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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">kPq5nqVBRnmxsLfvzC5nHNs</article-id>
      <article-id pub-id-type="other">00008</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v2">S0066-782X2006001500008</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v1">S0066-782X(06)08700208</article-id>
      <article-id pub-id-type="doi">10.1590/S0066-782X2006001500008</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Artigos Originais</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Estenose a&#243;rtica e doen&#231;a coronariana: an&#225;lise dos fatores de risco</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Rangel</surname>
            <given-names>Claudio Magalh&#227;es</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Grinberg</surname>
            <given-names>Max</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Maranh&#227;o</surname>
            <given-names>Raul Cavalcante</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Ventura</surname>
            <given-names>Laura In&#234;s</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
      </contrib-group>
      <aff id="aff01">
        <addr-line>
          <named-content content-type="city">S&#227;o Paulo</named-content>
          <named-content content-type="state">S&#227;o Paulo</named-content>
        </addr-line>
        <institution content-type="orgname">Universidade de S&#227;o Paulo</institution>
        <institution content-type="orgdiv1">Hospital das Cl&#237;nicas </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>08</month>
        <year>2006</year>
      </pub-date>
      <volume>87</volume>
      <issue>2</issue>
      <fpage>115</fpage>
      <lpage>120</lpage>
      <history>
        <date date-type="accepted">
          <day>17</day>
          <month>03</month>
          <year>2006</year>
        </date>
        <date date-type="received">
          <day>13</day>
          <month>10</month>
          <year>2004</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>OBJETIVO: Analisar aspectos cl&#237;nico-laboratoriais da presen&#231;a de doen&#231;a coronariana em pacientes portadores de estenose a&#243;rtica e analisar a influ&#234;ncia de fatores de risco para o desenvolvimento de coronariopatia obstrutiva. M&#201;TODOS: Estudamos 65 pacientes portadores de estenose a&#243;rtica severa com indica&#231;&#227;o de cirurgia, com idade entre 51 a 85 anos, entre os quais havia 40 mulheres. Da realiza&#231;&#227;o da cinecoronariografia resultaram dois grupos: 26(40%) com coronariopatia obstrutiva e 39(60%) sem les&#245;es em art&#233;rias coron&#225;rias. Foram analisados os antecedentes pessoais para doen&#231;a coronariana (h&#225;bito de fumar, dislipidemia, diabetes mellitus, hipertens&#227;o arterial, antecedentes familiares, sedentarismo e alcoolismo), eletrocardiograma, ecocardiograma com Doppler e exames laboratoriais (glicemia, colesterol total e fra&#231;&#245;es, triglic&#233;rides, Apo A1 e B, fibrinog&#234;nio, lipoproteina(a) e taxa fracional de remo&#231;&#227;o de triglic&#233;rides e colesterol nos dois grupos. RESULTADOS: Na an&#225;lise da idade, o grupo com coronariopatia obstrutiva apresentou faixa et&#225;ria mais elevada com signific&#226;ncia estat&#237;stica (p&lt;0,0001). A identifica&#231;&#227;o de sinais de isquemia em parede anterior no eletrocardiograma apresentou rela&#231;&#227;o significante com obstru&#231;&#227;o em art&#233;ria interventricular anterior (p&lt;0,002). A an&#225;lise univariada mostrou diferen&#231;a significante entre os grupos em rela&#231;&#227;o &#224;s m&#233;dias das vari&#225;veis gradiente a&#243;rtico (p= 0,041), HDL (p=0,042) e fibrinog&#234;nio (p=0,047). O grupo com doen&#231;a coronariana apresentou m&#233;dia do gradiente e HDL menor que os sem coronariopatia obstrutiva. Na vari&#225;vel fibrinog&#234;nio, o grupo sem doen&#231;a coronariana apresentou m&#233;dia com n&#237;veis menores comparados aos dos portadores de coronariopatia. A an&#225;lise multivariada pelo m&#233;todo da regress&#227;o log&#237;stica mostrou como vari&#225;vel independente para coronariopatia os n&#237;veis de fibrinog&#234;nio ( p&lt;0,039). CONCLUS&#195;O: O fibrinog&#234;nio foi fator de risco independente para a associa&#231;&#227;o de coronariopatia obstrutiva com estenose a&#243;rtica.</p>
      </abstract>
      <kwd-group xml:lang="pt" kwd-group-type="author-generated">
        <kwd>Estenose da valva a&#243;rtica</kwd>
        <kwd>coronariopatia</kwd>
        <kwd>fatores de risco</kwd>
      </kwd-group>
      <pub-date publication-format="electronic" date-type="pub">
        <day>28</day>
        <month>09</month>
        <year>2006</year>
      </pub-date>
    </article-meta>
  </front>
  <body>
    <p>
      <bold>ARTIGO ORIGINAL</bold>
    </p>
    <p>Estenose a&#243;rtica e doen&#231;a coronariana. An&#225;lise dos fatores de risco</p>
    <p>
      <bold>Claudio Magalh&#227;es Rangel; Max Grinberg; Raul Cavalcante Maranh&#227;o; Laura In&#234;s Ventura</bold>
    </p>
    <p>Instituto do Cora&#231;&#227;o do Hospital das Cl&#237;nicas &#150; FMUSP - S&#227;o Paulo, SP</p>
    <p>
      <xref ref-type="corresp" rid="end">Correspond&#234;ncia</xref>
    </p>
    <p>
      <bold>RESUMO</bold>
    </p>
    <p><bold>OBJETIVO: </bold>Analisar aspectos cl&#237;nico-laboratoriais da presen&#231;a de doen&#231;a coronariana em pacientes portadores de estenose a&#243;rtica e analisar a influ&#234;ncia de fatores de risco para o desenvolvimento de coronariopatia obstrutiva. </p>
    <p><bold>M&#201;TODOS: </bold>Estudamos 65 pacientes portadores de estenose a&#243;rtica severa com indica&#231;&#227;o de cirurgia, com idade entre 51 a 85 anos, entre os quais havia 40 mulheres. Da realiza&#231;&#227;o da cinecoronariografia resultaram dois grupos: 26(40%) com coronariopatia obstrutiva e 39(60%) sem les&#245;es em art&#233;rias coron&#225;rias. Foram analisados os antecedentes pessoais para doen&#231;a coronariana (h&#225;bito de fumar, dislipidemia, diabetes mellitus, hipertens&#227;o arterial, antecedentes familiares, sedentarismo e alcoolismo), eletrocardiograma, ecocardiograma com Doppler e exames laboratoriais (glicemia, colesterol total e fra&#231;&#245;es, triglic&#233;rides, Apo A1 e B, fibrinog&#234;nio, lipoproteina(a) e taxa fracional de remo&#231;&#227;o de triglic&#233;rides e colesterol nos dois grupos. </p>
