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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">S8DD5kZsqfZQNkBgjkzFPbT</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v2">S0066-782X2012000600012</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v1">S0066-782X(12)09800612</article-id>
      <article-id pub-id-type="doi">10.1590/S0066-782X2012000600012</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Artigo de Revis&#227;o</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Escore de c&#225;lcio e angiotomografia coronariana na estratifica&#231;&#227;o do risco cardiovascular</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Azevedo</surname>
            <given-names>Clerio F.</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
          <xref ref-type="aff" rid="aff02"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Rochitte</surname>
            <given-names>Carlos E.</given-names>
          </name>
          <xref ref-type="aff" rid="aff03"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Lima</surname>
            <given-names>Jo&#227;o A.C.</given-names>
          </name>
          <xref ref-type="aff" rid="aff04"/>
        </contrib>
      </contrib-group>
      <aff id="aff01">
        <addr-line>
          <named-content content-type="state"/>
        </addr-line>
        <institution content-type="orgname">Instituto D'Or</institution>
        <country country="BR">Brazil</country>
      </aff>
      <aff id="aff02">
        <addr-line>
          <named-content content-type="city">Rio de Janeiro</named-content>
          <named-content content-type="state">Rio de Janeiro</named-content>
        </addr-line>
        <institution content-type="orgname">Universidade do Estado do Rio de Janeiro</institution>
        <country country="BR">Brazil</country>
      </aff>
      <aff id="aff04">
        <addr-line>
          <named-content content-type="state"/>
        </addr-line>
        <institution content-type="orgname">Johns Hopkins University</institution>
        <country country="US">United States</country>
      </aff>
      <aff id="aff03">
        <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>2012</year>
      </pub-date>
      <volume>98</volume>
      <issue>6</issue>
      <fpage>559</fpage>
      <lpage>568</lpage>
      <history>
        <date date-type="received">
          <day>28</day>
          <month>02</month>
          <year>2012</year>
        </date>
        <date date-type="accepted">
          <day>15</day>
          <month>03</month>
          <year>2012</year>
        </date>
        <date date-type="rev-recd">
          <day>28</day>
          <month>02</month>
          <year>2012</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>A doen&#231;a cardiovascular representa a principal causa de mortalidade no mundo. A capacidade de identificar, dentre os indiv&#237;duos assintom&#225;ticos, o subgrupo que apresenta maior risco de desenvolver eventos cardiovasculares no futuro representa uma etapa fundamental em qualquer estrat&#233;gia voltada para a diminui&#231;&#227;o da taxas de eventos cardiovasculares. O primeiro passo na estratifica&#231;&#227;o do risco cardiovascular &#233; a utiliza&#231;&#227;o dos "escores de risco global", dentre os quais o mais frequentemente utilizado &#233; o escore de Framingham. Entretanto, estudos pr&#233;vios demonstraram que embora muito &#250;teis, os escores cl&#237;nicos, quando utilizados isoladamente, apresentam capacidade limitada de estratifica&#231;&#227;o do risco cardiovascular em uma parcela significativa da popula&#231;&#227;o. &#201; nesse contexto que o escore de c&#225;lcio (EC) coronariano e a angiotomografia das art&#233;rias coron&#225;rias podem desempenhar papel importante como ferramentas complementares na estratifica&#231;&#227;o de risco dos pacientes assintom&#225;ticos. O EC coronariano proporciona importantes informa&#231;&#245;es progn&#243;sticas que s&#227;o incrementais aos escores cl&#237;nicos baseados nos fatores de risco tradicionais e a outras modalidades diagn&#243;sticas, como a dosagem da prote&#237;na C reativa, por exemplo. Al&#233;m disso, o EC tamb&#233;m tem o potencial de alterar a conduta e auxiliar no manejo cl&#237;nico dos pacientes. J&#225; a angiotomografia coronariana proporciona avalia&#231;&#227;o detalhada da anatomia das art&#233;rias coron&#225;rias, permitindo visualizar n&#227;o apenas o l&#250;men, mas tamb&#233;m as paredes arteriais coronarianas. Comparada &#224; coronariografia invasiva convencional, a angiotomografia apresenta excelente acur&#225;cia para identificar e, principalmente, excluir a presen&#231;a de les&#245;es obstrutivas significativas. Adicionalmente, demonstrou-se capaz de proporcionar informa&#231;&#245;es progn&#243;sticas incrementais aos fatores de risco tradicionais e ao EC coronariano.</p>
      </abstract>
      <kwd-group xml:lang="pt" kwd-group-type="author-generated">
        <kwd>Medi&#231;&#227;o de risco</kwd>
        <kwd>angiografia Coron&#225;ria</kwd>
        <kwd>doen&#231;a das coron&#225;rias</kwd>
        <kwd>tomografia computadorizada por raios x</kwd>
      </kwd-group>
      <pub-date publication-format="electronic" date-type="pub">
        <day>08</day>
        <month>08</month>
        <year>2012</year>
      </pub-date>
    </article-meta>
  </front>
  <body>
    <p>
      <bold>ARTIGO DE REVIS&#195;O</bold>
    </p>
    <p>Escore de c&#225;lcio e angiotomografia coronariana na estratifica&#231;&#227;o do risco cardiovascular</p>
    <p>
      <bold>Clerio F. Azevedo<sup>I, II</sup>; Carlos E. Rochitte<sup>III</sup>; Jo&#227;o A.C. Lima<sup>IV</sup></bold>
    </p>
    <p><sup>I</sup>Instituto D'Or de Pesquisa e Ensino (IDOR) </p>
    <p><sup>II</sup>Universidade do Estado do Rio de Janeiro Rio de Janeiro, RJ </p>
    <p><sup>III</sup>Instituto do Cora&#231;&#227;o (InCor) da Faculdade de Medicina da Universidade de S&#227;o Paulo, S&#227;o Paulo, SP, Brasil </p>
    <p><sup>IV</sup>Johns Hopkins University, Estados Unidos, USA</p>
    <p>
      <xref ref-type="corresp" rid="back">Endere&#231;o para correspond&#234;ncia</xref>
    </p>
    <p>
      <bold>RESUMO</bold>
    </p>
    <p>A doen&#231;a cardiovascular representa a principal causa de mortalidade no mundo. A capacidade de identificar, dentre os indiv&#237;duos assintom&#225;ticos, o subgrupo que apresenta maior risco de desenvolver eventos cardiovasculares no futuro representa uma etapa fundamental em qualquer estrat&#233;gia voltada para a diminui&#231;&#227;o da taxas de eventos cardiovasculares. O primeiro passo na estratifica&#231;&#227;o do risco cardiovascular &#233; a utiliza&#231;&#227;o dos "escores de risco global", dentre os quais o mais frequentemente utilizado &#233; o escore de Framingham. Entretanto, estudos pr&#233;vios demonstraram que embora muito &#250;teis, os escores cl&#237;nicos, quando utilizados isoladamente, apresentam capacidade limitada de estratifica&#231;&#227;o do risco cardiovascular em uma parcela significativa da popula&#231;&#227;o. </p>
    <p> &#201; nesse contexto que o escore de c&#225;lcio (EC) coronariano e a angiotomografia das art&#233;rias coron&#225;rias podem desempenhar papel importante como ferramentas complementares na estratifica&#231;&#227;o de risco dos pacientes assintom&#225;ticos. O EC coronariano proporciona importantes informa&#231;&#245;es progn&#243;sticas que s&#227;o incrementais aos escores cl&#237;nicos baseados nos fatores de risco tradicionais e a outras modalidades diagn&#243;sticas, como a dosagem da prote&#237;na C reativa, por exemplo. Al&#233;m disso, o EC tamb&#233;m tem o potencial de alterar a conduta e auxiliar no manejo cl&#237;nico dos pacientes. J&#225; a angiotomografia coronariana proporciona avalia&#231;&#227;o detalhada da anatomia das art&#233;rias coron&#225;rias, permitindo visualizar n&#227;o apenas o l&#250;men, mas tamb&#233;m as paredes arteriais coronarianas. Comparada &#224; coronariografia invasiva convencional, a angiotomografia apresenta excelente acur&#225;cia para identificar e, principalmente, excluir a presen&#231;a de les&#245;es obstrutivas significativas. Adicionalmente, demonstrou-se capaz de proporcionar informa&#231;&#245;es progn&#243;sticas incrementais aos fatores de risco tradicionais e ao EC coronariano.</p>
    <p><bold>Palavras-chave:</bold> Medi&#231;&#227;o de risco; angiografia Coron&#225;ria; doen&#231;a das coron&#225;rias; tomografia computadorizada por raios x.</p>
    <p>
      <bold>Introdu&#231;&#227;o</bold>
    </p>
    <p>A doen&#231;a cardiovascular representa a principal causa de mortalidade no mundo. Em apenas um ano, ocorrem 17,3 milh&#245;es de mortes causadas por doen&#231;as cardiovasculares, das quais 7,3 milh&#245;es secund&#225;rias &#224; doen&#231;a ateroscler&#243;tica coronariana (DAC) e 6,2 milh&#245;es secund&#225;rias a doen&#231;as vasculares cerebrais<sup>1</sup>. S&#243; no Brasil ocorrem mais de 900.000 casos de infarto agudo do mioc&#225;rdio (IAM) por ano, com mais de 300.000 casos fatais<sup>2</sup>. A redu&#231;&#227;o desses n&#250;meros, e a consequente diminui&#231;&#227;o da morbidade e mortalidade relacionadas &#224; DAC, tem sido um dos principais objetivos das pol&#237;ticas de sa&#250;de p&#250;blica no Brasil e no mundo. Entretanto, sabe-se que mais da metade das s&#237;ndromes coronarianas agudas e mortes s&#250;bitas ocorrem em indiv&#237;duos previamente assintom&#225;ticos<sup>3</sup>. Portanto, a capacidade de identificar, dentre os indiv&#237;duos assintom&#225;ticos, o subgrupo que apresenta maior risco de desenvolver eventos cardiovasculares no futuro representa uma etapa fundamental em qualquer estrat&#233;gia voltada para a diminui&#231;&#227;o da taxas de eventos cardiovasculares<sup>4</sup>.</p>
