LL. Comparison of caloric expenditure in intermittent and continuous walking bouts. J Strength Conditioning Res. 2004; 18(2): 373-7.</p>
    <p>
      <fn id="back" fn-type="corresp">
        <p>
          <graphic xlink:href="1678-4170-abc-87-05-e226-00036-e01.jpg"/></p>
        <p>
          <bold>Correspond&#234;ncia:</bold>
        </p>
        <p> Jeffer Eidi Sasaki </p>
        <p> Rua Baltazar Carrasco dos Reis, 908 </p>
        <p> 80215-160 &#150; Curitiba, PR </p>
        <p> E-mail: </p>
        <p>
          <email xlink:href="jeffersasaki@gmail.com">jeffersasaki@gmail.com</email>
        </p>
      </fn>
    </p>
    <p>Recebido em 25/10/05; revisado recebido em 20/03/06; aceito em 30/03/06.</p>
  </body>
  <sub-article article-type="translation" id="TRen" xml:lang="en">
    <front-stub>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Clinical Update</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title xml:lang="en">The role of aerobic exercise on endothelial function and on cardiovascular risk factors</article-title>
      </title-group>
    </front-stub>
    <body>
      <p>
        <bold>CLINICAL UPDATE</bold>
      </p>
      <p>
        <bold>The role of aerobic exercise on endothelial function and on cardiovascular risk factors</bold>
      </p>
      <p>
        <bold>Jeffer Eidi Sasaki; Maria Gisele dos Santos</bold>
      </p>
      <p>Universidade Federal do Paran&#225;, Curitiba, PR, Brazil</p>
      <p>
        <xref ref-type="corresp" rid="back-body2">Mailing Address</xref>
      </p>
      <p><bold>Key words:</bold> Atherosclerosis, aerobic exercise, risk factors.</p>
      <p>Coronary artery diseases, including atherosclerosis, have become the major cause of death in the modern civilization<sup>1,2</sup>. This problem results from many aspects of the modern lifestyle: irregular nutrition, smoking, excess alcoholic beverage consumption, daily stress and, above all, a sedentary lifestyle.</p>
      <p>These habits lead to the development of risk factors related to atherosclerosis. The formation of atherosclerotic plaques or atheromas is directly related to coronary events such as infarction, ischemic heart disease, and apoplexy<sup>3</sup>.</p>
      <p>Primary stages of atherosclerosis may be detected through observation of some changes in the arterial wall. One of them is the decrease in endothelium-dependent vasodilation, which is related to a high risk of development of atherosclerosis<sup>4</sup>. Another change is the intima-media thickening, which is a primary stage of atherosclerosis<sup>5,6</sup> and may be used to monitor asymptomatic individuals.</p>
      <p>Prevention, when such changes are diagnosed, may stop the progression of atherosclerosis, thus reestablishing the arterial integrity (<xref ref-type="fig" rid="figura1-body2">Figure 1</xref>).</p>
      <fig id="figura1-body2">
        <graphic xlink:href="1678-4170-abc-87-05-e226-00036-gf01-en.jpg"/></fig>
      <p>The relation between physical exercises and endothelium-dependent vasodilation and intima-media thickness has been studied. However, there are few studies on this issue. Yet, the results have suggested that aerobic exercise is efficient to improve these indexes. The objective of this study is to contribute to the current discussion through a review of the literature.</p>
      <p>
        <bold>Aerobic exercise and atherosclerosis</bold>
      </p>
      <p>Etymologically, the word atherosclerosis comes from the Greek "athero" (paste, gruel) and "sclerosis" (hardening)<sup>2</sup>. Atherosclerosis is a chronic degenerative disease characterized by a narrowing of the arterial lumen due to deposition of fat and formation of fibrolipid plaques<sup>2,3,7</sup>.</p>
      <p>Aerobic exercise is defined as that where predominant oxygen demand occurs. It enables the oxidative burning of energetic substances, including carbohydrates, fats and proteins. The proportion of utilization of these substrates depends on the exercise intensity<sup>8</sup>.</p>
      <p>Cardiovascular alterations are widely reported in the literature. The main of these alterations are: increase in heart volume, increase in ejection volume, increase in blood erythrocyte concentration and hemoglobin, reduction in resting heart rate and blood pressure, improvement of peripheral vascularization, and others<sup>8-10</sup>.</p>