    <p><bold>RESULTADOS: </bold>Na an&#225;lise da idade, o grupo com coronariopatia obstrutiva apresentou faixa et&#225;ria mais elevada com signific&#226;ncia estat&#237;stica (p&lt;0,0001). A identifica&#231;&#227;o de sinais de isquemia em parede anterior no eletrocardiograma apresentou rela&#231;&#227;o significante com obstru&#231;&#227;o em art&#233;ria interventricular anterior (p&lt;0,002). A an&#225;lise univariada mostrou diferen&#231;a significante entre os grupos em rela&#231;&#227;o &#224;s m&#233;dias das vari&#225;veis gradiente a&#243;rtico (p= 0,041), HDL (p=0,042) e fibrinog&#234;nio (p=0,047). O grupo com doen&#231;a coronariana apresentou m&#233;dia do gradiente e HDL menor que os sem coronariopatia obstrutiva. Na vari&#225;vel fibrinog&#234;nio, o grupo sem doen&#231;a coronariana apresentou m&#233;dia com n&#237;veis menores comparados aos dos portadores de coronariopatia. A an&#225;lise multivariada pelo m&#233;todo da regress&#227;o log&#237;stica mostrou como vari&#225;vel independente para coronariopatia os n&#237;veis de fibrinog&#234;nio ( p&lt;0,039). </p>
    <p><bold>CONCLUS&#195;O: </bold>O fibrinog&#234;nio foi fator de risco independente para a associa&#231;&#227;o de coronariopatia obstrutiva com estenose a&#243;rtica.</p>
    <p><bold>Palavras-chave: </bold>Estenose da valva a&#243;rtica, coronariopatia, fatores de risco.</p>
    <p>A estenose a&#243;rtica no adulto caracteriza-se por altera&#231;&#245;es degenerativas das c&#250;spides valvares que dificulta o esvaziamento adequado do ventr&#237;culo esquerdo, favorecendo o desenvolvimento de hipertrofia muscular devido &#224; sobrecarga cr&#244;nica e progressiva de press&#227;o do ventr&#237;culo esquerdo. As principais causas de estenose a&#243;rtica s&#227;o a cong&#234;nita, reum&#225;tica e a degenerativa ou senil.</p>
    <p>Quando analisamos a express&#227;o "fator de risco"<sup>1</sup>, descrevemos as caracter&#237;sticas que podem ser encontradas em indiv&#237;duos saud&#225;veis, que se associam de forma independente com a manifesta&#231;&#227;o de uma determinada doen&#231;a. Nesse sentido, um fator de risco pode ser definido como qualquer tra&#231;o ou caracter&#237;stica mensur&#225;vel de um indiv&#237;duo que possa lev&#225;-lo a uma maior probabilidade de vir a manifestar uma determinada doen&#231;a<sup>2</sup>.</p>
    <p>Uma metan&#225;lise de 33 estudos mostrou 37% de preval&#234;ncia de doen&#231;a coronariana em pacientes com estenose a&#243;rtica calcificada<sup>3</sup>. Ainda existem d&#250;vidas em rela&#231;&#227;o aos fatores de risco da doen&#231;a arterial coronariana no paciente com estenose a&#243;rtica. Na an&#225;lise dos fatores de risco da doen&#231;a coronariana, n&#227;o h&#225; condi&#231;&#245;es de afirmar qual &#233; o grau de participa&#231;&#227;o desses fatores no desenvolvimento da coronariopatia associada &#224; estenose a&#243;rtica. Seria de extrema import&#226;ncia cl&#237;nica, na an&#225;lise dos fatores de risco do paciente com estenose a&#243;rtica, conhecer qual a probabilidade de esse paciente apresentar doen&#231;a coronariana associada. As respostas a essas perguntas poderiam facilitar a identifica&#231;&#227;o da probabilidade de o paciente com estenose a&#243;rtica ser portador de coronariopatia associada. Poder&#237;amos determinar a rela&#231;&#227;o de cada fator de risco, isolado ou associado, na participa&#231;&#227;o do desenvolvimento da doen&#231;a coronariana no paciente com estenose a&#243;rtica e diminuir a morbimortalidade dessa associa&#231;&#227;o.</p>
    <p>
      <bold>M&#201;TODOS</bold>
    </p>
    <p>Participaram da pesquisa 65 pacientes dos quais 40 (61,5%) eram do sexo feminino e 25 (38,5%) do masculino. Os pacientes foram inclusos no protocolo conforme os seguintes crit&#233;rios de inclus&#227;o: presen&#231;a de estenose a&#243;rtica severa, aus&#234;ncia de outra valvopatia, idade &gt; 50 anos, sem cirurgia card&#237;aca pr&#233;via e aus&#234;ncia de patologia renal , hep&#225;tica, hematol&#243;gica ou neopl&#225;sica clinicamente significantes.</p>
    <p>Nos pacientes selecionados para o protocolo foi preenchida uma ficha cl&#237;nica que inclu&#237;a idade, sexo, &#237;ndice de massa corp&#243;rea, fatores de risco para doen&#231;a coronariana, dados de anamnese, eletrocardiograma, ecocardiograma com Doppler. No final dessa entrevista era marcado o dia dos exames de laborat&#243;rio e do cateterismo card&#237;aco.</p>
    <p>Na avalia&#231;&#227;o do &#237;ndice de massa foram usadas as medidas antropom&#233;tricas de peso e altura para posterior c&#225;lculo do &#237;ndice de massa corp&#243;rea (IMC) por meio da f&#243;rmula de IMC = peso(kg)/altura2(m<sup>2</sup>)<sup>4</sup>.</p>
    <p>Os fatores de risco selecionados foram: tabagismo (h&#225;bito de fumar mais de cinco cigarros por dia h&#225; pelo menos seis meses<sup>5</sup>), HDL-colesterol abaixo de 35 mg/dl, LDL-colesterol acima de 130 mg/dl<sup>6</sup>, diabetes mellitus (n&#237;veis de glicose acima de 140mg/dl ap&#243;s jejum noturno de 12 horas<sup>7</sup>), hipertens&#227;o arterial sist&#234;mica (pacientes com press&#227;o arterial sist&#243;lica maior que 150 mmHg e diast&#243;lica maior que 90 mmHg<sup>8</sup>), antecedentes familiares (pais ou irm&#227;os com hist&#243;ria de doen&#231;a coronariana ,com menos de 55 anos para os homens e menos de 65 anos para as mulheres<sup>2</sup>), sedentarismo (pacientes que referiram atividades como caminhar menos de 30 minutos por semana ou pr&#225;tica de esportes espor&#225;dicos<sup>2</sup>), alcoolismo (homens com ingesta de mais de 4 doses por dia ou mais que 20 doses por semana e mulheres com ingesta de mais de 3 doses por dia ou mais do que 12 doses por semana<sup>2</sup>).</p>
    <p>Os dados de anamnese foram definidos pela classe funcional pela classifica&#231;&#227;o da <italic>New York Heart Association</italic><sup>9</sup>, angina pela classifica&#231;&#227;o da <italic>Canadian Cardiovascular Society</italic><sup>10</sup>, s&#237;ncope e sintomas e sinais compat&#237;veis com insufici&#234;ncia card&#237;aca congestiva.</p>