    <p>O primeiro passo na estratifica&#231;&#227;o do risco cardiovascular de indiv&#237;duos assintom&#225;ticos &#233; a utiliza&#231;&#227;o dos "escores de risco global", dentre os quais os escores de Framingham, PROCAM (<italic>M&#252;nster Heart Study)</italic>, SCORE, Reynolds, etc. Destes, o escore de Framingham &#233; o mais frequentemente utilizado. Esse tipo de avalia&#231;&#227;o &#233; relativamente simples de ser realizada, n&#227;o traz riscos aos pacientes, proporciona informa&#231;&#245;es progn&#243;sticas valiosas e possui grande potencial de alterar a conduta cl&#237;nica. Portanto, os escores de avalia&#231;&#227;o do risco global devem ser sempre realizados como primeiro passo na estratifica&#231;&#227;o do risco cardiovascular dos indiv&#237;duos assintom&#225;ticos<sup>5</sup>.</p>
    <p>Mas uma quest&#227;o fundamental &#233; a seguinte: a utiliza&#231;&#227;o apenas dos escores cl&#237;nicos &#233; suficiente? O fato &#233; que estudos pr&#233;vios demonstraram que esses escores tamb&#233;m apresentam limita&#231;&#245;es. Segundo Greenland e cols.<sup>3</sup>, 50% dos pacientes com s&#237;ndromes coronarianas agudas teriam sido classificados como risco intermedi&#225;rio pelo escore de Framingham se tivessem sido avaliados antes do evento agudo<sup>3</sup>. Nesse mesmo estudo, os autores demonstraram que cerca de 40% da popula&#231;&#227;o geral tamb&#233;m seria classificada no grupo de risco intermedi&#225;rio. Sobretudo, eles demonstraram que 75% dos pacientes com s&#237;ndromes coronarianas agudas previamente assintom&#225;ticos n&#227;o preenchiam crit&#233;rios para tratamento com estatinas antes do evento agudo.</p>
    <p>Esses dados ilustram o conceito de que, embora muito &#250;teis, os escores cl&#237;nicos, quando utilizados isoladamente, apresentam capacidade limitada de estratifica&#231;&#227;o do risco cardiovascular em uma parcela significativa da popula&#231;&#227;o. De fato, essas limita&#231;&#245;es s&#227;o ainda mais significativas nos indiv&#237;duos mais jovens e naqueles do sexo feminino. &#201; exatamente nesse contexto que alguns exames laboratoriais e de imagem, dentre os quais o escore de c&#225;lcio (EC) coronariano e a angiotomografia das art&#233;rias coron&#225;rias, podem desempenhar papel importante como ferramentas complementares aos escores cl&#237;nicos na estratifica&#231;&#227;o de risco dos pacientes assintom&#225;ticos.</p>
    <p>O advento recente da tomografia computadorizada (TC) com m&#250;ltiplos detectores vem causando uma verdadeira revolu&#231;&#227;o nas estrat&#233;gias de investiga&#231;&#227;o diagn&#243;stica e progn&#243;stica em cardiologia<sup>6-11</sup>. A avalia&#231;&#227;o da anatomia e da carga ateroscler&#243;tica coronariana, antes apenas poss&#237;vel atrav&#233;s de exames invasivos (coronariografia invasiva, ultrassom intracoronariano, etc.), agora pode ser obtida de forma n&#227;o invasiva e com excelente acur&#225;cia por meio da TC card&#237;aca. Na pr&#225;tica, a utiliza&#231;&#227;o da TC para avalia&#231;&#227;o da DAC pode se dar de duas formas principais: atrav&#233;s da determina&#231;&#227;o do EC coronariano e atrav&#233;s da angiotomografia coronariana propriamente dita.</p>
    <p>Embora a angiotomografia apresente excelente acur&#225;cia para identificar ou excluir a presen&#231;a de les&#245;es obstrutivas significativas, e seja capaz de proporcionar valiosas informa&#231;&#245;es progn&#243;sticas<sup>6</sup>, a modalidade diagn&#243;stica mais robusta e validada para estratificar o risco cardiovascular global &#233; o EC coronariano<sup>5,12,13</sup>.</p>
    <p>Nesta revis&#227;o, abordaremos as no&#231;&#245;es t&#233;cnicas b&#225;sicas, as aplica&#231;&#245;es cl&#237;nicas principais e as evid&#234;ncias cient&#237;ficas dispon&#237;veis sobre os dois m&#233;todos: o EC e a angiotomografia coronariana, focando principalmente nos seus pap&#233;is como ferramentas na estratifica&#231;&#227;o do risco cardiovascular global.</p>
    <p>
      <bold>Escore de c&#225;lcio coronariano</bold>
    </p>
    <p>
      <bold>O exame</bold>
    </p>
    <p>Inicialmente, antes do advento dos aparelhos de TC com m&#250;ltiplos detectores, o m&#233;todo utilizado para avalia&#231;&#227;o do EC coronariano era a tomografia computadorizada por emiss&#227;o de feixe de el&#233;trons (<italic>Electron-beam computed tomography</italic>). De fato, boa parte da literatura cient&#237;fica acumulada sobre EC coronariano &#233; baseada nessa t&#233;cnica<sup>14</sup>. Entretanto, atualmente, a TC por emiss&#227;o de feixe de el&#233;trons representa uma modalidade diagn&#243;stica ultrapassada e virtualmente indispon&#237;vel em nosso meio. Com a introdu&#231;&#227;o da TC com m&#250;ltiplos detectores no final da d&#233;cada de 90, este passou a ser o m&#233;todo utilizado para avalia&#231;&#227;o do EC coronariano na pr&#225;tica cl&#237;nica, revelando-se pelo menos compar&#225;vel e, em muitos aspectos, superior &#224; TC por emiss&#227;o de feixe de el&#233;trons para este fim.</p>
    <p>Portanto, neste cap&#237;tulo, todas as considera&#231;&#245;es t&#233;cnicas sobre a aquisi&#231;&#227;o das imagens de EC se referem &#224; TC com m&#250;ltiplos detectores.</p>
    <p>A determina&#231;&#227;o do EC coronariano se baseia em uma aquisi&#231;&#227;o n&#227;o contrastada de uma s&#233;rie de cortes axiais com 3 mm de espessura cobrindo toda a extens&#227;o do cora&#231;&#227;o. As imagens s&#227;o adquiridas de forma sincronizada ao sinal do eletrocardiograma (ECG). O protocolo de sincroniza&#231;&#227;o ao ECG pode ser do tipo prospectivo ou retrospectivo. A dose de radia&#231;&#227;o utilizada nos protocolos de aquisi&#231;&#227;o retrospectiva &#233; significativamente maior, portanto, os protocolos prospectivos s&#227;o os mais utilizados. Na pr&#225;tica, a dose efetiva de radia&#231;&#227;o em uma aquisi&#231;&#227;o prospectiva &#233; baixa, em geral abaixo de 1,5 mSv, e, em m&#233;dia, cerca de 0,9 a 1,1 mSv.</p>
    <p>A calcifica&#231;&#227;o &#233; definida como uma les&#227;o hiperatenuante com intensidade de sinal acima de 130 unidades Hounsfield (HU) e &#225;rea <underline>&gt;</underline> 3 pixels adjacentes (pelo menos 1 mm<sup>2</sup>). Pode ser calculada a partir da soma ponderada das densidades acima de 130 HU (escore de Agatston) ou por m&#233;todos que determinam o volume ou massa de c&#225;lcio. Ainda que os escores de volume ou massa de c&#225;lcio apresentem melhor reprodutibilidade, os grandes bancos de dados populacionais que descrevem a distribui&#231;&#227;o da calcifica&#231;&#227;o coronariana de acordo com a idade, etnia e sexo dos pacientes, s&#227;o baseadas no escore de Agatston e, portanto, este &#233; o mais utilizado na pr&#225;tica cl&#237;nica (<xref ref-type="fig" rid="f01">Figura 1</xref>).</p>
    <p content-type="asset">
      <fig id="f01">
        <graphic xlink:href="1678-4170-abc-98-06-0559-00012-gf01.jpg"/></fig>
    </p>
    <p>Resta a pergunta: Como s&#227;o classificados e interpretados os resultados do EC coronariano?</p>
    <p>Existem duas formas de se classificar os valores de EC obtidos: utilizando-se pontos de corte fixos ou pontos de corte ajustados para a idade, o sexo e, mais recentemente, a etnia do paciente. Os valores limites mais aceitos nos dois tipos de classifica&#231;&#227;o est&#227;o descritos na <xref ref-type="table" rid="t1">tabela 1</xref>.</p>
    <table-wrap id="t1">
      <graphic xlink:href="1678-4170-abc-98-06-0559-00012-gt01.jpg"/></table-wrap>
    <p>Na classifica&#231;&#227;o por pontos de corte fixos, os pacientes s&#227;o categorizados de acordo com limites pr&#233;-estabelecidos. J&#225; na classifica&#231;&#227;o por pontos de cortes ajustados, os pacientes s&#227;o categorizados de acordo com os percentis de distribui&#231;&#227;o dos valores de EC da popula&#231;&#227;o geral (<xref ref-type="fig" rid="f02">Fig. 2</xref>). &#201; importante salientar, entretanto, que ambas as formas de classifica&#231;&#227;o proporcionam informa&#231;&#245;es progn&#243;sticas valiosas e que, de uma forma geral, ambas est&#227;o presentes nos laudos emitidos nos centros diagn&#243;sticos capacitados na realiza&#231;&#227;o de exames de imagem cardiol&#243;gicos.</p>
    <p content-type="asset">
      <fig id="f02">
        <graphic xlink:href="1678-4170-abc-98-06-0559-00012-gf02.jpg"/></fig>
    </p>
    <p>Inicialmente, o EC coronariano foi utilizado como uma ferramenta diagn&#243;stica com o objetivo de identificar ou excluir a presen&#231;a de DAC obstrutiva em pacientes sintom&#225;ticos. Esses estudos iniciais demonstraram que o EC apresenta &#243;timo valor preditivo negativo (VPN) para excluir a presen&#231;a de DAC significativa (96% a 100%), mas que o valor preditivo positivo (VPP) era, no m&#225;ximo, moderado<sup>14</sup>. Em contraste, estudos mais recentes demonstraram que, particularmente em pacientes mais jovens ou em popula&#231;&#245;es com alta preval&#234;ncia de DAC significativa, al&#233;m do VPP positivo inadequado, o EC tamb&#233;m apresenta VPN insuficiente para excluir a presen&#231;a de doen&#231;a obstrutiva significativa.</p>
    <p>De fato, Gottlieb e cols.<sup>15</sup> demonstraram que, em uma popula&#231;&#227;o com 56% de preval&#234;ncia de DAC significativa, at&#233; mesmo 19% dos pacientes com EC = 0 apresentavam pelo menos uma les&#227;o obstrutiva <underline>&gt;</underline> 50% na coronariografia invasiva<sup>15</sup>. Considerando-se o VPP apenas moderado e os dados conflitantes em rela&#231;&#227;o ao VPN, o conceito atual &#233; de que, de uma forma geral, o EC coronariano n&#227;o deve ser utilizado como uma ferramenta para o diagn&#243;stico da DAC obstrutiva significativa em pacientes sintom&#225;ticos. Como veremos a seguir, o real valor do EC coronariano na pr&#225;tica cl&#237;nica consiste em sua capacidade de proporcionar valiosas informa&#231;&#245;es progn&#243;sticas e servir como importante ferramenta na estratifica&#231;&#227;o do risco de pacientes assintom&#225;ticos.</p>
    <p>
      <bold>Valor progn&#243;stico</bold>
    </p>