      <p>However, in addition to these benefits, atherosclerotic patients may present improved arterial reactivity and intima-media thickness with aerobic training. Studies<sup>11</sup> have demonstrated that moderate intensity, together with regularity of training, seems to be efficient in promoting benefits to the endothelial function. In the following topics, studies on the influence of aerobic training on endothelium-dependent vasodilation, intima-media thickness, and coronary risk factors are presented.</p>
      <p>
        <bold>Aerobic exercise and endothelium-dependent vasodilation</bold>
      </p>
      <p>Irregular endothelial function is largely related to risk factors predisposing to atherosclerosis, such as hypercholesterolemia, obesity, hypertension, diabetes and smoking. The endothelium-dependent vasodilation index has been consistently used in studies as an indicator of the endothelial function. This index seems to be capable of identifying high risk patients. Yet, further investigation is necessary to confirm this possibility<sup>4</sup>. However, the use of endothelium-dependent vasodilation generates a parameter of the arterial integrity condition and, for this reason, many studies have used this assessment.</p>
      <p>According to Da Luz et al<sup>12</sup>, the major reason for the reduction of the endothelium-dependent vasodilation lies in the dysfunction of the endothelium to respond positively to nitric oxide. Guanylate cyclase activation by nitric oxide is impaired in individuals with endothelial dysfunction. For this reason, accumulation of cyclic guanosine monophosphate in the endothelium fails to occur, and, consequently, the endothelium-dependent vasodilation is affected.</p>
      <p>The relationship between aerobic exercise and endothelium-dependent vasodilation index has been studied, although few recent studies on this subject are found . Additionally, studies have used different types of exercises and different types of populations (normal, hypertensive, coronary patients). Thus, each situation must be considered individually, and the results should not be generalized.</p>
      <p>Studies have verified that regular aerobic exercise may prevent the loss of endothelium-dependent vasodilation, in addition to restoring previous levels in sedentary middle-aged and elderly men<sup>13</sup>. When compared to sedentary men, aerobically trained men show a preserved endothelium-dependent vasodilation<sup>14</sup>.</p>
      <p>Clarkson et al<sup>15</sup> found positive results of a 10-week aerobic and anaerobic exercise training program in healthy military recruits. Training increased endothelium-dependent vasodilation in these individuals. Gokce et al<sup>16</sup> also found a significant increase in endothelium-dependent vasodilation of the posterior tibial artery with a 10-week moderate intensity aerobic exercise program with emphasis in the legs. However, vasodilation in the arms did not increase significantly, perhaps due to the specificity of the exercise proposed.</p>
      <p>Higashi et al<sup>17</sup> analyzed individuals with essential hypertension undergoing a 12-week aerobic exercise program (30 minutes, 5-7 X/week) with an intensity of 52 &#177; 9% of the VO<sub>2 Max</sub> and found a significant increase of the endothelium-dependent vasodilation in response to acetylcholine. In that study, normotensive individuals also presented increased endothelium-dependent vasodilation. No alterations in the response to isosorbide dinitrate - an endothelium-independent vasodilator - were observed after training in both groups.</p>
      <p>Individuals with acute myocardial infarction undergoing a 3-month aerobic exercise training (cycle ergometer) at an intensity of 75% of the peak exercise heart rate also presented an increase in endothelium-dependent vasodilation. However, one month after detraining the benefits disappeared<sup>18</sup>. This result suggests that even individuals with a history of a cardiac event may obtain improvement of the endothelial function.</p>