    <p>Eletrocardiograma foi realizado em todos os pacientes nas 12 deriva&#231;&#245;es, utilizando-se aparelho <italic>Hewlett Packard</italic>, modelo 1700, de acordo com os crit&#233;rios convencionais. Como existem altera&#231;&#245;es eletrocardiogr&#225;ficas cl&#225;ssicas da estenose a&#243;rtica, analisaremos a associa&#231;&#227;o da presen&#231;a de isquemia da parede anterior com les&#227;o significativa da art&#233;ria descendente anterior. N&#227;o analisaremos a rela&#231;&#227;o causal com outras coron&#225;rias acometidas, por se confundirem com as altera&#231;&#245;es eletrocardiogr&#225;ficas cl&#225;ssicas presentes na estenose a&#243;rtica severa.</p>
    <p>O ecocardiograma com Doppler foi realizado em todos os pacientes, utilizando-se aparelho ATL modelo HDI 3000. Foi analisado o gradiente valvar a&#243;rtico m&#225;ximo aplicando-se a equa&#231;&#227;o modificada de Bernoulli<sup>11</sup>, e a fra&#231;&#227;o de eje&#231;&#227;o (FE) do ventr&#237;culo esquerdo pelo m&#233;todo do Cubo<sup>12,13</sup>.</p>
    <p>Os exames de sangue foram colhidos pela manh&#227; ap&#243;s per&#237;odo de 12 horas de jejum. As dosagens de glicemia, triglic&#233;rides, colesterol total e fra&#231;&#245;es, fibrinog&#234;nio, apoA1, apoB e Lp(a) foram realizadas pelo Laborat&#243;rio Cl&#237;nico do Instituto do Cora&#231;&#227;o. Foi tamb&#233;m inclusa neste estudo a realiza&#231;&#227;o da cin&#233;tica de remo&#231;&#227;o plasm&#225;tica de quilomicra artificiais, exame feito pelo Laborat&#243;rio de L&#237;pides do Instituto do Cora&#231;&#227;o.</p>
    <p>O cateterismo card&#237;aco foi realizado em todos os pacientes inclusos no estudo como um exame pr&#233;-operat&#243;rio, para ser analisada a anatomia coronariana e avaliada a necessidade de revasculariza&#231;&#227;o mioc&#225;rdica associada &#224; troca de v&#225;lvula a&#243;rtica. O exame foi realizado pela t&#233;cnica de Sones e Shirey<sup>14</sup>. Foram considerados coronarianos quando apresentavam pelo menos uma art&#233;ria subepic&#225;rdica com processo ateroscler&#243;tico com mais de 50% de redu&#231;&#227;o do l&#250;men vascular, quando comparado com o segmento normal mais pr&#243;ximo. </p>
    <p>As vari&#225;veis classificat&#243;rias ser&#227;o apresentadas descriti&#173;vamente em tabelas com freq&#252;&#234;ncias absolutas (n) e relativas (%). As associa&#231;&#245;es entre essas vari&#225;veis e a presen&#231;a de doen&#231;a coronariana ser&#227;o comparadas com o teste qui-quadrado, teste da raz&#227;o de verossimilhan&#231;a ou teste exato de Fisher<sup>15</sup>. Para a an&#225;lise da incid&#234;ncia de doen&#231;a coronariana por faixa et&#225;ria, foi utilizado o teste da raz&#227;o de verossimilhan&#231;a<sup>15</sup>.</p>
    <p>As vari&#225;veis cont&#237;nuas est&#227;o apresentadas descritiva&#173;mente em tabelas com m&#233;dias e desvio-padr&#227;o. As m&#233;dias dessas vari&#225;veis em rela&#231;&#227;o &#224; presen&#231;a de doen&#231;a coronariana foram comparadas com o teste <italic>t</italic> de Student<sup>16</sup>. As vari&#225;veis gradiente, glicose, triglic&#233;rides, Lp(a) e TRF (CE) foram submetidas &#224; transforma&#231;&#227;o logar&#237;tmica para a an&#225;lise dos par&#226;metros.</p>
    <p>As vari&#225;veis que apresentaram signific&#226;ncia estat&#237;stica, na an&#225;lise univariada, foram utilizadas para ajuste de um modelo de regress&#227;o log&#237;stica m&#250;ltipla com procedimento de sele&#231;&#227;o de vari&#225;veis <italic>stepwise</italic><sup>16</sup>.</p>
    <p>Os valores de p &lt; 0,05 foram considerados signifi&#173;cantes.</p>
    <p>
      <bold>RESULTADOS</bold>
    </p>
    <p>Nos 65 pacientes que participaram do estudo, a idade variou entre 51 e 85 anos (m&#233;dia 68), dos quais 40 (61,5%) eram mulheres. Da realiza&#231;&#227;o da cinecoronariografia resultaram 26 (40%) pacientes com coronariopatia obstrutiva e 39 (60%) sem doen&#231;a coron&#225;ria obstrutiva. </p>
    <p>Observamos maior propor&#231;&#227;o de incid&#234;ncia de doen&#231;a coronariana em faixas et&#225;rias mais elevadas. Houve diferen&#231;a (p&lt;0,0001) entre faixas et&#225;rias, ou seja, a faixa et&#225;ria de 71-80 anos apresentou maior propor&#231;&#227;o de pacientes com doen&#231;a em rela&#231;&#227;o &#224;s outras faixas.</p>
    <p>Houve associa&#231;&#227;o entre isquemia anterior ao eletrocar&#173;diograma e les&#227;o da art&#233;ria interventricular anterior. Dos 17 pacientes que apresentavam les&#227;o nessa art&#233;ria, 11 mostraram isquemia anterior ao eletrocardiograma (64,71%) com p&lt;0,002 (teste de Fisher).</p>
    <p>N&#227;o houve associa&#231;&#227;o significante entre os grupos com e sem doen&#231;a coronariana em rela&#231;&#227;o ao sexo, n&#250;mero de fatores de risco, antecedente familiar, HAS, DM, dislipidemia, tabagismo, sedentarismo e alcoolismo. N&#227;o se observou associa&#231;&#227;o significativa entre os grupos com e sem doen&#231;a coronariana para classe funcional, angina, s&#237;ncope e insufici&#234;ncia card&#237;aca.</p>
    <p>Observamos diferen&#231;a significativa entre os grupos em rela&#231;&#227;o &#224;s m&#233;dias das vari&#225;veis gradiente m&#225;ximo (p=0,041), HDL colesterol (p=0,042) e fibrinog&#234;nio (p=0,047). Os pacientes com doen&#231;a coronariana apresentaram m&#233;dia de gradiente e HDL menor do que a dos sem doen&#231;a coronariana. Na vari&#225;vel fibrinog&#234;nio, os pacientes sem doen&#231;a coronariana apresentavam uma m&#233;dia com n&#237;veis menores comparados com os dos portadores de coronariopatia (<xref ref-type="table" rid="tab01">tab. 1</xref>).</p>
    <table-wrap id="tab01">
      <graphic xlink:href="1678-4170-abc-87-02-0115-00008-gt01.jpg"/></table-wrap>
    <p>A influ&#234;ncia dos par&#226;metros analisados na presen&#231;a de doen&#231;a coronariana est&#225; descrito na <xref ref-type="table" rid="tab02">tabela 2</xref>. Observa-se que apenas o fibrinog&#234;nio exerceu influ&#234;ncia significante (p=0,039) para a presen&#231;a de doen&#231;a coronariana.</p>
    <table-wrap id="tab02">
      <graphic xlink:href="1678-4170-abc-87-02-0115-00008-gt02.jpg"/></table-wrap>