    <p>Um conceito importante para se entender porque o EC coronariano tem o potencial de desempenhar relevante papel na estratifica&#231;&#227;o do risco cardiovascular &#233; o de que a calcifica&#231;&#227;o coronariana representa um marcador da presen&#231;a de placas ateroscler&#243;ticas nas art&#233;rias coron&#225;rias. No leito arterial coronariano, a calcifica&#231;&#227;o ocorre quase que exclusivamente no contexto da doen&#231;a ateroscler&#243;tica. Em um dado indiv&#237;duo, a quantidade de calcifica&#231;&#227;o presente nas art&#233;rias coron&#225;rias apresenta boa correla&#231;&#227;o com a carga ateroscler&#243;tica coronariana total. Entretanto, nem toda placa ateroscler&#243;tica &#233; calcificada. De fato, relatos pr&#233;vios demonstraram que a por&#231;&#227;o calcificada corresponde apenas a cerca de 20% do volume total da placa; ou seja, a calcifica&#231;&#227;o coronariana representaria apenas a "ponta do <italic>iceberg</italic>" da DAC; com a por&#231;&#227;o n&#227;o calcificada respondendo por cerca de 80% da carga ateroscler&#243;tica total.</p>
    <p>&#201; importante ressaltar ainda que a presen&#231;a ou aus&#234;ncia de c&#225;lcio n&#227;o est&#225; associada de forma significativa com o grau de propens&#227;o que uma determinada placa tem de romper, e que a presen&#231;a de calcifica&#231;&#227;o n&#227;o &#233; um sinal de "estabilidade" e nem de "instabilidade" de uma placa qualquer.</p>
    <p>Diversos estudos populacionais longitudinais, que inclu&#237;ram grande n&#250;mero de pacientes, demonstraram que o EC coronariano apresenta associa&#231;&#227;o significativa com a ocorr&#234;ncia de eventos cardiovasculares maiores (morte por todas as causas, morte card&#237;aca e IAM n&#227;o fatal) no acompanhamento de m&#233;dio e longo prazo. Quanto maior a quantidade de c&#225;lcio nas coron&#225;rias, maior a chance do paciente apresentar um evento cardiovascular no futuro.</p>
    <p>Ainda mais importante, uma s&#233;rie de estudos pr&#233;vios demonstrou que a capacidade do EC em predizer a ocorr&#234;ncia de eventos cardiovasculares &#233; adicional &#224; estratifica&#231;&#227;o do risco pelo escore de Framingham e a outros m&#233;todos tamb&#233;m utilizados para estratificar o risco, como a dosagem da prote&#237;na C reativa, por exemplo. De fato, um estudo cl&#225;ssico<sup>16</sup> demonstrou que os pacientes com risco intermedi&#225;rio pelo escore de Framingham e com EC &gt; 300 apresentaram uma taxa de eventos cardiovasculares de 2,8%/ano (aproximadamente equivalente a uma taxa de 28% em 10 anos), o que os colocaria no grupo de alto risco (&gt; 20% em 10 anos).</p>
    <p>Um consenso recente publicado pelo ACCF/AHA sobre o uso do EC coronariano na avalia&#231;&#227;o do risco cardiovascular global<sup>12</sup> examinou os dados combinados de seis grandes estudos que inclu&#237;ram 27.622 pacientes assintom&#225;ticos e avaliou os principais preditores de um total de 395 eventos cardiovasculares. Dentre os 11.815 pacientes com EC = 0, a taxa de eventos foi muito baixa, apenas 0,4% nos 3 a 5 anos subsequentes. Comparados com os pacientes com EC = 0, aqueles com EC entre 100 e 400 apresentaram um risco relativo (RR) de 4,3 (intervalo de confian&#231;a de 95% [IC 95%] de 3,5 a 5,2; p &lt; 0,0001), aqueles com EC entre 400 e 1000 apresentaram um RR de 7,2 (IC 95% de 5,2 a 9,9; p &lt; 0,0001), e aqueles com EC &gt; 1000 apresentaram um RR de 10,8 (IC 95% de 4,2 a 27,7; p &lt; 0,0001).</p>
    <p>Desde a publica&#231;&#227;o desse consenso, outros estudos prospectivos confirmaram tais achados e demonstraram que a associa&#231;&#227;o entre EC e progn&#243;stico &#233; semelhante independentemente do sexo ou da etnia do paciente<sup>14,17</sup>. Ainda mais importante, todos esses estudos tamb&#233;m confirmaram que a avalia&#231;&#227;o do EC &#233; capaz de proporcionar informa&#231;&#245;es progn&#243;sticas incrementais &#224; avalia&#231;&#227;o dos fatores de risco tradicionais apenas. Na an&#225;lise ROC, a &#225;rea sob a curva para predizer a ocorr&#234;ncia de eventos cardiovasculares foi significativamente maior com o EC coronariano do que com os escores de Framingham ou PROCAM. No estudo MESA, a estat&#237;stica "C", considerando-se apenas os fatores de risco tradicionais, foi de 0,79 para predizer eventos cardiovasculares maiores, e de 0,83 quando a informa&#231;&#227;o do EC foi associada aos fatores de risco (p = 0,006)<sup>17</sup>.</p>
    <p>Estudos pr&#233;vios tamb&#233;m demonstraram que o EC coronariano proporciona informa&#231;&#245;es progn&#243;sticas adicionais &#224; avalia&#231;&#227;o da prote&#237;na C reativa. Em quatro estudos baseados em modelos multivariados, o EC permaneceu como um preditor independente de eventos cardiovasculares maiores, enquanto a prote&#237;na C reativa deixou de ser um preditor significativo nas an&#225;lises multivariadas<sup>18-21</sup>. Quando comparado &#224; medida da espessura da camada &#237;ntima/m&#233;dia da car&#243;tida (IMT), o EC coronariano revelou ser um melhor preditor de eventos subsequentes; o <italic>hazard ratio</italic> (HR) do IMT foi de 1,7 (IC 95% de 1,1 a 2,7; p = 0,07), enquanto o HR do EC foi de 8,2 (IC 95% de 4,5 a 15,1; p = 0,001)<sup>22</sup>.</p>
    <p>
      <bold>Potencial de alterar a conduta cl&#237;nica</bold>
    </p>
    <p>Al&#233;m do seu papel como ferramenta de estratifica&#231;&#227;o do risco, outro aspecto importante relacionado ao EC coronariano diz respeito ao seu potencial valor como instrumento capaz de alterar a conduta cl&#237;nica e auxiliar no manejo dos pacientes com suspeita de DAC. Em um estudo observacional, Kalia e cols.<sup>23</sup> demonstraram que a taxa de uso de medica&#231;&#245;es hipolipemiantes em pacientes com dislipidemia aumentou de 44% para mais de 90% naqueles que apresentavam calcifica&#231;&#227;o acentuada na avalia&#231;&#227;o pelo EC<sup>23</sup>. Outras medidas comportamentais preventivas, tais como exerc&#237;cios f&#237;sicos regulares e ado&#231;&#227;o de dietas mais saud&#225;veis, tamb&#233;m apresentaram melhora no subgrupo com maiores valores de EC. Sobretudo, em um estudo prospectivo que acompanhou 1.640 pacientes por uma m&#233;dia de seis anos, as taxas de uso de estatinas e aspirina foram, respectivamente, 3,5 e 3 vezes maiores no subgrupo com placas de calcifica&#231;&#227;o no EC<sup>24</sup>. Esse aumento significativo foi independente de outros fatores de risco e demonstrou o potencial do EC coronariano em alterar a conduta cl&#237;nica numa amostra de indiv&#237;duos representativos da popula&#231;&#227;o geral.</p>
    <p>De acordo com os resultados do estudo JUPITER<sup>25</sup>, um grande n&#250;mero de pacientes assintom&#225;ticos com valores de LDL considerados normais passou a ter indica&#231;&#227;o de tratamento com estatinas. Nesse estudo, o principal crit&#233;rio para indicar o tratamento com estatinas foi a dosagem da prote&#237;na C reativa ultrassens&#237;vel. Entretanto, dados recentes do estudo MESA demonstraram que o subgrupo de pacientes com indica&#231;&#227;o de estatinas segundo os crit&#233;rios do JUPITER, mas que n&#227;o possu&#237;am calcifica&#231;&#227;o coronariana na avalia&#231;&#227;o pelo EC, apresentaram um baixo risco de eventos cardiovasculares no acompanhamento evolutivo. Dado que, no estudo JUPITER, a redu&#231;&#227;o de risco absoluto considerando-se a popula&#231;&#227;o com um todo foi baixa, os autores do estudo MESA conclu&#237;ram que o EC coronariano pode ter um papel relevante na sele&#231;&#227;o, dentre os pacientes que preenchem os crit&#233;rios para receberem estatinas, daqueles com maior potencial de se beneficiar do tratamento. Em outras palavras, n&#227;o apenas a prote&#237;na C reativa, mas a combina&#231;&#227;o desta com o EC coronariano, seria a melhor estrat&#233;gia para selecionar os pacientes com maior potencial de se beneficiar do tratamento com estatinas.</p>
    <p>
      <bold>Recomenda&#231;&#245;es atuais</bold>
    </p>
    <p>Em um consenso de especialistas sobre o uso do EC coronariano na avalia&#231;&#227;o do risco cardiovascular global, publicado pelo ACCF/AHA em 2007<sup>12</sup>, pacientes assintom&#225;ticos com risco intermedi&#225;rio pelo escore de Framingham foram considerados bons candidatos &#224; avalia&#231;&#227;o pelo EC com o objetivo de refinar a estratifica&#231;&#227;o e, potencialmente, alterar a conduta cl&#237;nica. Nesse documento, os autores n&#227;o classificaram o grau de recomenda&#231;&#227;o.</p>
    <p>Mais recentemente, no <italic>Guideline</italic> sobre a avalia&#231;&#227;o do risco cardiovascular de pacientes assintom&#225;ticos, publicado pelo ACCF/AHA em 2010<sup>5</sup>, a quantifica&#231;&#227;o do EC coronariano para estratificar o risco cardiovascular em indiv&#237;duos com risco intermedi&#225;rio pelo escore de Framingham foi considerada uma indica&#231;&#227;o classe IIa, n&#237;vel de evid&#234;ncia B. &#201; importante ressaltar que em tal documento as &#250;nicas interven&#231;&#245;es consideradas como classe I foram a estratifica&#231;&#227;o utilizando escores de risco globais baseados nos fatores de riscos tradicionais, como o escore de Framingham, por exemplo, e a avalia&#231;&#227;o cl&#237;nica quanto &#224; presen&#231;a de hist&#243;ria familiar de DAC precoce. Nenhum exame diagn&#243;stico, seja ele de imagem ou laboratorial, foi classificado com grau de recomenda&#231;&#227;o classe I.</p>
    <p>S&#243; como base de compara&#231;&#227;o, nesse documento, a realiza&#231;&#227;o do ecocardiograma, do teste ergom&#233;trico, ou da cintilografia de perfus&#227;o mioc&#225;rdica foram considerados como indica&#231;&#245;es com graus de recomenda&#231;&#227;o IIb ou III.</p>
    <p>Finalmente, no documento do ACCF/SCCT/ACR/AHA/ASE/ASNC/NASCI/SCAI/SCMR sobre os crit&#233;rios de uso apropriado da TC card&#237;aca publicado em 2010<sup>8</sup>, a utiliza&#231;&#227;o do EC coronariano para estratifica&#231;&#227;o do risco cardiovascular global em pacientes com risco intermedi&#225;rio pelo escore de Framingham foi definida como uma indica&#231;&#227;o apropriada n&#237;vel 7 (A7), em uma escala que varia de 1 a 9, sendo que os n&#237;veis 1-3 correspondem a indica&#231;&#245;es n&#227;o apropriadas, os n&#237;veis 4-6 a indica&#231;&#245;es incertas e os n&#237;veis 7-9 a indica&#231;&#245;es apropriadas. Nesse documento, a utiliza&#231;&#227;o do EC coronariano tamb&#233;m foi considerada uma indica&#231;&#227;o apropriada n&#237;vel 7 (A7) em pacientes com baixo risco pelo escore de Framingham, mas que tinham hist&#243;ria familiar de DAC precoce.</p>