      <p>Goto et al<sup>11</sup> analyzed the effect of different intensities of aerobic exercise on the arteries, and verified that moderate intensity (50% VO<sub>2 Max</sub>) was the only one able to improve the endothelium-dependent vasodilation. Low (25% VO<sub>2 Max</sub>) and high intensity exercise (75% VO<sub>2 Max</sub>) did not provide the endothelial function with any benefit. As regards high intensity, it was responsible for an increase in the oxidative stress, a harmful aspect to the arterial wall. For this reason, moderate intensity seems to be more appropriate for sedentary individuals who seek cardiovascular benefits through regular aerobic exercise.</p>
      <p>Although studies state that regular aerobic exercise is responsible for the change in endothelium-dependent vasodilation, a key question arises within this context. How much does the aerobic fitness respond to these changes?</p>
      <p>Cardiorespiratory fitness proved to be related to a slower progression of atherosclerosis in men<sup>19</sup>. However, the association of cardiorespiratory fitness and endothelium-dependent vasodilation has been little studied.</p>
      <p>Higher aerobic exercise capacity (VO<sub>2 Max</sub>)<sup>20</sup> was associated with greater arterial diameter (r=0.66, p&lt;0.002) during hyperemic response in trained elderly men (68.5 &#177; 2.3 years) in comparison with sedentary elderly men (64.7 &#177; 1.4 years). This association results from a higher endothelium-dependent vasodilation ability in individuals who trained at least 3X/week for at least 1h/day.</p>
      <p>This result raises the possibility that the aerobic exercise capacity is being preferably related to the endothelial function, because this is a much more accurate measurement. Quite the opposite, training programs are subject to lack of attendance, lack of compliance, and to the individual physiologic response to the training itself, because these variables cannot be completely controlled in exercise programs.</p>
      <p>Although studies with children and adolescents are not common, Watts et al<sup>21</sup> found a positive result in normalization of the circulatory function in obese adolescents using a circuit training program that consisted of a cycle ergometer and resisted training. Additionally, an increase in the functional capacity, muscle force and improvement in the body composition of these adolescents were observed. Studies reported that prevention of cardiovascular diseases should begin at childhood, because the risk factors are already present in this phase<sup>22</sup>.</p>
      <p>It seems that even with differences in the exercises and intensity used, the studies have demonstrated that aerobic exercise is able to improve and restore the endothelium-dependent vasodilation.</p>
      <p>
        <bold>Aerobic exercise and intima-media thickness</bold>
      </p>
      <p>Intima-media thickness is one of the stages of atherosclerosis, and, consequently, its assessment can be helpful in the diagnosis and prognosis of the atherogenic process<sup>5</sup>. Rosfors et al<sup>23</sup> verified that the intima-media thickness was related to the degree of atherosclerosis in the carotid bifurcation. Zureik et al<sup>6</sup> also verified that a high intima-media thickness predicted the occurrence of atherosclerotic plaques in elderly individuals.</p>
      <p>Although not significantly, studies relating the intima-media thickness to training programs and types of training have been conducted.</p>
      <p>Rauramaa et al<sup>24</sup> did not verify any reduction in the intima-media thickness of middle-aged men (whether or not treated with statins) who underwent a 6-year moderate aerobic exercise program and were analyzed with a carotid bifurcation ultrasonography (10 MHZ). However, when a subgroup of individuals not taking statins was analyzed separately, exercise was proven to be efficient in the reduction of the atherosclerotic progression. Thus, the authors concluded that the medication may have masked the effects of exercises on this population. Nonetheless, divergent opinions regarding Rauramaa et al's study have been recently published by authors in this field<sup>25,26</sup>.</p>