    <p>No modelo de regress&#227;o log&#237;stica para a presen&#231;a de doen&#231;a coronariana foram consideradas as vari&#225;veis explanat&#243;rias: gradiente, HDL e fibrinog&#234;nio. Essas vari&#225;veis apresentam signific&#226;ncia estat&#237;stica na an&#225;lise univariada. Ap&#243;s a sele&#231;&#227;o de vari&#225;veis pelo m&#233;todo <italic>stepwise</italic>, a vari&#225;vel fibrinog&#234;nio mostrou signific&#226;ncia. Na <xref ref-type="table" rid="tab02">tabela 2</xref> pode-se observar que o par&#226;metro estimado para o fibrinog&#234;nio &#233; positivo, indicando correla&#231;&#227;o positiva em rela&#231;&#227;o &#224; probabilidade de doen&#231;a coronariana (quanto maior o valor do fibrinog&#234;nio, maior a probabilidade de doen&#231;a coronariana). </p>
    <p>No <xref ref-type="fig" rid="grf01">gr&#225;fico 1</xref>, observa-se a distribui&#231;&#227;o de valores de sensibilidade e especificidade para diferentes probabilidades da doen&#231;a coronariana. O ponto de valor m&#225;ximo de ambos os &#237;ndices &#233; no valor de probabilidade 0,42. </p>
    <fig id="grf01">
      <graphic xlink:href="1678-4170-abc-87-02-0115-00008-gf01.jpg"/></fig>
    <p>A probabilidade de 0,42 corresponde a um valor de fibrinog&#234;nio de 370, ou seja, se os pacientes com valores acima de 370 forem classificados doentes coronarianos e os inferiores como n&#227;o doentes , obteremos sensibilidade de 57,7% e especificidade de 63,2% (<xref ref-type="fig" rid="grf01">gr&#225;ficos 1</xref> e <xref ref-type="fig" rid="grf02">2</xref>).</p>
    <fig id="grf02">
      <graphic xlink:href="1678-4170-abc-87-02-0115-00008-gf02.jpg"/></fig>
    <p>
      <bold>DISCUSS&#195;O</bold>
    </p>
    <p>A incid&#234;ncia de doen&#231;a coronariana em pacientes submetidos &#224; troca de valva a&#243;rtica &#233; estimada entre 7% e 66%<sup>17,18</sup>. Uma metan&#225;lise com 33 estudos mostrou 37% de preval&#234;ncia de doen&#231;a coronariana em pacientes com estenose a&#243;rtica calcificada<sup>3</sup>. Em nossa s&#233;rie, a preval&#234;ncia de 40% de doen&#231;a coronariana mostrou-se na m&#233;dia da faixa referida, como tamb&#233;m se verificou nos estudos bem conduzidos por Lund e cols.<sup>19</sup>, Mautner e cols.<sup>20</sup> e Paquay e cols.<sup>21</sup>.</p>
    <p>A m&#233;dia de 70 anos foi semelhante &#224; de outros autores como Vekshtein<sup>22</sup> e Bessone <sup>23</sup>. Em nossa s&#233;rie, a m&#233;dia da idade n&#227;o apresentou diferen&#231;a estat&#237;stica entre os dois grupos, apesar de os pacientes com coronariopatia apresentarem faixa et&#225;ria mais elevada. Verifica-se uma certa correla&#231;&#227;o entre idade e taxa de coronariopatia, em que a faixa et&#225;ria maior tem maior probabilidade de doen&#231;a coronariana associada a estenose a&#243;rtica<sup>22,23</sup>. Nossa m&#233;dia de idade mais elevada est&#225; de acordo com a encontrada na maioria da literatura.</p>
    <p>A presen&#231;a de doen&#231;a coronariana em pacientes com estenose a&#243;rtica tem sido motivo de muitos estudos, e alguns autores t&#234;m sugerido a correla&#231;&#227;o entre fatores de risco e presen&#231;a de coronariopatia no paciente valvar a&#243;rtico<sup>18,24-26</sup>. Tem sido pouco valorizada a participa&#231;&#227;o dos fatores de risco para doen&#231;a coronariana como preditivo da presen&#231;a de coronariopatia no portador de estenose a&#243;rtica<sup>18,24,26,27</sup>. Em alguns trabalhos, a aus&#234;ncia de fatores de risco e angina foram suficientes para excluir doen&#231;a coronariana com a valvopatia<sup>26</sup>. De modo contr&#225;rio, Acar e cols.<sup>28</sup> e Pluta e cols.<sup>18</sup> acharam incid&#234;ncia de fatores de risco alta em pacientes com coronariopatia associada a estenose a&#243;rtica, enquanto Carstens e cols.<sup>29</sup> e Exadactylos e cols.<sup>30</sup> n&#227;o encontraram correla&#231;&#227;o entre a presen&#231;a de fatores de risco e a incid&#234;ncia de doen&#231;a coronariana associada com estenose a&#243;rtica. Em nossa casu&#237;stica, o maior n&#250;mero de fatores de risco n&#227;o aumentou a incid&#234;ncia de coronariopatia, o que est&#225; concordante com os trabalhos de Carstens<sup>29</sup> e Exadactylos<sup>30</sup>.</p>
    <p>Alguns autores<sup>24,31,32</sup> observaram que o gradiente a&#243;rtico tende a ser menor em pacientes com angina do que aqueles sem, particularmente quando a angina &#233; severa. Essa observa&#231;&#227;o pode ser causada pela grande preval&#234;ncia de doen&#231;a coronariana associada &#224; estenose a&#243;rtica moderada. Berndt e cols.<sup>33</sup> demonstraram que o gradiente a&#243;rtico foi menor nos pacientes que apresentavam doen&#231;a coronariana, o que tamb&#233;m foi um resultado observado em nossa casu&#237;stica. V&#225;rios outros autores<sup>18,24,28,31,32</sup> tiveram esse mesmo resultado, levantando a hip&#243;tese de que a isquemia mioc&#225;rdica ou infarto poderia potencialmente diminuir o gradiente pela valva a&#243;rtica.</p>
    <p>V&#225;rios estudos da literatura<sup>34-38</sup> observaram que n&#237;veis diminu&#237;dos de HDL-c aumentam o risco de doen&#231;a coronariana e, principalmente, se os valores de triglic&#233;dides est&#227;o tamb&#233;m elevados. A nossa casu&#237;stica apresentou n&#237;veis de HDL-c maiores nos pacientes com estenose a&#243;rtica sem doen&#231;a coronariana, o que refor&#231;a o conceito de fator protetor para coronariopatia. Esse resultado da nossa casu&#237;stica &#233; um dado importante para que, com outros fatores, possamos determinar frente a um paciente a probabilidade de apresentar doen&#231;a coronariana associada &#224; estenose a&#243;rtica.</p>
    <p>O n&#237;vel de fibrinog&#234;nio plasm&#225;tico tem sido mostrado como preditor de doen&#231;a coronariana em v&#225;rios estudos prospectivos<sup>39,40</sup>. Em sete estudos<sup>41,42</sup> prospectivos observou-se um aumento da incid&#234;ncia de doen&#231;a coronariana quando os n&#237;veis de fibrinog&#234;nio est&#227;o elevados. A participa&#231;&#227;o do fibrinog&#234;nio como fator de risco na coronariopatia do paciente valvulopata n&#227;o foi relatada pela literatura at&#233; o momento. Em nosso trabalho, estudamos essa correla&#231;&#227;o que se mostrou estatisticamente significativa na an&#225;lise univariada (<xref ref-type="table" rid="tab01">tab. 1</xref>) e no modelo de regress&#227;o log&#237;stica (<xref ref-type="table" rid="tab02">tab. 2</xref>). &#201; um fator importante para se analisar a probabilidade de um paciente com estenose a&#243;rtica ele apresentar coronariopatia associada, pois com o aumento progressivo dos n&#237;veis de fibrinog&#234;nio aumenta a probabilidade desta associa&#231;&#227;o (<xref ref-type="fig" rid="grf02">gr&#225;fico 2</xref>).</p>
