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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">Y4pndwYZRFxgL4tHYk3MQDw</article-id>
      <article-id pub-id-type="other">00006</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v2">S0066-782X2008000200006</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v1">S0066-782X(08)09000206</article-id>
      <article-id pub-id-type="doi">10.1590/S0066-782X2008000200006</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Artigos Originais</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Dosagem de microalbumin&#250;ria em hipertensos e em pacientes portadores de doen&#231;a coronariana</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Silva</surname>
            <given-names>Ricardo Pereira</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Cisne</surname>
            <given-names>Karinne</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Oliveira</surname>
            <given-names>Jerusa Mara de</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Kubrusly</surname>
            <given-names>Marcos</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Rodrigues Sobrinho</surname>
            <given-names>Carlos Roberto Martins</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Andrade</surname>
            <given-names>Pedro Jos&#233; Negreiros de</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
      </contrib-group>
      <aff id="aff01">
        <addr-line>
          <named-content content-type="city">Fortaleza</named-content>
          <named-content content-type="state"/>
        </addr-line>
        <institution content-type="orgname">Universidade Federal do Cear&#225;</institution>
        <country country="BR">Brazil</country>
      </aff>
      <pub-date date-type="collection" publication-format="electronic">
        <month>02</month>
        <year>2008</year>
      </pub-date>
      <volume>90</volume>
      <issue>2</issue>
      <fpage>108</fpage>
      <lpage>113</lpage>
      <history>
        <date date-type="accepted">
          <day>15</day>
          <month>10</month>
          <year>2007</year>
        </date>
        <date date-type="rev-recd">
          <day>22</day>
          <month>06</month>
          <year>2007</year>
        </date>
        <date date-type="received">
          <day>07</day>
          <month>05</month>
          <year>2007</year>
        </date>
      </history>
      <permissions>
        <license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by-nc/4.0/" xml:lang="en">
          <license-p>This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.</license-p>
        </license>
      </permissions>
      <abstract>
        <p>FUNDAMENTO: A taxa normal de excre&#231;&#227;o de albumina em 24 horas &#233; de 20 mg. A taxa persistente de 30 a 300 mg/dia &#233; chamada de microalbumin&#250;ria (MA) e est&#225; relacionada com maior preval&#234;ncia de doen&#231;a cardiovascular. OBJETIVO: Determinar a preval&#234;ncia de microalbumin&#250;ria em um grupo de hipertensos e em um grupo de portadores de doen&#231;a coronariana; e determinar a rela&#231;&#227;o da presen&#231;a de microalbumin&#250;ria com hipertens&#227;o arterial, diabete melitus, dislipidemia, tabagismo e obesidade. M&#201;TODOS:: Determinamos a presen&#231;a de microalbumin&#250;ria num grupo de hipertensos (73 indiv&#237;duos) e num grupo de coronariopatas (39 indiv&#237;duos), e comparamos com um grupo-controle (43 indiv&#237;duos). Considerou-se como microalbumin&#250;ria a rela&#231;&#227;o albumina/creatinina maior que 30 e menor que 300 em amostra isolada de urina matinal. Na an&#225;lise estat&#237;stica, foram utilizados os testes do qui-quadrado e o teste exato de Fisher. RESULTADOS: A microalbumin&#250;ria esteve presente em 9,5% dos hipertensos, em 33% dos coronariopatas e n&#227;o esteve presente em nenhum indiv&#237;duo do grupo-controle. Ao analisar a ocorr&#234;ncia de microalbumin&#250;ria segundo os diversos par&#226;metros cl&#237;nicos, independentemente do grupo a que pertenciam, verificamos correla&#231;&#227;o estatisticamente significativa com idade, diabete e dislipidemia. CONCLUS&#195;O: 1) A preval&#234;ncia de microalbumin&#250;ria em indiv&#237;duos hipertensos &#233; elevada, sendo ainda mais elevada em portadores de doen&#231;a coronariana; 2) existe correla&#231;&#227;o da presen&#231;a de microalbumin&#250;ria com idade, diabete e dislipidemia.</p>