      <p>Dinenno et al<sup>27</sup> conducted a study with two distinct moments, consisting of a cross-sectional analysis and an aerobic training intervention. The authors verified the influence of the aerobic training on arterial remodeling. In the first moment, the authors analyzed 55 endurance-exercise trained men (47 &#177; 2 years) and 53 sedentary men (47 &#177; 2 years). Endurance-trained individuals were demonstrated to have a common femoral artery lumen diameter 7% greater than sedentary individuals. Additionally, the intima-media thickness and the intima-media/lumen ratio of the individuals trained was 16% and 21% lower, respectively. For the intervention study, the authors selected 22 individuals (51 &#177; 2 years) from the sedentary group, who underwent a 3-month aerobic training. The individuals exercised 13.5 &#177; 1.0 weeks, 5.3 &#177; 0.3 days, 45 &#177; 2 min. per session, on average, at 73 &#177; 1% of the maximum HR. After the training period, a 9% increase in the common femoral artery lumen diameter was observed, along with a reduction by 14% and 20% in the intima-media thickness and in the intima-media/lumen ratio, respectively.</p>
      <p>However, in a later study, these authors did not find a positive result of aerobic exercises in the reduction of arterial hardening. The 3-month training program was not significantly efficient in the promotion of arterial benefits. In this study, a positive relationship between age and intima-media thickness ratio was found. Thus, exercise was not able to prevent the consequences of aging.</p>
      <p>Dinenno et al<sup>29</sup> reported that age-associated arterial wall thickening is closely related to elevations in sympathetic activity.</p>
      <p>Moreau et al<sup>30</sup> analyzed postmenopausal women and verified that both hormone replacement therapy and regular aerobic exercises were associated with a lower intima-media thickness ratio. In addition to the classification of individuals into sedentary or trained, the maximum aerobic capacity was also used to divide the groups. Together, hormone replacement therapy and regular aerobic exercises promoted greater changes in the intima-media thickness than each one separately. However, both the regular aerobic exercise group and the hormone replacement group were able to promote significant changes in the intima-media thickness when compared to the sedentary group not treated with hormone replacement.</p>
      <p>Because of some controversy on the effects of the aerobic exercise on the intima-media thickness, further investigation on the subject is necessary so as to verify whether exercise is really efficient to restore the arterial integrity in this stage of atherosclerosis.</p>
      <p>
        <bold>Effects of aerobic exercise on atherosclerotic risk factors</bold>
      </p>
      <p>Although endothelium-dependent vasodilation and arterial thickness indexes are excellent indicators of arterial integrity, several risk factors act on the development of cardiovascular diseases. A decrease in risk factors should be promoted to prevent and control atherosclerosis<sup>31</sup>.</p>
      <p>Aerobic training is an excellent tool to modify risk factors (<xref ref-type="fig" rid="figura2-body2">Figure 2</xref>). As demonstrated by Rique et al<sup>32</sup>, changes in life habits, such as nutrition and regular practice of physical exercises, may lead to a reduction in cardiovascular risk factors. Exercise can attenuate dyslipidemias, diabetes, obesity and hypertension.</p>
      <fig id="figura2-body2">
        <graphic xlink:href="1678-4170-abc-87-05-e226-00036-gf02-en.jpg"/></fig>
      <p>Dyslipidemia is mainly characterized by high levels of LDL-C and triglycerides, and low levels of HDL-C<sup>1,2,12,33</sup>. Exercise is a tool used to modify the lipid profile, and significantly increases the levels of serum HDL-C and reduces serum LDL-C and triglycerides. In a meta-analysis, Kelley and Kelley<sup>34</sup> demonstrated that aerobic exercise (<underline>&gt;</underline>8 weeks) is able to significantly increase the levels of HDL<sub>2</sub>-C in adults (<underline>&gt;</underline>18 years).</p>
      <p>Roberts et al.<sup>35</sup> verified that aerobic exercise for three weeks improved blood pressure, oxidative stress, nitric oxide availability and the metabolic profile. Lalonde et al<sup>36</sup> observed that the more intense intervention (strict diet with exercises) provided better results in relation to the effects on the lipid profile and quality of life than the less intense interventions (diet, strict diet without exercise). Diet associated with exercise provided a higher reduction of LDL-C, and an increase of HDL-C.</p>