    <p>Em conclus&#227;o, a verifica&#231;&#227;o do n&#237;vel de fibrinog&#234;nio na pr&#225;tica cl&#237;nica pode ser indicativo de aumento da preval&#234;ncia de coronariopatia obstrutiva em pacientes com estenose a&#243;rtica. Esse resultado foi observado em nosso trabalho, em que o n&#237;vel do fibrinog&#234;nio foi fator de risco independente para a associa&#231;&#227;o de coronariopatia obstrutiva com estenose a&#243;rtica; n&#237;veis mais elevados aumentaram a probabilidade dessa associa&#231;&#227;o. Este dado, com a an&#225;lise do gradiente a&#243;rtico, faixa et&#225;ria, eletrocardiograma e HDL-c, pode ser de extrema import&#226;ncia no diagn&#243;stico e tratamento desse grupo de pacientes, melhorando com isso o acompanhamento cl&#237;nico dessas popula&#231;&#227;o.</p>
    <p>
      <fn id="end" fn-type="corresp">
        <label>
          <bold>Correspond&#234;ncia:</bold>
        </label>
        <p> Claudio Magalh&#227;es Rangel </p>
        <p> Rua Itapeva, 240 </p>
        <p> 01332-000 &#150; S&#227;o Paulo, SP </p>
        <p> E-mail: </p>
        <p>
          <email xlink:href="cmsrangel@terra.com.br">cmsrangel@terra.com.br</email>
        </p>
      </fn>
    </p>
    <p>Recebido em 13/10/04 </p>
    <p> Aceito em 17/03/06</p>
  </body>
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        <mixed-citation>41. Meade TW, North WRS, Chakrabarti R. Haemostatic    function and cardiovascular death: early results of a prospective study. Lancet 1980;v.i:1050-4.</mixed-citation>
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              <surname>Meade</surname>
              <given-names>TW</given-names>
            </name>
            <name>
              <surname>North</surname>
              <given-names>WRS</given-names>
            </name>
            <name>
              <surname>Chakrabarti</surname>
              <given-names>R</given-names>
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        <mixed-citation>42. Cremer P, Najel D, Labrot B. Lipoprotein    Lp(a) as predictor of myocardial infarction in comparision to fibrinogen , LDL    cholesterol and other risk factors: results from the prospective Gottingen Risk    Incidence and Prevalence Study (Grips). Eur J Clin Invest 1994;24:444-531.</mixed-citation>
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          <article-title>Lipoprotein Lp(a) as predictor of myocardial infarction in comparision to fibrinogen , LDL cholesterol and other risk factors: results from the prospective Gottingen Risk Incidence and Prevalence Study (Grips)</article-title>
          <source>Eur J Clin Invest</source>
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            <year>1994</year>
          </date>
          <fpage>444</fpage>
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            <name>
              <surname>Cremer</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Najel</surname>
              <given-names>D</given-names>
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  </back>
  <sub-article article-type="translation" id="TRen" xml:lang="en">
    <front-stub>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Original Articles</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title xml:lang="en">Aortic stenosis and coronary disease: analysis of risk factors</article-title>
      </title-group>
      <abstract xml:lang="en">
        <p>OBJECTIVE: To analyze clinical laboratorial aspects of the presence of coronary disease in patients with aortic stenosis and evaluate the influence of risk factors in the development of obstructive coronary disease. METHODS: We studied 65 patients who had severe aortic stenosis with an indication for surgery, ages 51 to 85 years, 40 of them women. The coronary angiography assessment resulted in two groups: 26 (40%) with obstructive coronary disease and 39 (60%) with no coronary artery lesion. Personal antecedents for coronary disease (smoking, dyslipidemia, diabetes mellitus, arterial hypertension, family antecedents, sedentarism, and alcoholism) were analyzed. Additionally, the following assessments were made: electrocardiogram, echocardiogram with Doppler, and laboratory tests (blood glucose, total cholesterol and fractions, triglycerides, Apo-A1 and B, fibrinogen, lipoprotein (a) and fraction of triglycerides and cholesterol removal in both groups. RESULTS: In the age analysis, the group with obstructive coronary disease belonged to an older age range with statistical significance (p&lt;0.0001). Signs of ischemia of the anterior wall identified on the electrocardiogram showed a significant relationship with the obstruction of an anterior interventricular artery (p&lt;0.002). The univariate analysis showed a significant difference between the groups regarding averages of the aortic (p= 0.041), HDL (p=0.042), and fibrinogen (p=0.047) gradients. The group with coronary disease presented an average gradient and HDL level lower than the group without obstructive coronary disease. For the fibrinogen variable, the average in the group with no coronary disease was lower compared to that of the coronariopathy group. The multivariate logistic regression analysis showed fibrinogen levels as an independent variable for coronary disease (p&lt;0.039). CONCLUSION: Fibrinogen was an independent risk factor for the association between obstructive coronary disease and aortic stenosis.</p>
      </abstract>
      <kwd-group xml:lang="en">
        <kwd>Stenosis of aortic valve</kwd>
        <kwd>coronary artery disease</kwd>
        <kwd>risk factors</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <p>
        <bold>ORIGINAL ARTICLE</bold>
      </p>
      <p>Aortic stenosis and coronary disease. Analysis of risk factors </p>
      <p>
        <bold>Claudio Magalh&#227;es Rangel; Max Grinberg; Raul Cavalcante Maranh&#227;o; Laura In&#234;s Ventura</bold>
      </p>
      <p>Instituto do Cora&#231;&#227;o do Hospital das Cl&#237;nicas &#150; FMUSP - S&#227;o Paulo, SP - Brazil</p>