      </abstract>
      <kwd-group xml:lang="pt" kwd-group-type="author-generated">
        <kwd>Albumin&#250;ria</kwd>
        <kwd>hipertens&#227;o</kwd>
        <kwd>coronariopatia</kwd>
      </kwd-group>
      <pub-date publication-format="electronic" date-type="pub">
        <day>28</day>
        <month>04</month>
        <year>2008</year>
      </pub-date>
    </article-meta>
  </front>
  <body>
    <p>
      <bold>ARTIGOS ORIGINAIS</bold>
    </p>
    <p>Dosagem de microalbumin&#250;ria em hipertensos e em pacientes portadores de doen&#231;a coronariana</p>
    <p>
      <bold>Ricardo Pereira Silva; Karinne Cisne; Jerusa Mara de Oliveira; Marcos Kubrusly; Carlos Roberto Martins Rodrigues Sobrinho; Pedro Jos&#233; Negreiros de Andrade</bold>
    </p>
    <p>Hospital Universit&#225;rio Walter Cant&#237;dio, Fortaleza, CE - Brasil</p>
    <p>
      <xref ref-type="corresp" rid="end">Correspond&#234;ncia</xref>
    </p>
    <p>
      <bold>RESUMO</bold>
    </p>
    <p><bold>FUNDAMENTO:</bold> A taxa normal de excre&#231;&#227;o de albumina em 24 horas &#233; de 20 mg. A taxa persistente de 30 a 300 mg/dia &#233; chamada de microalbumin&#250;ria (MA) e est&#225; relacionada com maior preval&#234;ncia de doen&#231;a cardiovascular. </p>
    <p><bold>OBJETIVO:</bold> Determinar a preval&#234;ncia de microalbumin&#250;ria em um grupo de hipertensos e em um grupo de portadores de doen&#231;a coronariana; e determinar a rela&#231;&#227;o da presen&#231;a de microalbumin&#250;ria com hipertens&#227;o arterial, diabete melitus, dislipidemia, tabagismo e obesidade. </p>
    <p><bold>M&#201;TODOS:</bold>: Determinamos a presen&#231;a de microalbumin&#250;ria num grupo de hipertensos (73 indiv&#237;duos) e num grupo de coronariopatas (39 indiv&#237;duos), e comparamos com um grupo-controle (43 indiv&#237;duos). Considerou-se como microalbumin&#250;ria a rela&#231;&#227;o albumina/creatinina maior que 30 e menor que 300 em amostra isolada de urina matinal. Na an&#225;lise estat&#237;stica, foram utilizados os testes do qui-quadrado e o teste exato de Fisher. </p>
    <p><bold>RESULTADOS:</bold> A microalbumin&#250;ria esteve presente em 9,5% dos hipertensos, em 33% dos coronariopatas e n&#227;o esteve presente em nenhum indiv&#237;duo do grupo-controle. Ao analisar a ocorr&#234;ncia de microalbumin&#250;ria segundo os diversos par&#226;metros cl&#237;nicos, independentemente do grupo a que pertenciam, verificamos correla&#231;&#227;o estatisticamente significativa com idade, diabete e dislipidemia. </p>
    <p><bold>CONCLUS&#195;O:</bold> 1) A preval&#234;ncia de microalbumin&#250;ria em indiv&#237;duos hipertensos &#233; elevada, sendo ainda mais elevada em portadores de doen&#231;a coronariana; 2) existe correla&#231;&#227;o da presen&#231;a de microalbumin&#250;ria com idade, diabete e dislipidemia. (Arq Bras Cardiol 2008; 90(2): 108-113)</p>
    <p><bold>Palavras-chave:</bold> Albumin&#250;ria/complica&#231;&#245;es, hipertens&#227;o, coronariopatia.</p>
    <p>
      <bold>Introdu&#231;&#227;o</bold>
    </p>
    <p>A taxa normal de excre&#231;&#227;o de albumina em 24 horas &#233; de 20 mg. A taxa persistente de 30 a 300 mg/dia &#233; chamada de microalbumin&#250;ria (MA).</p>
    <p>A coleta de urina de 24 horas &#233; o m&#233;todo padr&#227;o para a detec&#231;&#227;o de microalbumin&#250;ria, embora sua detec&#231;&#227;o tamb&#233;m possa ser realizada com a coleta da primeira mic&#231;&#227;o do dia<sup>1-2</sup>. </p>
    <p>O efeito do volume pode ser evitado pelo c&#225;lculo da rela&#231;&#227;o albumina/creatinina, numa amostra de urina<sup>3</sup>.</p>
    <p>As tr&#234;s grandes limita&#231;&#245;es para a dosagem de microalbumin&#250;ria s&#227;o: exerc&#237;cios vigorosos que podem causar aumento transit&#243;rio na excre&#231;&#227;o de albumina<sup>4</sup>; altera&#231;&#227;o, durante o dia, na rela&#231;&#227;o entre a coleta de uma &#250;nica mic&#231;&#227;o e a coleta de 24 horas, a correla&#231;&#227;o &#233; melhor se as amostras s&#227;o obtidas no meio da manh&#227;<sup>5</sup>; a precis&#227;o da rela&#231;&#227;o albumina/creatinina diminui se a excre&#231;&#227;o de creatinina for muito diferente do valor estimado, como ocorre em homens muito musculosos ou em indiv&#237;duos caqu&#233;ticos<sup>6</sup>.</p>