      <p>Couillard et al<sup>37</sup> verified that a 20-week endurance exercise training was more effective in increasing HDL-C in individuals with high levels of triglycerides and low levels of HDL-C than in individuals with normal levels of triglycerides and low levels of HDL-C.</p>
      <p>Bhalodkar et al<sup>38</sup> analyzed a group of Asian Indians and verified that the group which exercised regularly presented the best levels of HDL-C in the large subclass. Additionally, the size of HDL-C particles was significantly larger in the active group in comparison with the inactive group.</p>
      <p>Matos and Ladeia<sup>39</sup> studied a rural community and verified that normal serum triglyceride levels and a normal waist-hip ratio (WHR) were related to a higher energy expenditure and a better risk profile.</p>
      <p>Another worldwide problem is obesity, which is a secondary risk factor, although extremely related to the atherosclerotic process. Yet, central (abdominal) obesity is a better predictor of heart diseases than overall obesity. Pitanga and Lessa<sup>40</sup> demonstrated that waist circumference (W) and waist-hip ratio (WHR) are more appropriate than BMI to discriminate high coronary risks.</p>
      <p>Lakka et al<sup>41</sup> found a relation between abdominal obesity (high waist circumference and high waist-hip ratio) and development of atherosclerosis, regardless of overall obesity and other risk factors. The major factor for this relation is that abdominal obesity is directly linked to visceral fat, which is, in turn, an indicator of unfavorable metabolic effects. These effects result in insulin resistance, glucose intolerance, hypertriglyceridemia, elevation of LDL-C levels, reduction in HDL-C levels, and others.</p>
      <p>Kretschmer et al<sup>42</sup> conducted a study in Wistars rats and demonstrated that a 5-week aerobic exercise program was effective in maintaining and reducing the body weight of the rats. Because of the type of analysis of this study (post-mortem), the results are highly reliable, since fat quantification becomes much more precise.</p>
      <p>Savage et al.<sup>43</sup> verified that a 4-month training program consisting of walking long duration (60-90 min) 5 to 7 days per week at an intensity of 50-60% of peak VO<sub>2</sub> was effective in reducing body weight (-4.6 kg) in overweight coronary patients. In addition to body weight, there was a reduction of fat percentage (-2.9%), subcutaneous adipose tissue (-12%), and visceral adipose tissue (-14%). Concurrently, lipid profile changes could also be observed, the main of which was a reduction by 23.7% in triglyceride levels.</p>
      <p>Another risk factor for the development of atherosclerosis is diabetes, even in asymptomatic individuals<sup>44,45</sup>. The main reason for that is the irregular glucose metabolism in diabetics, and, consequently, an accelerated fat metabolism in this population<sup>46</sup>.</p>
      <p>Nishida et al.<sup>47</sup> verified that a 12-week training (60 minutes daily, 5 days/week) at lactate threshold intensity improved insulin sensitivity. This sensitivity resulted mainly in improved peripheral insulin sensitivity and peripheral glucose effectiveness. However, the effects of training were verified to be lost one week after detraining.</p>
      <p>Short et al<sup>48</sup> verified that a 4-month aerobic training improved insulin sensitivity in younger individuals, but not in middle-aged and elderly individuals. Yet, benefits regarding mitochondrial content and aerobic capacity were observed in all age ranges.</p>
      <p>Hypertension seems to be one of the major risk factors for the development of atherosclerosis, because it is closely related to the triggering of arterial wall inflamation<sup>49</sup> . This inflammation affects the normal artery vasodilation and promotes a systematic increase in systolic and diastolic blood pressure, thus triggering a vicious cycle<sup>12</sup>.</p>
      <p>Studies correlating reduction of blood pressure with the practice of aerobic exercises have been frequently conducted. The most stable responses of blood pressure to exercises may be observed after 1-10 weeks of training<sup>50</sup>.</p>