      <p>
        <xref ref-type="corresp" rid="end-body2">Mailing Address</xref>
      </p>
      <p>
        <bold>ABSTRACT</bold>
      </p>
      <p><bold>OBJECTIVE: </bold>To analyze clinical laboratorial aspects of the presence of coronary disease in patients with aortic stenosis and evaluate the influence of risk factors in the development of obstructive coronary disease.</p>
      <p><bold>METHODS:</bold> We studied 65 patients who had severe aortic stenosis with an indication for surgery, ages 51 to 85 years, 40 of them women. The coronary angiography assessment resulted in two groups: 26 (40%) with obstructive coronary disease and 39 (60%) with no coronary artery lesion. Personal antecedents for coronary disease (smoking, dyslipidemia, diabetes mellitus, arterial hypertension, family antecedents, sedentarism, and alcoholism) were analyzed. Additionally, the following assessments were made: electrocardiogram, echocardiogram with Doppler, and laboratory tests (blood glucose, total cholesterol and fractions, triglycerides, Apo-A1 and B, fibrinogen, lipoprotein (a) and fraction of triglycerides and cholesterol removal in both groups.</p>
      <p><bold>RESULTS:</bold> In the age analysis, the group with obstructive coronary disease belonged to an older age range with statistical significance (p&lt;0.0001). Signs of ischemia of the anterior wall identified on the electrocardiogram showed a significant relationship with the obstruction of an anterior interventricular artery (p&lt;0.002). The univariate analysis showed a significant difference between the groups regarding averages of the aortic (p= 0.041), HDL (p=0.042), and fibrinogen (p=0.047) gradients. The group with coronary disease presented an average gradient and HDL level lower than the group without obstructive coronary disease. For the fibrinogen variable, the average in the group with no coronary disease was lower compared to that of the coronariopathy group. The multivariate logistic regression analysis showed fibrinogen levels as an independent variable for coronary disease (p&lt;0.039).</p>
      <p><bold>CONCLUSION:</bold> Fibrinogen was an independent risk factor for the association between obstructive coronary disease and aortic stenosis.</p>
      <p><bold>Key words: </bold>Stenosis of aortic valve, coronary artery disease, risk factors.</p>
      <p>Aortic stenosis in adults is characterized by degenerative alterations of the valve leaflets that encumber the proper emptying of the left ventricle, leading to the development of muscular hypertrophy because of chronic and progressive pressure overload of the left ventricle. The main causes of aortic stenosis are congenital, rheumatic, and degenerative or senile.</p>
      <p>The expression "risk factor"<sup>1</sup> describes characteristics that may be found in healthy individuals, which are independently associated with the manifestation of a given disease. In this sense, a risk factor can be defined as any measurable trait or characteristic in an individual that may lead to a greater probability of his manifesting a certain disease<sup>2</sup>.</p>
      <p>A meta-analysis of 33 studies showed a 37% prevalence of coronary disease in patients with calcified aortic stenosis<sup>3</sup>. There are still unanswered questions concerning risk factors for coronary artery disease in aortic stenosis patients. In the analysis of risk factors for coronary disease, it is not possible to assert what degree of participation these factors have in the development of coronary disease associated with aortic stenosis. In analyzing risk factors in an aortic stenosis patient, it would be extremely important from a clinical point of view to know the probability of this patient presenting an associated coronary disease. The answers to these questions could help in identifying the probability of the aortic stenosis patient also bearing an associated coronariopathy. We could determine the participation of each risk factor, alone or in combination, in the development of coronary disease in aortic stenosis patients and diminish the morbidity/mortality of this association.</p>
      <p>
        <bold>METHODS</bold>
      </p>
      <p>Sixty-five patients participated in this research, 40 (61.5%) females, and 25 (38.5%) males. Patients were enrolled in the protocol according to the following inclusion criteria: presence of severe aortic stenosis, absence of any other valve disorder, age greater than or equal to 50 years, no previous cardiac surgery, and absence of clinically significant renal, hepatic, hemic, or neoplastic disease.</p>
      <p>For each patient selected for the protocol, a case report form was completed that included age, gender, body mass index, risk factors for coronary disease, anamnesis data, electrocardiogram, and echocardiogram with Doppler. At the end of the interview, dates were scheduled for laboratory tests and cardiac catheterism.</p>
      <p>In the body mass index evaluation, anthropometric measurements of weight and height were used for the Body Mass Index (BMI) calculation using the formula BMI = weight (Kg) / height2 (m<sup>2</sup>)<sup>4</sup>.</p>
      <p>Selected risk factors were smoking (habit of smoking more than five cigarettes a day for at least six months)<sup>5</sup>, HDL-cholesterol under 35 mg/dL, LDL-cholesterol over 130 mg/dL<sup>6</sup>, diabetes mellitus (blood glucose levels over 140 mg/dL after 12-hour overnight fast)<sup>7</sup>, systemic arterial hypertension (patients with systolic arterial pressure over 150 mmHg and diastolic pressure over 90 mmHg)<sup>8</sup>, family antecedents (parents or siblings with history of coronary disease, and ages less than 55 years of age for men and less than 65 years of age for women)<sup>2</sup>, sedentarism (patients who reported activities such as walking less than 30 minutes a week or sporadic participation in sports)<sup>2</sup>, and alcoholism (men with intake of more than 4 doses a day or more than 20 doses a week and women with intake of more than 3 doses a day or more than 12 doses a week)<sup>2</sup>. </p>
      <p>Anamnesis data were defined by functional class according to the New York Heart Association classification<sup>9</sup>, angina by the Canadian Cardiovascular Society<sup>10</sup>, syncope and symptoms and signs compatible with congestive heart failure.</p>