    <p>Com rela&#231;&#227;o &#224;s recomenda&#231;&#245;es nacionais, a Diretriz da Sociedade Brasileira de Cardiologia sobre o uso da TC card&#237;aca publicada em 2006<sup>7</sup> definiu como uma indica&#231;&#227;o classe I a realiza&#231;&#227;o do EC coronariano para estratificar o risco cardiovascular global em pacientes com risco intermedi&#225;rio pelo escore de Framingham. Esse mesmo documento definiu como uma indica&#231;&#227;o classe IIa a utiliza&#231;&#227;o do EC em pacientes com baixo risco mas com hist&#243;ria familiar de DAC precoce.</p>
    <p>
      <bold>Angiotomografia Coronariana</bold>
    </p>
    <p>
      <bold>O exame</bold>
    </p>
    <p>A realiza&#231;&#227;o da angiotomografia coronariana s&#243; se tornou poss&#237;vel com o advento dos aparelhos de TC com m&#250;ltiplos detectores no final da d&#233;cada de 90. Passou a ser clinicamente utilizada a partir do in&#237;cio da d&#233;cada seguinte, ap&#243;s a introdu&#231;&#227;o dos tom&#243;grafos com 16 fileiras de detectores. Desde ent&#227;o, o desenvolvimento tecnol&#243;gico nessa &#225;rea tem sido vertiginoso e, atualmente, j&#225; existem dispon&#237;veis equipamentos com 256 e at&#233; 320 fileiras de detectores, que permitem a aquisi&#231;&#227;o de todas as imagens necess&#225;rias para a avalia&#231;&#227;o coronariana em um &#250;nico batimento card&#237;aco.</p>
    <p>A angiotomografia coronariana baseia-se na aquisi&#231;&#227;o de uma s&#233;rie de cortes axiais com espessura submilim&#233;trica cobrindo toda a extens&#227;o do cora&#231;&#227;o. Assim como no caso do EC, as imagens s&#227;o adquiridas de forma sincronizada ao sinal do ECG. O protocolo de sincroniza&#231;&#227;o ao ECG pode ser do tipo prospectivo sequencial ou retrospectivo helicoidal. Considerando-se os aparelhos de 64 canais atualmente dispon&#237;veis, enquanto a quantidade de radia&#231;&#227;o de uma aquisi&#231;&#227;o retrospectiva com modula&#231;&#227;o de dose situa-se em torno de 9,0 mSv, a dose efetiva de uma aquisi&#231;&#227;o prospectiva gira em torno de 3,0 mSv<sup>26</sup>.</p>
    <p>S&#243; como base de compara&#231;&#227;o, a dose de radia&#231;&#227;o de uma cintilografia mioc&#225;rdica convencional com tecn&#233;cio ou sestamibi tamb&#233;m se situa em torno de 9,0 mSv. A de uma cintilografia mioc&#225;rdica com t&#225;lio gira em torno de 18,0 mSv. Cabe ressaltar que, de uma forma geral, tem havido um grande esfor&#231;o por parte da comunidade m&#233;dica no sentido de reduzir cada vez mais a quantidade de radia&#231;&#227;o utilizada nos exames cardiol&#243;gicos e que os atuais aparelhos com <underline>&gt;</underline> 256 canais j&#225; permitem a realiza&#231;&#227;o da angiotomografia coronariana com doses efetivas de radia&#231;&#227;o inferiores a 1,0 mSv.</p>
    <p>
      <bold>Valor diagn&#243;stico</bold>
    </p>
    <p>J&#225; existem algumas revis&#245;es sistem&#225;ticas examinando o valor diagn&#243;stico da angiotomografia coronariana a partir do advento dos aparelhos de 64 canais em 2004<sup>27-30</sup>. De uma forma geral, esses estudos demonstram que a acur&#225;cia diagn&#243;stica do m&#233;todo melhorou &#224; medida que a tecnologia evoluiu dos aparelhos de 4 e 16 canais para os atuais aparelhos de 64 canais. Da mesma forma, o n&#250;mero de segmentos coronarianos n&#227;o analis&#225;veis diminuiu com o progresso do desenvolvimento tecnol&#243;gico. Baseado nessas conclus&#245;es, estabeleceu-se o conceito de que, embora a aplica&#231;&#227;o cl&#237;nica do m&#233;todo tenha sido poss&#237;vel a partir dos aparelhos com 16 canais, o estado da arte atual em rela&#231;&#227;o aos exames de angiotomografia coronariana exige o uso de aparelhos com 64 ou mais canais, principalmente devido &#224; sua maior cobertura longitudinal e melhor resolu&#231;&#227;o espacial e temporal (<xref ref-type="fig" rid="f03">Fig. 3</xref>).</p>
    <p content-type="asset">
      <fig id="f03">
        <graphic xlink:href="1678-4170-abc-98-06-0559-00012-gf03.jpg"/></fig>
    </p>
    <p>Atualmente existem mais de 50 estudos unic&#234;ntricos<sup>29</sup> e tr&#234;s multic&#234;ntricos<sup>31-33</sup> examinando a acur&#225;cia da angiotomografia coronariana com aparelhos de 64 canais na avalia&#231;&#227;o de pacientes sintom&#225;ticos est&#225;veis com suspeita de DAC significativa. Em todos os casos, a angiotomografia foi comparada com o m&#233;todo de refer&#234;ncia atual, a coronariografia invasiva convencional. De uma maneira geral, esses estudos demonstraram de forma bastante consistente que a angiotomografia apresenta excelente acur&#225;cia para detectar ou excluir a presen&#231;a de DAC significativa. Em particular, eles demonstraram que o VPN &#233; especialmente alto, tornando o exame particularmente &#250;til para excluir a presen&#231;a de les&#245;es obstrutivas significativas nessa popula&#231;&#227;o.</p>
    <p>Na revis&#227;o sistem&#225;tica mais recente, que avaliou os estudos unic&#234;ntricos realizados at&#233; o final de 2007 utilizando aparelhos de 64 canais<sup>29</sup>, a sensibilidade m&#233;dia para identificar a presen&#231;a de DAC significativa foi de 98% e a especificidade m&#233;dia foi de 88%. A preval&#234;ncia m&#233;dia de DAC significativa nesses estudos foi de 61% e os VPP E VPN foram 93% e 96%, respectivamente.</p>
    <p>No estudo multic&#234;ntrico CORE 64<sup>32</sup>, que avaliou 291 pacientes com indica&#231;&#227;o cl&#237;nica de coronariografia invasiva, a preval&#234;ncia de DAC significativa foi de 56%. Nesse estudo, a sensibilidade e a especificidade da angiotomografia coronariana, em uma an&#225;lise por paciente, foram 85% e 90%, respectivamente. A &#225;rea sob a curva ROC foi de 0,93. O VPP foi de 91% e o VPN foi de 83%.</p>
    <p>No estudo multic&#234;ntrico ACCURACY<sup>31</sup>, que avaliou 245 pacientes sintom&#225;ticos, a preval&#234;ncia DAC significativa foi de 25% para estenoses <underline>&gt;</underline> 50% e de apenas 14% para estenoses <underline>&gt;</underline> 70%. Nesse estudo, a sensibilidade foi de 94% ou 95%, dependendo do limiar escolhido para definir a presen&#231;a de DAC significativa. A especificidade foi de 82%. O VPN foi de 99%, tanto para o limiar de 50% como para o de 70%. J&#225; o VPP foi de apenas 48% considerando-se o limiar de 70%, e de 64% considerando-se o de 50%.</p>
    <p>Finalmente, em um estudo multic&#234;ntrico realizado em tr&#234;s hospitais universit&#225;rios holandeses, foram avaliados 360 pacientes com indica&#231;&#227;o de coronariografia invasiva<sup>33</sup>. A preval&#234;ncia de DAC significativa foi de 68%. A sensibilidade e a especificidade da angiotomografia coronariana, em uma an&#225;lise por paciente, foram de 100% e de 64%, respectivamente. O VPP foi de 86% e o VPN foi de 97%.</p>
    <p>
      <bold>Valor progn&#243;stico</bold>
    </p>
    <p>Nos &#250;ltimos anos, um grande n&#250;mero de estudos tem avaliado o papel da resson&#226;ncia magn&#233;tica e da TC n&#227;o apenas na avalia&#231;&#227;o diagn&#243;stica<sup>13,31-39</sup>, mas tamb&#233;m na avalia&#231;&#227;o progn&#243;stica<sup>40-47</sup> dos pacientes portadores de doen&#231;as cardiovasculares. No caso da tomografia card&#237;aca, uma s&#233;rie de estudos recentes demonstrou que n&#227;o apenas a avalia&#231;&#227;o do EC, mas tamb&#233;m a avalia&#231;&#227;o da anatomia coronariana pela angiotomografia coronariana proporciona informa&#231;&#245;es progn&#243;sticas importantes nos pacientes com suspeita de DAC significativa<sup>42,44,45,47-49</sup>. Utilizando um aparelho de TCMD de 16 canais, Min e cols<sup>44</sup>. estudaram 1.127 pacientes e avaliaram a rela&#231;&#227;o entre mortalidade por todas as causas e os resultados da angiotomografia coronariana. Ap&#243;s um seguimento m&#233;dio de 15 meses, os autores demonstraram que a gravidade da DAC pela angiotomografia foi um fator preditor importante da mortalidade total dos pacientes, proporcionando informa&#231;&#245;es progn&#243;sticas adicionais aos fatores de risco tradicionais.</p>
    <p>Em outro importante estudo, Ostrom e cols.<sup>45</sup> avaliaram 2.538 pacientes atrav&#233;s da angiotomografia coronariana utilizando um aparelho de TC por emiss&#227;o de feixe de el&#233;trons<sup>45</sup>. Ap&#243;s um seguimento m&#233;dio de 78 meses, os autores demonstraram que a angiotomografia apresenta valor progn&#243;stico incremental n&#227;o apenas aos fatores de risco tradicionais, mas tamb&#233;m &#224; avalia&#231;&#227;o do EC coronariano. Posteriormente, van Werkhoven e cols.<sup>49</sup> avaliaram 541 pacientes utilizando tanto a angiotomografia coronariana como a cintilografia de perfus&#227;o mioc&#225;rdica. Ap&#243;s um seguimento m&#233;dio de 22 meses avaliando o desfecho combinado de morte card&#237;aca, infarto n&#227;o fatal e hospitaliza&#231;&#227;o por angina inst&#225;vel, os autores demonstraram que tanto a avalia&#231;&#227;o anat&#244;mica pela angiotomografia quanto a avalia&#231;&#227;o funcional pela cintilografia de perfus&#227;o proporcionam informa&#231;&#245;es progn&#243;sticas importantes e que o valor progn&#243;stico dos dois m&#233;todos &#233; adicional um ao outro.</p>
    <p>Em um estudo recente, Azevedo e cols.<sup>48</sup> avaliaram 529 pacientes com suspeita de DAC obstrutiva que haviam sido submetidos a testes de isquemia com resultados inconclusivos. Eles demonstraram que cerca de 70% desses pacientes n&#227;o apresentavam les&#245;es obstrutivas significativas. De fato, cerca de 40% apresentavam art&#233;rias coron&#225;rias completamente normais, com EC zero. Sobretudo, ap&#243;s um seguimento m&#233;dio de 30 meses, os autores demonstraram que tanto o escore de c&#225;lcio como a angiotomografia coronariana proporcionam importantes informa&#231;&#245;es progn&#243;sticas nessa popula&#231;&#227;o.</p>