      <p>The American College of Sports Medicine (ACSM)<sup>51</sup> established patterns for exercise intensity aiming at reducing blood pressure, stating that hypertensive individuals should practice moderate exercises at a 40-60% VO<sub>2</sub><sub>max</sub>. This is, therefore, a 10% reduction in relation to the 1993 position stand. As regards exercise time, approximately 30 continuous or accumulated minutes or more of moderate daily exercises are recommended. The ACSM explains that blood pressure reduction occurs by means of several factors, including reduction of the sympathetic nervous activity; reduction of the renin-angiotensin system action; improved vascular responsiveness; increased capillarization; increased arterial lumen, and others.</p>
      <p>Moreira et al<sup>52</sup> verified that aerobic training at two different intensities (20% and 60% of the maximum workload) in a cycle ergometer for 10 weeks provided similar results in the reduction of ambulatory blood pressure.</p>
      <p>Takata et al<sup>53</sup> found a positive relation between physical activity and blood pressure reduction. The study was conducted among 207 untreated subjects with stage 1 and 2 essential hypertension. The researchers divided the subjects into groups based on the weekly activity level: sedentary control, 30-60 min/week, 61-90 min/week, 91-120 min/week, and &gt; 120 min/week. The analysis was made at the end of an 8-week program. The results showed that those who exercised had systolic and diastolic pressure reductions, and that the control group did not present any change in these pressures. The 61-90 min/week group obtained better results than the 30-60 min/week group. No greater reductions were observed for the groups with further increases in exercise volume.</p>
      <p>Therefore, aerobic exercise promotes a significant reduction of cardiovascular risk factors, as observed in the studies described. Thus, aerobic exercise may be used in risk populations with the purpose of decreasing the prevalence of cardiovascular diseases.</p>
      <p>
        <bold>Inflammation markers and response to aerobic exercise</bold>
      </p>
      <p>Technological progress has led to the investigation of inflammation or atherogenic markers of chronic and acute exercise. Ers&#246;z et al<sup>54</sup> found increased collagen-induced platelet aggregation in submaximal exercise. When maximal incremental exercise was performed, the same increased collagen and ADP-induced platelet aggregation was verified, in addition to increased levels of thromboxane B<sub>2.</sub> In Duncan et al's study<sup>55</sup>, individuals who trained at high intensity and high frequency showed higher levels of serum homocysteine, although with a reduction of fasting insulin.</p>
      <p>Killewich et al.<sup>56</sup> found positive results in a 6-month endurance training on fibrinolytic activity, in subjects with intermittent claudication. Exercise proved to be efficient on the reduction of plasminogen activator inhibitor-1 (PAI-1), and on the increase of tissue plasminogen activator (tPA), therefore, an increased fibrinolytic activity. Endurance training proved to be efficient in the treatment of peripheral arterial disease in this study.</p>
      <p>
        <bold>Recommendations</bold>
      </p>
      <p>Currently, the differentiation between physical activity and physical exercise is evident. The first consists of any bodily movement resulting in energy expenditure beyond resting levels. Exercise, in turn, is a subset of physical activity that is planned, structured and repetitive with the purpose of improving or maintaining physical fitness. Despite these differences, it seems reasonable to suggest the practice of physical activity as a means of modifying sedentary habits of the population, and as a preparation for engaging in a program of physical exercises.</p>
      <p>The American Heart Association (AHA)<sup>57</sup> has a recommendation for the practice of physical activities in the prevention of atherosclerosis (Table 1). This recommendation in based on the ACSM position stand on physical activity<sup>58</sup>, which has been adopted worldwide by the majority of the programs related to this issue. With the adoption of this recommendation, it is possible to reduce the frequency of heart diseases and risk factors, as well as to change the lipid profile.</p>