      <p>A 12-lead electrocardiogram was performed on all patients using Hewlett Packard equipment, model 1700, according to conventional criteria. Since there are classic electrocardiographic changes in aortic stenosis, we will analyze the association of anterior wall ischemia with significant damage of the anterior descending artery. We will not examine causal relationship with other affected coronary arteries, since they may be confused with the classic eletrocardiographic alterations that are present in severe aortic stenosis.</p>
      <p>The echocardiogram with Doppler was performed on all patients with ATL equipment, HDI 3000 model; the maximal aortic valvar gradient was analyzed by applying BERNOULLI&#146;s modified equation<sup>11</sup>, and the ejection fraction (EF) of the left ventricle by means of the Cube Method<sup>12,13</sup>. </p>
      <p>Blood test samples were drawn in the morning after a 12-hour fast. Measurements of blood glucose, triglycerides, total cholesterol and fractions, fibrinogen, apoA1, apoB and Lp (a) were carried out by the Clinical Laboratory of the Heart Institute. Also included in this study were the plasma removal kinetics of artificial chylomicrons, and this exam was performed by the Lipids Laboratory of the Heart Institute.</p>
      <p>Cardiac catheterism was performed on all patients enrolled in the study as a pre-operative test in order to analyze coronary anatomy and evaluate the need for myocardial revascularization associated to aortic valve replacement. The test was carried out using the SONES and SHIREY technique<sup>14</sup>. Subjects were considered coronary patients when they had at least one subepicardial artery with an atherosclerotic process causing more than 50% reduction of the vessel lumen in comparison to the closest normal segment. </p>
      <p>The classification variables are presented descriptively on tables containing absolute (n) and relative (%) frequencies. The associations between these variables and the presence of coronary disease will be compared using the chi-square test, verisimilitude ratio test, or Fisher&#146;s exact test<sup>15</sup>. For the analysis of the incidence of coronary disease by age bracket, the ratio of verisimilitude test was used<sup>15</sup>.</p>
      <p>Continuous variables are presented descriptively in tables containing means and standard deviation. The means of these variables as to the presence of coronary disease were compared with Student&#146;s t-test<sup>16</sup>. Gradient, blood glucose, triglycerides, Lp (a), and FTR (Ch) variables were submitted to logarithmic transformation for parameter analysis. </p>
      <p>Variables that showed statistical significance in the univariate analysis were used for the adjustment of a multiple logistic regression model with a stepwise variable selection procedure<sup>16</sup>. </p>
      <p>P values of p &lt; 0.05 were considered significant.</p>
      <p>
        <bold>RESULTS</bold>
      </p>
      <p>Ages of the 65 patients who participated in the study varied between 51 and 85 years (mean 68), and 40 (61.5%) of the subjects were women. Coronary angiography resulted in 26 (40%) patients with obstructive coronary disease and 39 (60%) without obstructive coronary disease. </p>
      <p>We observed a greater proportion of coronary disease incidences in the older age ranges. There was a difference (p&lt;0.0001) between the age brackets, i.e., the 71-80 year range had a larger proportion of patients with disease than the other age ranges.</p>
      <p>A correlation between anterior ischemia seen on the electrocardiogram and damage of the anterior interventricular artery was observed. Of the 17 patients with lesions in this artery, 11 showed signs of anterior ischemia on the electrocardiogram (64.71%) with p&lt;0.002 (Fisher&#146;s test). There was no significant association between the groups with and without coronary disease as to gender, number of risk factors, family antecedents, systemic arterial hypertension, diabetes mellitus, dyslipidemia, smoking, sedentarism, and alcoholism. No significant association was noted between the groups with and without coronary disease as to functional class, angina, syncope, and heart failure.</p>
      <p>We did observe a significant difference between the groups in term of means of the maximal gradient (p = 0.041), HDL cholesterol (p = 0.042), and fibrinogen (p = 0.047) variables. Patients with coronary disease had lower values for the mean gradient and HDL than those without coronary disease. With the fibrinogen variable, patients without coronary disease had lower mean levels when compared to those with coronary disease as is shown on <xref ref-type="table" rid="tab01-body2">Table 1</xref>.</p>
      <table-wrap id="tab01-body2">
        <graphic xlink:href="1678-4170-abc-87-02-0115-00008-gt01-en.jpg"/></table-wrap>
      <p>The influence of the parameters analyzed in the presence of coronary disease is described on <xref ref-type="table" rid="tab02-body2">Table 2</xref>. Only fibrinogen exerted a significant influence (p = 0.039) on the presence of coronary disease.</p>
      <table-wrap id="tab02-body2">
        <graphic xlink:href="1678-4170-abc-87-02-0115-00008-gt02-en.jpg"/></table-wrap>
      <p>For the presence of coronary disease in the logistic regression model, the explanatory variables gradient, HDL, and fibrinogen were considered. These variables showed statistical significance in the univariate analysis. After the stepwise selection of variables, the fibrinogen variable showed significance. <xref ref-type="table" rid="tab02-body2">Table 2</xref> shows that the estimated parameter for fibrinogen is positive, indicating a positive correlation as to the probability of coronary disease (the greater the value of fibrinogen, the greater the probability of coronary disease). </p>
      <p><xref ref-type="fig" rid="qdr01-body2">Chart 1</xref> shows the distribution of sensitivity and specificity values for different coronary disease probabilities. The maximum value point for both indices is the probability value of 0.42. </p>
      <fig id="qdr01-body2">
        <graphic xlink:href="1678-4170-abc-87-02-0115-00008-gf01-en.jpg"/></fig>