    <p>Tamb&#233;m recentemente, Hadamitzky e cols.<sup>42</sup> acompanharam 2.223 pacientes com suspeita de DAC, por um per&#237;odo m&#233;dio de 28 meses, e confirmaram os achados dos estudos anteriores, demonstrando que a angiotomografia coronariana n&#227;o apenas proporciona informa&#231;&#245;es progn&#243;sticas importantes, mas tamb&#233;m que essas s&#227;o incrementais aos escores de risco cl&#237;nicos e ao EC coronariano<sup>42</sup>. Na an&#225;lise ROC, a &#225;rea sob a curva para predizer a ocorr&#234;ncia de eventos cardiovasculares foi de 0,79 para o escore cl&#237;nico apenas, de 0,84 para o escore cl&#237;nico + EC e de 0,89 para o escore cl&#237;nico + EC + angiotomografia (p &lt; 0,001).</p>
    <p>
      <bold>Caracteriza&#231;&#227;o da placa ateroscler&#243;tica</bold>
    </p>
    <p>Uma caracter&#237;stica importante da angiotomografia coronariana, que a distingue da coronariografia invasiva, &#233; a sua capacidade de proporcionar, al&#233;m da visualiza&#231;&#227;o da luz do vaso, tamb&#233;m a avalia&#231;&#227;o das paredes arteriais coronarianas. Dessa forma, permite n&#227;o apenas identificar as les&#245;es que estejam causando obstru&#231;&#227;o luminal, mas tamb&#233;m caracterizar as placas ateroscler&#243;ticas de uma forma geral, obstrutivas ou n&#227;o obstrutivas. De fato, diversos estudos pr&#233;vios demonstraram que o volume das placas medido pela angiotomografia apresentou boa correla&#231;&#227;o com as medidas obtidas pelo padr&#227;o ouro atual, o ultrassom intracoron&#225;rio<sup>50</sup>.</p>
    <p>Ainda mais importante, relatos recentes sugerem que a caracteriza&#231;&#227;o das placas ateroscler&#243;ticas pela angiotomografia tem o potencial auxiliar na identifica&#231;&#227;o dos pacientes mais vulner&#225;veis a apresentar um evento coronariano agudo. Motoyama e cols.<sup>51</sup> avaliaram 1.059 pacientes quanto &#224; presen&#231;a de dois par&#226;metros medidos pela angiotomografia coronariana: o grau de remodelamento positivo e a presen&#231;a de &#225;reas de baixa atenua&#231;&#227;o na placa (sugerindo conte&#250;do lip&#237;dico)<sup>51</sup>. O tempo m&#233;dio de acompanhamento foi de 27 meses. A taxa de eventos cardiovasculares nos 45 pacientes com os dois par&#226;metros presentes foi de 22,2%. Em contraste, a taxa observada nos pacientes com apenas um par&#226;metro foi de 3,7% e naqueles sem nenhum par&#226;metro presente foi de 0,4%.</p>
    <p>&#201; importante salientar, entretanto, que a utiliza&#231;&#227;o da angiotomografia com o objetivo de caracterizar as placas ateroscler&#243;ticas e identificar aquelas com sinais sugestivos de vulnerabilidade ainda n&#227;o representa uma indica&#231;&#227;o clinicamente estabelecida e, atualmente, encontra-se apenas no campo do desenvolvimento experimental.</p>
    <p>
      <bold>Conclus&#227;o</bold>
    </p>
    <p>Atualmente, a utiliza&#231;&#227;o da TC para avalia&#231;&#227;o da DAC pode se dar de duas formas principais: atrav&#233;s da determina&#231;&#227;o do EC coronariano e atrav&#233;s da angiotomografia coronariana propriamente dita. O EC coronariano proporciona importantes informa&#231;&#245;es progn&#243;sticas que s&#227;o incrementais aos escores cl&#237;nicos baseados nos fatores de risco tradicionais e a outras modalidades diagn&#243;sticas, como a dosagem da prote&#237;na C reativa, por exemplo. Al&#233;m disso, o EC tamb&#233;m tem o potencial de alterar a conduta e auxiliar no manejo cl&#237;nico dos pacientes. Portanto, a realiza&#231;&#227;o do EC coronariano est&#225; indicada quando o objetivo for a estratifica&#231;&#227;o do risco cardiovascular global de pacientes assintom&#225;ticos com risco intermedi&#225;rio pelo escore de Framingham.</p>
    <p>J&#225; a angiotomografia coronariana proporciona avalia&#231;&#227;o detalhada da anatomia das art&#233;rias coron&#225;rias, permitindo visualizar n&#227;o apenas o l&#250;men, mas tamb&#233;m as paredes arteriais coronarianas. Comparada &#224; coronariografia invasiva convencional, a angiotomografia apresenta excelente acur&#225;cia para identificar e, principalmente, excluir a presen&#231;a de les&#245;es obstrutivas significativas. Adicionalmente, demonstrou-se capaz de proporcionar informa&#231;&#245;es progn&#243;sticas incrementais aos fatores de risco tradicionais e ao EC coronariano. N&#227;o obstante, embora represente ferramenta diagn&#243;stica muito &#250;til e esteja indicada na avalia&#231;&#227;o diagn&#243;stica de pacientes sintom&#225;ticos com suspeita de DAC, atualmente, a angiotomografia coronariana ainda n&#227;o est&#225; indicada quando o objetivo for apenas a estratifica&#231;&#227;o do risco cardiovascular global de pacientes assintom&#225;ticos.</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>N&#227;o h&#225; vincula&#231;&#227;o deste estudo a programas de p&#243;s-gradua&#231;&#227;o.</p>
    <p>
      <fn id="back" fn-type="corresp">
        <p>Endere&#231;o para correspond&#234;ncia:</p>
        <p> Carlos Eduardo Rochitte </p>
        <p> Resson&#226;ncia &amp; Tomografia Cardiovascular </p>
        <p> Av. Dr. En&#233;as de Carvalho Aguiar 44 - Andar AB - Cerqueira Cesar </p>
        <p> 05403-000 - S&#227;o Paulo, SP - Brasil </p>
        <p> E-mail: </p>
        <p><email xlink:href="rochitte@cardiol.br">rochitte@cardiol.br</email>, </p>
        <p>
          <email xlink:href="rochitte@incor.usp.br">rochitte@incor.usp.br</email>
        </p>
      </fn>
    </p>
    <p>Artigo recebido em 28/02/12 </p>
    <p> Revisado em 28/02/12 </p>
    <p> Aceito em 15/03/12</p>
  </body>
  <back>
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          <volume>54</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Motoyama</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Sarai</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Harigaya</surname>
              <given-names>H</given-names>
            </name>
            <name>
              <surname>Anno</surname>
              <given-names>H</given-names>
            </name>
            <name>
              <surname>Inoue</surname>
              <given-names>K</given-names>
            </name>
            <name>
              <surname>Hara</surname>
              <given-names>T</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
    </ref-list>
  </back>
  <sub-article article-type="translation" id="TRen" xml:lang="en">
    <front-stub>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Review Article</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title xml:lang="en">Coronary artery calcium score and coronary computed tomographic angiography for cardiovascular risk stratification</article-title>
      </title-group>
      <abstract xml:lang="en">
        <p>Cardiovascular disease is the leading mortality cause worldwide. The capacity to identify among the asymptomatic individuals the subgroup at greater risk for developing cardiovascular events is fundamental in any strategy aimed at reducing the rate of cardiovascular events. The first step in cardiovascular risk stratification is the use of global risk scores, the Framingham risk score being the most frequently used. However, previous studies have shown that, although very useful, clinical scores, when used alone, have a limited capacity for stratifying cardiovascular risk in a significant part of the population. In that context, coronary artery calcium score (CACS) and coronary computed tomographic angiography might play an important role as complementary tools for risk stratification of asymptomatic patients. The CACS provides important prognostic information that is incremental to clinical scores based on traditional risk factors and other diagnostic modalities, such as C-reactive protein measurement. In addition, CACS has the potential to change and help the patients' clinical management. On the other hand, coronary computed tomographic angiography provides a detailed assessment of the anatomy of the coronary arteries, allowing visualizing not only the lumen, but also the coronary arterial walls. Compared with conventional invasive coronary angiography, coronary computed tomographic angiography has excellent accuracy to identify and mainly exclude the presence of significant obstructive lesions. In addition, it proved to be able to provide incremental prognostic information to traditional risk factors and CACS.</p>
      </abstract>
      <kwd-group xml:lang="en">
        <kwd>Calcium</kwd>
        <kwd>risk assessment</kwd>
        <kwd>coronary angiography</kwd>
        <kwd>coronary disease</kwd>
        <kwd>tomography</kwd>
        <kwd>x ray computed</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <p>
        <bold>REVIEW ARTICLE</bold>
      </p>
      <p><undefined id="top-body2"/>Coronary artery calcium score and coronary computed tomographic angiography for cardiovascular risk stratification</p>
      <p>
        <bold>Clerio F. Azevedo<sup>I, II</sup>; Carlos E. Rochitte<sup>III</sup>; Jo&#227;o A.C. Lima<sup>IV</sup></bold>
      </p>
      <p><sup>I</sup>Instituto D'Or de Pesquisa e Ensino (IDOR)</p>
      <p><sup>II</sup>Universidade do Estado do Rio de Janeiro Rio de Janeiro, RJ</p>
      <p><sup>III</sup>Instituto do Cora&#231;&#227;o (InCor) da Faculdade de Medicina da Universidade de S&#227;o Paulo, S&#227;o Paulo, SP, Brasil</p>
      <p><sup>IV</sup>Johns Hopkins University, Estados Unidos, USA</p>
      <p>Correspondence to </p>
      <p>
        <bold>ABSTRACT</bold>
      </p>
      <p>Cardiovascular disease is the leading mortality cause worldwide. The capacity to identify among the asymptomatic individuals the subgroup at greater risk for developing cardiovascular events is fundamental in any strategy aimed at reducing the rate of cardiovascular events. The first step in cardiovascular risk stratification is the use of global risk scores, the Framingham risk score being the most frequently used. However, previous studies have shown that, although very useful, clinical scores, when used alone, have a limited capacity for stratifying cardiovascular risk in a significant part of the population.</p>