      <p>For a higher adhesion to the recommendations, both the AHA and the ACSM suggest the performance of daily activities, such as gardening, climbing flights of stairs, walking, bicycle riding, etc. Minimum duration of each activity bout should be 10 minutes. Thus, three bouts of10 minutes each can be performed during the day. Peterson et al<sup>59</sup> found identical results as regards calorie expenditure with 30 continuous minutes and with three bouts of 10 minutes. Yet, further research is necessary to verify differences regarding changes in risk factors in these two types of situations.</p>
      <p>
        <bold>Conclusion</bold>
      </p>
      <p>We can observe, therefore, that aerobic exercise has demonstrated to be efficient in the prevention of atherosclerosis, and to be able to restore the normal endothelial function and attenuate risk factors in several studies mentioned. Moderate intensity seems to be the most appropriate to prevent atherosclerosis. Additionally, physical activity seems to be a great strategy to start changing sedentary habits, as well as preparing the individual to engage in a physical exercise program.</p>
      <p>Although the majority of the studies show the benefits of aerobic exercise on atherosclerosis, further investigation on the subject is necessary to better explain the underlying physiological mechanisms.</p>
      <p>
        <graphic xlink:href="1678-4170-abc-87-05-e226-00036-e01-en.jpg"/></p>
      <p>
        <bold>Refer&#234;ncias</bold>
      </p>
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      <p>10. Willmore JH, Costill DL. Physiology of Sport and Exercise. 2nd Ed. Champaign (IL): Human Kinetics: 1999.</p>
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      <p>12. Da luz PL, Laurindo FRM, Chagas ACP. Endot&#233;lio: Doen&#231;as Cardiovasculares. 1ed. S&#227;o Paulo, SP: Atheneu, 2004.</p>
      <p>13. DeSouza CA, Shapiro LF, Clevenger CM, Dinneno FA, Monahan KD, Tanaka H, Seals D. Regular Aerobic Exercise Prevents and Restores Age-Related Declines in Endothelium-Dependent Vasodilation in Healthy Men. Circulation. 2000; 102: 1351-1357.</p>
      <p>14. Galleta F, Franzoni F, Virdis A, et al. Endothelium-dependent vasodilation and carotid artery wall remodeling wall in athletes and sedentary subjects. Atherosclerosis. 2005; In press: 1-9.</p>
      <p>15. Clarkson P, Montgomery HE, Mullen MJ, Donald AE, Powe AJ, Bull T, et al. Exercise training enhances endothelium function in young men. J Am Coll Cardiol. 1999;33(5): 1379-85.</p>
      <p>16. Gokce N, Vita JA, Bader DS, Sherman DL, Hunter LM, Holbrook M, et al. Effect of exercise on upper and lower extremity endothelium function in patients with coronary artery disease. Am J Cardiol. 2002; 90: 124-7.</p>
      <p>17. Higashi Y, Sasaki S, Kurisu S, et al. Regular aerobic exercise augments endothelium-dependent vascular relaxation in normotensive as well as hypertensive subjects role of endothelium-derived oxide nitric oxide. Circulation. 1999; 100: 1194-1202.</p>
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      <p>
        <fn id="back-body2" fn-type="corresp">
          <p>
            <graphic xlink:href="1678-4170-abc-87-05-e226-00036-e02-en.jpg"/></p>
          <p>
            <bold>Mailing Address:</bold>
          </p>
          <p> Jeffer Eidi Sasaki</p>
          <p> Rua Baltazar Carrasco dos Reis, 908</p>
          <p> 80215-160 &#150; Curitiba, PR</p>
          <p> E-mail: </p>
          <p>
            <email xlink:href="jeffersasaki@gmail.com">jeffersasaki@gmail.com</email>
          </p>
        </fn>
      </p>
      <p>Recebido em 25/10/05; revisado recebido em 20/03/06; aceito em 30/03/06.</p>
      <p>Outro problema de propor&#231;&#227;o mundial &#233; a obesidade, que se constitui em um fator de risco secund&#225;rio, no entanto extremamente ligado ao processo ateroscler&#243;tico. Ainda assim, a obesidade central (abdominal) &#233; um melhor preditor para doen&#231;as do cora&#231;&#227;o do que a obesidade geral. Pitanga &amp; Lessa<sup>40</sup> demonstraram que os &#237;ndices circunfer&#234;ncia de cintura (C) e raz&#227;o circunfer&#234;ncia cintura quadril (RCCQ) s&#227;o mais apropriados do que o IMC para discrimina&#231;&#227;o dos riscos coronarianos elevados.</p>
    </body>
  </sub-article>
</article>