      <p>A 0.42 probability corresponds to a fibrinogen value of 370, that is, if the patients with values over 370 are classified as coronary patients and those with values under 370 are considered not ill, we have a 57.7% sensitivity and a 63.2% specificity (<xref ref-type="fig" rid="qdr01-body2">Charts 1</xref> and <xref ref-type="fig" rid="qdr02-body2">2</xref>)</p>
      <fig id="qdr02-body2">
        <graphic xlink:href="1678-4170-abc-87-02-0115-00008-gf02-en.jpg"/></fig>
      <p>
        <bold>DISCUSSION</bold>
      </p>
      <p>The incidence of coronary disease in patients submitted to aortic valve replacement is estimated between 7% and 66%<sup>17,18</sup>. A meta-analysis with 33 studies showed a 37% prevalence of coronary disease in patients with calcified aortic stenosis<sup>3</sup>. In our series, the 40% prevalence of coronary disease proved to be within the average of the above mentioned range, as had also been verified in well-conducted studies performed by LUND et al<sup>19</sup> Mautner et al<sup>20</sup> and Paquay et al<sup>21</sup>.</p>
      <p>The average age of 70 years was similar to those noted by other authors such as VEKSHTEIN<sup>22</sup> and BESSONE<sup>23</sup>. In our series, the age mean did not show a statistical difference between the two groups in spite of the older age range in the coronariopathy patients. A certain correlation was observed between age and coronariopathy rate, where the older age bracket has a greater probability of coronary disease associated with aortic stenosis<sup>22,23</sup>. Our highest age mean is in agreement with that found in most medical literature. </p>
      <p>The presence of coronary disease in patients with aortic stenosis has been the focus of many studies, and some have suggested a correlation between risk factors and the presence of coronary disease in aortic valve disease patients<sup>18,24-26</sup>. The participation of risk factors for coronary disease has not been adequately appreciated as a predictive factor of coronary disease in patients with aortic stenosis<sup>18,24,26,27</sup>. In some studies, the absence of risk factors and angina were sufficient to exclude coronary disease associated with valve disorders<sup>26</sup>. On the other hand, Acar et al<sup>28</sup> and Pluta et al<sup>18</sup> found a high risk factor incidence in patients with coronary disease associated with aortic stenosis, while Carstens et al<sup>29</sup> and Exadactylos et al<sup>30</sup> did not observe a correlation between the presence of risk factors and the incidence of coronary disease associated with aortic stenosis. In our group of patients, the greater number of risk factors did not increase the incidence of coronary disease, a fact that concurs with the studies of Carstens<sup>29</sup> and Exadactylos<sup>30</sup>.</p>
      <p>Some authors<sup>24,31,32</sup> have observed that the aortic gradient tends to be smaller in patients with than in those without angina, especially when the angina is severe. This observation may be caused by the great prevalence of coronary disease associated with moderate aortic stenosis. Berndt et al<sup>33</sup> demonstrated that the aortic gradient was smaller in patients that had coronary disease, which was also a result noted in our study. Several authors<sup>18,24,28,31,32</sup> had this same result, which raises the hypothesis that myocardial ischemia or infarct could potentially diminish the gradient through the aortic valve. </p>
      <p>Several studies in literature<sup>34-38</sup> observed that reduced levels of HDL-c increase the risk of coronary disease, especially if triglyceride levels are also elevated. Our study showed higher HDL-c levels in patients with aortic stenosis without coronary disease, reinforcing the concept of a protection factor for coronary disease. This aspect identified in our study is an important point because, when faced by a given patient&#146;s situation, it allows us, along with other factors, to determine the probability of his presenting coronary disease associated with aortic stenosis.</p>
      <p>The level of plasmatic fibrinogen has been shown to be a predictor of coronary disease in several prospective studies<sup>39,40</sup>. Seven prospective studies<sup>41,42</sup> have noted an increase in the incidence of coronary disease when fibrinogen levels are high. The participation of fibrinogen as a risk factor in the coronary disease of a patient with a valve disorder has not yet been reported in literature. </p>
      <p>In our research, this correlation was statistically significant on the univariate analysis (<xref ref-type="table" rid="tab01-body2">Table 1</xref>) and on the logistic regression model (<xref ref-type="table" rid="tab02-body2">Table 2</xref>). We studied it as an important factor in analyzing the probability of a patient with aortic stenosis having an associated coronary disease, since with the progressive increase of fibrinogen levels, the probability of this association also rises (<xref ref-type="fig" rid="qdr02-body2">Chart 2</xref>).</p>
      <p>In conclusion, the observation of fibrinogen levels in clinical practice may be indicative of the increased prevalence of obstructive coronary disease in patients with aortic stenosis. This result was seen in our research, where the level of fibrinogen was an independent risk factor for the association of obstructive coronary disease and aortic stenosis, as the highest levels increased the probability of this association. This aspect, along with an analysis of the aortic gradient, age range, electrocardiogram, and HDL-c level, may be extremely important in the diagnosis and treatment of this group of patients, improving the clinical follow-up of this population. </p>
      <p>
        <bold>REFERENCES</bold>
      </p>
      <p>
        <fn id="end-body2" fn-type="corresp">
          <p>Mailing Address:</p>
          <p> Claudio Magalh&#227;es Rangel</p>
          <p> Rua Itapeva, 240</p>
          <p> 01332-000 &#150; S&#227;o Paulo, SP - Brazil</p>
          <p> E-mail: </p>
          <p>
            <email xlink:href="cmsrangel@terra.com.br">cmsrangel@terra.com.br</email>
          </p>
        </fn>
      </p>
      <p>Received on 10/13//04</p>
      <p> Accepted on 03/17/06</p>
    </body>
  </sub-article>
</article>