      <p> In that context, coronary artery calcium score (CACS) and coronary computed tomographic angiography might play an important role as complementary tools for risk stratification of asymptomatic patients. The CACS provides important prognostic information that is incremental to clinical scores based on traditional risk factors and other diagnostic modalities, such as C-reactive protein measurement. In addition, CACS has the potential to change and help the patients' clinical management. On the other hand, coronary computed tomographic angiography provides a detailed assessment of the anatomy of the coronary arteries, allowing visualizing not only the lumen, but also the coronary arterial walls. Compared with conventional invasive coronary angiography, coronary computed tomographic angiography has excellent accuracy to identify and mainly exclude the presence of significant obstructive lesions. In addition, it proved to be able to provide incremental prognostic information to traditional risk factors and CACS.</p>
      <p><bold>Keywords:</bold> Calcium / analysis; risk assessment; coronary angiography; coronary disease; tomography; x ray computed.</p>
      <p>
        <bold>Introduction</bold>
      </p>
      <p>Cardiovascular disease is the leading mortality cause worldwide. In only one year, 17.3 million individuals died due to cardiovascular diseases, 7.3 million secondary to coronary artery disease (CAD) and 6.2 million secondary to cerebrovascular diseases<sup>1</sup>. Only in Brazil, over 900,000 cases of acute myocardial infarction (AMI) occurred per year, of which over 300,000 were fatal<sup>2</sup>. Reducing those numbers and, consequently, the CAD-related morbidity and mortality has been one of the major objectives of public health policies in Brazil and worldwide. However, more than half of the acute coronary syndromes and sudden deaths are known to occur in previously asymptomatic individuals<sup>3</sup>. Thus, the capacity to identify among asymptomatic individuals the subgroup at greater risk for developing cardiovascular events represents a fundamental step in any strategy aimed at reducing the rate of cardiovascular events<sup>4</sup>.</p>
      <p>The first step in the cardiovascular risk stratification of asymptomatic individuals is the use of global risk scores, such as the Framingham, PROCAM (M&#252;nster Heart Study), SCORE, and Reynolds risk scores, of which, the Framingham risk score is the most frequently used. That type of assessment is relatively simple to be performed, bears no risk for patients, provides valuable prognostic information and bears a great potential to change clinical management. Thus, global risk assessment scores should be always the first step in cardiovascular risk stratification of asymptomatic individuals<sup>5</sup>.</p>
      <p>A fundamental question is whether using only clinical scores suffices. Previous studies have shown that those scores have limitations. According to Greenland et al<sup>3</sup>, 50% of the patients with acute coronary syndromes would have been classified as at intermediate risk by use of the Framingham score if they had been assessed before the acute event<sup>3</sup>. In that same study, the authors have shown that approximately 40% of the general population would also be classified as at intermediate risk. In addition, they have shown that 75% of the previously asymptomatic patients with acute coronary syndromes had not met the criteria for treatment with statins before the acute event.</p>
      <p>Those data illustrate the concept that, although very useful, the clinical scores, when used alone, have a limited capacity for stratifying the cardiovascular risk in a significant part of the population. In fact, such limitations are even more significant in younger individuals and those of the female sex. It is exactly in that context that some laboratory and imaging tests, such as coronary artery calcium score (CACS) and coronary computed tomographic angiography (CCTA), might play an important role as complementary tools to clinical scores for risk stratification of asymptomatic patients.</p>
      <p>The recent advent of multidetector computed tomography (CT) has revolutionized the strategies of diagnostic and prognostic investigation in cardiology<sup>6-11</sup>. The assessment of the coronary artery anatomy and atherosclerotic burden, previously only possible by use of invasive exams, such as invasive coronary angiography and intracoronary ultrasound, can now be obtained in a non-invasive way and with excellent accuracy by use of cardiac CT. In clinical practice, CT can be used to assess CAD in determining CACS and in CCTA.</p>
      <p>Although CCTA has excellent accuracy to identify or exclude the presence of significant obstructive lesions, being able to provide valuable prognostic information<sup>6</sup>, the most robust and validated diagnostic modality to stratify global cardiovascular risk is CACS<sup>5,12,13</sup>.</p>
      <p>This review approaches the basic technical notions, major clinical applications and scientific evidence available on both methods, CACS and CCTA, focusing mainly on their roles as tools for global cardiovascular risk stratification.</p>
      <p>
        <bold>Coronary artery calcium score</bold>
      </p>
      <p>
        <bold>The test</bold>
      </p>
      <p>Initially, prior to the advent of multidetector CT devices, electron-beam CT was used to assess CACS. In fact, a good part of the scientific literature on CACS has been based on that technique<sup>14</sup>. However, currently, electron-beam CT represents an outdated and virtually unavailable diagnostic modality. With the introduction of multidetector CT devices at the end of the 1990s, that became the method to assess CACS in clinical practice, proving to be at least comparable, and, in many aspects, superior to electron-beam CT for that purpose.</p>
      <p>Thus, in this article, all technical considerations about CACS image acquisition refer to multidetector CT.</p>
      <p>Determining CACS is based on a non-contrasted acquisition of a series of 3-mm axial slices covering the entire heart extension. Images are acquired synchronously with the signal of the electrocardiogram (ECG). The protocol of synchronization with the ECG can be prospective or retrospective. The radiation dose used in the retrospective acquisition protocols is significantly higher; thus, prospective protocols are more commonly used. In practice, the effective radiation dose in a prospective acquisition is low, being usually under 1.5 mSv, and, on average, around 0.9 mSv to 1.1 mSv.</p>
      <p>Calcification is defined as a hyperattenuating lesion with signal intensity over 130 Hounsfield units (HU) and area <underline>&gt;</underline> 3 adjacent pixels (at least 1 mm<sup>2</sup>). It can be calculated based on the weighted sum of densities over 130 HU (Agatston score) or by use of methods determining calcium volume or mass. Although calcium volume or mass scores have better reproducibility, the large population data banks that describe the distribution of coronary calcification according to the patients' age, ethnicity and sex are based on the Agatston score, which is, thus, the most often used score in clinical practice (<xref ref-type="fig" rid="en_12f01-body2">Figure 1</xref>).</p>
      <p content-type="asset">
        <fig id="en_12f01-body2">
          <graphic xlink:href="1678-4170-abc-98-06-0559-00012-gf01-en.jpg"/></fig>
      </p>
      <p>
        <bold>One question still remains: How are the results of CACS classified and interpreted?</bold>
      </p>
      <p>The CACS values obtained can be classified by using either fixed cut-off points or cut-off points adjusted for the patients' age, sex, and, more recently, ethnicity. The more accepted limit values in the two classification types are shown in <xref ref-type="table" rid="t1-body2">table 1</xref>.</p>
      <table-wrap id="t1-body2">
        <graphic xlink:href="1678-4170-abc-98-06-0559-00012-gt01-en.jpg"/></table-wrap>
      <p>In the classification using fixed cut-off points, the patients are categorized according to pre-established limits. In the classification using adjusted cut-off points, the patients are categorized according to the percentiles of distribution of the CACS values of the general population (<xref ref-type="fig" rid="en_12f02-body2">Figure 2</xref>). It is worth noting, however, that both classification types provide valuable prognostic information and are present in the reports provided by diagnostic centers trained in performing cardiac imaging.</p>
      <p content-type="asset">
        <fig id="en_12f02-body2">
          <graphic xlink:href="1678-4170-abc-98-06-0559-00012-gf02-en.jpg"/></fig>
      </p>
      <p>Initially, CACS was used as a diagnostic tool aimed at identifying or excluding the presence of obstructive CAD in symptomatic patients. The initial studies have shown that CACS has an excellent negative predictive value (NPV) to exclude the presence of significant CAD (96% to 100%), but the positive predictive value (PPV) was, at most, moderate<sup>14</sup>. In contrast, more recent studies have shown that, particularly in younger patients or in a population with a high prevalence of significant CAD, in addition to the inadequate PPV, CACS shows a NPV insufficient to exclude the presence of significant obstructive disease.</p>
      <p>In fact, Gottlieb et al.<sup>15</sup> have shown that, in a population with a 56% prevalence of significant CAD, even 19% of the patients with CACS = 0 had at least one obstructive lesion <underline>&gt;</underline> 50% on invasive coronary angiography<sup>15</sup>. Considering the only moderate PPV and the conflicting data regarding the NPV, the current concept is that, in general, CACS should not be used as a tool to diagnose significant obstructive CAD in symptomatic patients. The actual value of CACS in clinical practice consists in its capacity to provide valuable prognostic information and to serve as an important tool for risk stratification of asymptomatic patients.</p>
      <p>
        <bold>Prognostic value</bold>
      </p>
      <p>An important concept to understand why CACS bears the potential to play a relevant role in cardiovascular risk stratification is that coronary artery calcification represents a marker of the presence of atherosclerotic plaques in coronary arteries. In the coronary arterial bed, calcification occurs almost exclusively in the context of atherosclerotic disease. In a certain individual, the amount of calcification in the coronary arteries has a good correlation with the total coronary atherosclerotic burden. However, not the entire atherosclerotic plaque is calcified. In fact, previous reports have shown that the calcified portion corresponds to only 20% of the total plaque volume, that is, the coronary artery calcification would represent only the "iceberg tip" of CAD, and the non-calcified portion would account for 80% of the total coronary atherosclerotic burden.</p>
      <p>It is worth noting that the presence or absence of calcium has not been significantly associated with the propensity to rupture of a certain plaque, and that the presence of calcification is a signal of neither "stability" nor "instability" of any plaque.</p>
      <p>Several population longitudinal studies involving a large number of patients have shown that CACS is significantly associated with the occurrence of major cardiovascular events (all-cause death, cardiac death, and non-fatal AMI) in the medium- and long-term follow-up. The higher the amount of calcium in the coronary arteries, the greater the chance of the patient having a cardiovascular event in the future.</p>
      <p>Even more important, a series of previous studies have shown that the capacity of CACS to predict the occurrence of cardiovascular events is additional to the risk stratification by use of the Framingham score and other methods, such as C-reactive protein measurement. In fact, a classical study<sup>16</sup> has shown that patients at intermediate risk according to the Framingham score and with CACS &gt; 300 have a rate of cardiovascular events of 2.8%/year (approximately equivalent to a 28% rate over ten years), which would place them in the high-risk group (&gt; 20% over ten years).</p>
      <p>A recent consensus published by the ACCF/AHA on the CACS use to assess global cardiovascular risk<sup>12</sup> has analyzed the combined data of six large studies that included 27,622 asymptomatic patients and has assessed the major predictors of a total of 395 cardiovascular events. Of the 11,815 patients with CACS = 0, the rate of events was very low, only 0.4% over the three to five subsequent years. When compared with patients with a CACS = 0, those with a CACS between 100 and 400 had a relative risk (RR) of 4.3 (95% confidence interval [95% CI]: 3.5 - 5.2; p &lt; 0.0001), those with a CACS between 400 and 1000 had a RR of 7.2 (95% CI: 5.2 - 9.9; p &lt; 0.0001), and those with a CACS &gt; 1000 had a RR of 10.8 (95% CI: 4.2 - 27.7; p &lt; 0.0001).</p>
      <p>Since the publication of that consensus, other prospective studies have confirmed those findings and have demonstrated that the association between CACS and prognosis is similar regardless of the patients' sex or ethnicity<sup>14,17</sup>. Even more important, all such studies have also confirmed that CACS can provide additional prognostic information as compared with the assessment by use of the traditional risk factors alone. On the ROC analysis, the area under the curve to predict the occurrence of cardiovascular events was significantly greater with CACS than with the Framingham or PROCAM risk scores. In the MESA study, considering only the traditional risk factors, the C statistics was 0.79 to predict major cardiovascular events, and 0.83 when the CACS information was associated with that of risk factors (p = 0.006)<sup>17</sup>.</p>
      <p>Previous studies have also shown that CACS provides additional prognostic information to the C-reactive protein assessment. In four studies based on multivariate models, CACS remained as an independent predictor of major cardiovascular events, while the C-reactive protein no longer was a significant predictor on multivariate analyses<sup>18-21</sup>. When compared with the carotid intima/media thickness (IMT) measurement, CACS proved to be a better predictor of subsequent events; the hazard ratio (HR) of the IMT was 1.7 (95% CI: 1.1 - 2.7; p = 0.07), while the HR of the CACS was 8.2 (95% CI: 4.5 - 15.1; p = 0.001)<sup>22</sup>.</p>
      <p>
        <bold>Potential to change clinical management</bold>
      </p>
      <p>In addition to its role as a risk stratification tool, another important aspect of CACS relates to its potential to change and help with the clinical management of patients suspected of having CAD. In an observational study, Kalia et al.<sup>23</sup> have shown that the use rate of lipid-lowering drugs in dyslipidemic patients increased from 44% to over 90% in those with severe calcification on CACS assessment<sup>23</sup>. Other preventive behavioral measures, such as the regular practice of physical exercises and the adoption of healthier diets, have also shown an improvement in the subgroup with higher CACS values. Moreover, in a prospective study following 1,640 patients up for a mean period of six years, the use rates of statins and aspirin were 3.5 and 3 times greater, respectively, in the subgroup with calcification plaques on the CACS<sup>24</sup>. That significant increase did not depend on other risk factors and demonstrated the CACS potential to change clinical management in a sample of the general population.</p>
      <p>According to the results of the JUPITER study<sup>25</sup>, a large number of asymptomatic patients with LDL levels considered normal have begun to have indication for statin treatment. In that study, the major criterion to indicate statin treatment was ultra-sensitive C-reactive protein test. However, recent data of the MESA study have shown that the subgroup of patients with indication for statin treatment according to the criteria of the JUPITER study, but who had no coronary calcification on CACS assessment, were at low risk for cardiovascular events. Considering that in the JUPITER study the reduction in the absolute risk of the entire population was low, the authors of the MESA study have concluded that CACS might play a relevant role in selecting those with the greater potential to benefit from the treatment, among all patients who met the criteria for receiving statins. In other words, not C-reactive protein alone, but its combination with CACS would be a better strategy to select patients with the greatest potential to benefit from the treatment with statins.</p>
      <p>
        <bold>Current recommendations</bold>
      </p>
      <p>In an expert consensus on the use of CACS for assessing the global cardiovascular risk published by the ACCF/AHA in 2007<sup>12</sup>, asymptomatic patients classified as at intermediate risk by the Framingham risk score were considered good candidates to the CACS assessment aiming at refining the stratification, and potentially changing clinical management. In that document, the authors have not classified the recommendation grade.</p>
      <p>More recently, in the 2010 ACCF/AHA guideline for assessment of cardiovascular risk in asymptomatic patients<sup>5</sup>, the CACS quantification for cardiovascular risk stratification in individuals classified as at intermediate risk by the Framingham risk score was considered a class IIa indication, with level of evidence B. It is worth noting that in that document, the only intervention considered as class I was the stratification using global risk scores based on the traditional risk factors, such as the Framingham risk score, and the clinical assessment regarding the presence of early CAD family history. Neither imaging nor laboratory diagnostic exams were classified as class I recommendation grade.</p>
      <p>For the purpose of comparison, in that document, echocardiography, exercise test, and myocardial perfusion scintigraphy were considered class IIb or III recommendation grade indications.</p>
      <p>Finally, in the ACCF/SCCT/ACR/AHA/ASE/ASNC/NASCI/SCAI/SCMR 2010 appropriate use criteria for cardiac CT report<sup>8</sup>, the use of CACS for stratifying the global cardiovascular risk of patients classified as at intermediate risk by the Framingham risk score was rated as a level 7 (A7) appropriate indication. That report used a scale ranging from 1 to 9 to designate appropriateness as follows: 1-3, inappropriate use; 4-6, uncertain; and 7-9, appropriate. In that document, the CACS use was also considered a level 7 (A7) appropriate indication in patients classified as at low risk by the Framingham risk score, but who had an early CAD family history.</p>
      <p>Regarding the Brazilian recommendations, the 2006 Brazilian Society of Cardiology guidelines on the use of cardiac CT<sup>7</sup> defined the use of CACS for stratifying the global cardiovascular risk of patients classified as at intermediate risk by the Framingham risk score as a class I indication. That same document defined as a class IIa indication the use of CACS in patients classified as at low risk by the Framingham risk score, but who had an early CAD family history.</p>
      <p>
        <bold>Coronary computed tomographic angiography</bold>
      </p>
      <p>
        <bold>The test</bold>
      </p>
      <p>Coronary computed tomographic angiography (CCTA) became possible with the advent of multidetector CT devices at the end of the 1990s. It began to be clinically used from the beginning of the following decade, after the introduction of 16-row detector CT devices. Since then, the technological development in that area has been vertiginous, and currently devices with 256 rows and even 320 rows of detectors are available, allowing the acquisition of all images necessary for coronary assessment at one single heartbeat.</p>
      <p>The CCTA is based on the acquisition of a series of axial slices with submillimetric thickness covering the entire cardiac extension. Similarly to CACS, the images are acquired synchronously with the ECG signal. The ECG synchronization protocol can be prospective sequential or retrospective helical. Considering the 64-row devices currently available, while the amount of radiation of one retrospective acquisition with dose modulation is around 9.0 mSv, the effective dose of a prospective acquisition is around 3.0 mSv<sup>26</sup>.</p>
      <p>For the purpose of comparison, the radiation dose of a conventional technetium or sestamibi myocardial perfusion scintigraphy is also around 9.0 mSv. The radiation dose of a thallium myocardial perfusion scintigraphy is around 18.0 mSv. It is worth noting that, in general, the medical community has made a great effort to progressively reduce the amount of radiation used in cardiologic tests, and that the current devices with <underline>&gt;</underline> 256 rows already allow performing coronary tomographic angiography with effective radiation doses lower than 1.0 mSv.</p>
      <p>
        <bold>Diagnostic value</bold>
      </p>
      <p>There are some systematic reviews assessing the diagnostic value of CCTA since the advent of 64-row devices in 2004<sup>27-30</sup>. In general, those studies have shown an improvement in the diagnostic accuracy of the method with the technology evolution from 4- and 16-row devices to current 64-row devices. Similarly, the number of coronary artery segments not analyzable has decreased with the technological development. Based on those conclusions, the following concept has been established: although the clinical application of the method has been possible from 16-row devices, state-of-the-art CCTA requires the use of devices with at least 64 rows, mainly due to its greater longitudinal coverage and better spatial and temporal resolution (<xref ref-type="fig" rid="en_12f03-body2">Figure 3</xref>).</p>
      <p content-type="asset">
        <fig id="en_12f03-body2">
          <graphic xlink:href="1678-4170-abc-98-06-0559-00012-gf03-en.jpg"/></fig>
      </p>
      <p>Currently there are more than 50 single-center studies<sup>29</sup> and three multicenter studies<sup>31-33</sup> assessing the accuracy of CCTA with 64-row devices for the assessment of stable symptomatic patients suspected of having significant CAD. In all cases, CCTA has been compared with the current reference method, invasive conventional coronary angiography. In general, those studies have very consistently demonstrated that CCTA has an excellent accuracy to detect or exclude the presence of significant CAD. In particular, they have shown a particularly high NPV, making the test especially useful to exclude the presence of significant obstructive lesions in that population.</p>
      <p>In the most recent systematic review assessing the single-center studies carried out until the end of 2007 using 64-row devices<sup>29</sup>, the mean sensitivity to identify the presence of significant CAD was 98% and the mean specificity was 88%. The mean prevalence of significant CAD in those studies was 61% and the PPV and NPV were 93% and 96%, respectively.</p>
      <p>In the multicenter CORE 64 study<sup>32</sup>, assessing 291 patients with clinical indication for invasive coronary angiography, the prevalence of significant CAD was 56%. In that study, the sensitivity and specificity of CCTA, in an analysis per patient, were 85% and 90%, respectively. The area under the ROC curve was 0.93. The PPV was 91% and the NPV was 83%.</p>
      <p>In the multicenter ACCURACY trial<sup>31</sup>, assessing 245 symptomatic patients, the prevalence of significant CAD was 25% for stenoses <underline>&gt;</underline> 50% and only 14% for stenoses <underline>&gt;</underline> 70%. In that study, sensitivity was 94% or 95%, depending on the threshold chosen to define the presence of significant CAD. Specificity was 82%. The NPV was 99% for both the 50% and 70% thresholds. The PPV was only 48% for the 70% threshold, and 64% for the 50% threshold.</p>
      <p>Finally, a multicenter study performed at three Dutch university-affiliated hospitals has assessed 360 patients with indication for invasive coronary angiography<sup>33</sup>. The prevalence of significant CAD was 68%. The sensitivity and specificity of CCTA, in an analysis per patient, were 100% and 64%, respectively. The PPV was 86% and the NPV was 97%.</p>
      <p>
        <bold>Prognostic value</bold>
      </p>
      <p>In recent years, a large number of studies have assessed the role played by magnetic resonance and CT not only for the diagnostic evaluation<sup>13,31-39</sup>, but also for the prognostic evaluation<sup>40-47</sup> of patients with cardiovascular diseases. Regarding cardiac CT, a recent series of studies have shown that, not only the CACS assessment, but also the assessment of coronary anatomy by use of CCTA provide important prognostic information in patients suspected of having significant CAD<sup>42,44,45,47-49</sup>. Using a 16-row detector CT device, Min et al.<sup>44</sup> have studied 1,127 patients and assessed the relationship between all-cause mortality and the results of CCTA. After a mean 15-month follow-up, the authors have shown that the CAD severity on CCTA was an important predictive factor of total mortality, providing additional prognostic information to the traditional risk factors.</p>
      <p>In another important study, Ostrom et al.<sup>45</sup> have assessed 2,538 patients by use of CCTA with an electron-beam CT device<sup>45</sup>. After a mean 78-month follow-up, the authors have shown that CCTA has an incremental prognostic value to not only traditional risk factors, but also to the CACS assessment. Later, van Werkhoven et al.<sup>49</sup> have assessed 541 patients undergoing both CCTA and myocardial perfusion imaging. After a mean 22-month follow-up assessing the combined endpoints of cardiac death, nonfatal infarction and hospitalization due to unstable angina, the authors have demonstrated that both the anatomical assessment through tomographic angiography and functional evaluation by use of myocardial perfusion imaging provide important prognostic information, the former having an incremental prognostic value over the latter.</p>
      <p>In a recent study, Azevedo et al.<sup>48</sup> have assessed 529 patients suspected of having obstructive CAD, who had undergone ischemia tests with inconclusive results. Those authors have shown that 70% of those patients had no significant obstructive lesion. In fact, approximately 40% had completely normal coronary arteries, with CACS = 0. Moreover, after a mean 30-month follow-up, those authors showed that both CACS and CCTA provided important prognostic information on that population.</p>
      <p>In addition, recently, Hadamitzky et al.<sup>42</sup>, studying 2,223 patients with suspected CAD for a mean period of 28 months, have confirmed the findings of previous studies by demonstrating that CCTA provides important prognostic information, which is incremental to clinical risk scores and CACS<sup>42</sup>. In the ROC analysis, the area under the curve to predict the occurrence of cardiovascular events was 0.79 for the clinical score alone, 0.84 for the clinical score plus CACS, and 0.89 for the clinical score plus CACS plus CCTA (p &lt; 0.001).</p>
      <p>
        <bold>Characterization of the atherosclerotic plaque</bold>
      </p>
      <p>An important characteristic of CCTA, which distinguishes it from invasive coronary angiography, is its ability to provide the assessment of coronary arterial walls in addition to the visualization of the vessel's lumen. Thus, it allows not only the identification of the lesions causing luminal obstruction, but also the characterization of atherosclerotic plaques, either obstructive or non-obstructive. In fact, several previous studies have shown the good correlation of plaque volume measured on CCTA with the measures obtained with the current gold standard method, intravascular ultrasound<sup>50</sup>.</p>
      <p>Even more important, recent reports have suggested that the characterization of atherosclerotic plaques on CCTA has the potential to help in identifying the most vulnerable patients to an acute coronary event. Motoyama et al.<sup>51</sup> have assessed 1,059 patients regarding the presence of two parameters measured by use of CCTA: the grade of positive remodeling and the presence of low-attenuation areas in the plaque, suggesting lipid content<sup>51</sup>. The mean follow-up time was 27 months. The rate of cardiovascular events in 45 patients with those two parameters was 22.2%. In contrast, that rate in patients with only one of those parameters was 3.7%, and in those with none of those parameters was 0.4%.</p>
      <p>However, it is worth noting that the use of CCTA aiming at characterizing atherosclerotic plaques and identifying those with signs suggestive of vulnerability does not yet represent a clinically established indication, being currently under experimental development.</p>
      <p>
        <bold>Conclusion</bold>
      </p>
      <p>Currently, the two major uses of CT to assess CAD are as follows: CACS measurement and CCTA itself. The CACS provides important prognostic information that is incremental to the clinical scores based on traditional risk factors and other diagnostic modalities, such as C-reactive protein measurement. In addition, CACS has the potential to change and help the patients' clinical management. Thus, performing CACS is indicated for the global cardiovascular risk stratification of asymptomatic patients rated as at intermediate risk according to the Framingham risk score.</p>
      <p>On the other hand, CCTA provides a detailed assessment of the anatomy of the coronary arteries, allowing visualizing not only the lumen, but also the coronary arterial walls. Compared to conventional invasive coronary angiography, CCTA has excellent accuracy to identify and mainly exclude the presence of significant obstructive lesions. In addition, it proved to be able to provide incremental prognostic information to the traditional risk factors and CACS. However, although CCTA represents a very useful diagnostic tool, being indicated for the diagnostic assessment of symptomatic patients suspected of having CAD, it is currently not indicated when the only objective is the global cardiovascular risk stratification of asymptomatic patients.</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 study is not associated with any post-graduation program.</p>
      <p>
        <bold>References</bold>
      </p>
    </body>
  </sub-article>
</article>