    <p>Estudos preliminares demonstraram que a microalbumin&#250;ria representava a manifesta&#231;&#227;o cl&#237;nica mais precoce da nefropatia diab&#233;tica, e sua dosagem passou a ser recomendada para a avalia&#231;&#227;o inicial e para o acompanhamento em diab&#233;ticos.</p>
    <p>Estudos posteriores demonstraram que havia associa&#231;&#227;o entre microalbumin&#250;ria e doen&#231;a cardiovascular tanto em diab&#233;ticos quanto em n&#227;o-diab&#233;ticos. </p>
    <p>O estudo HOPE mostrou que a presen&#231;a de microalbumin&#250;ria estava associada ao aumento do risco relativo de desfechos prim&#225;rios (infarto do mioc&#225;rdio, AVC ou morte cardiovascular). O risco de um evento cardiovascular adverso aumentou progressivamente com o aumento dos n&#237;veis de microalbumin&#250;ria<sup>7</sup>.</p>
    <p>Numa an&#225;lise posterior do estudo LIFE, com hipertensos com evid&#234;ncia eletrocardiogr&#225;fica de hipertrofia do ventr&#237;culo esquerdo, foi observado que, para cada aumento de 10 vezes na rela&#231;&#227;o albumina/creatinina, o risco de infarto ou AVC aumentou em 57% e o risco de morte cardiovascular em 98% para pacientes n&#227;o-diab&#233;ticos. Os respectivos aumentos nos diab&#233;ticos foram de 39% e 47%<sup>8</sup>.</p>
    <p>Numa an&#225;lise do estudo PREVEND, observou-se um aumento no risco relativo de mortalidade cardiovascular de 1,35 para cada duplica&#231;&#227;o do valor da albumin&#250;ria<sup>9</sup>.</p>
    <p>Em indiv&#237;duos idosos, a combina&#231;&#227;o de microalbumin&#250;ria e hiperinsulinemia, um reflexo da resist&#234;ncia &#224; insulina, est&#225; associada com aumento no risco de eventos e mortalidade coronariana<sup>10</sup>.</p>
    <p>Mesmo n&#237;veis extremamente baixos de microalbumin&#250;ria podem estar associados a aumento no risco cardiovascular, como mostra o Estudo do Cora&#231;&#227;o da Cidade de Copenhague. Pacientes com albumin&#250;ria superior a 6,9 mg/dia tiveram um risco relativo de morte de 1,9 e risco de doen&#231;a coronariana de 2,0<sup>11</sup>.</p>
    <p>Ainda n&#227;o se conhece o mecanismo que explica a associa&#231;&#227;o entre microalbumin&#250;ria e doen&#231;a cardiovascular. A microalbumin&#250;ria em n&#227;o-diab&#233;ticos parece ser um sinal dos rins de que a vasculatura, principalmente do endot&#233;lio, n&#227;o est&#225; funcionando adequadamente. Esse fato pode ser comprovado pelas seguintes evid&#234;ncias: 1) a vasodilata&#231;&#227;o em resposta a alguns est&#237;mulos est&#225; reduzida em indiv&#237;duos idosos normais com microalbumin&#250;ria quando comparados aos que n&#227;o apresentam microalbumin&#250;ria<sup>12</sup>; 2) entre os hipertensos n&#227;o-diab&#233;ticos, aqueles com microalbumin&#250;ria apresentaram n&#237;veis mais elevados do fator de von Willebrand do que aqueles sem microalbumin&#250;ria; como o fator de von Willebrand tem sido associado a trombose oclusiva, o aumento desse fator pode contribuir para o aumento da doen&#231;a cardiovascular<sup>13</sup>.</p>
    <p>Entre os hipertensos n&#227;o-diab&#233;ticos, a microalbumin&#250;ria est&#225; associada com maiores n&#237;veis de press&#227;o, maiores n&#237;veis de colesterol e menores n&#237;veis de HDL<sup>14</sup>. </p>
    <p>Os objetivos deste trabalho s&#227;o: determinar a preval&#234;ncia de microalbumin&#250;ria em um grupo de hipertensos e em um grupo de portadores de doen&#231;a coronariana, e determinar a rela&#231;&#227;o da presen&#231;a de microalbumin&#250;ria com hipertens&#227;o arterial, diabete melito, dislipidemia, tabagismo e obesidade.</p>
    <p>
      <bold>Material e m&#233;todo</bold>
    </p>
    <p>
      <bold>Pacientes</bold>
    </p>
    <p><italic>Crit&#233;rios de inclus&#227;o -</italic> pacientes hipertensos e portadores de doen&#231;a coronariana atendidos no Hospital Universit&#225;rio Walter Cant&#237;dio. Como grupo-controle, utilizamos funcion&#225;rios saud&#225;veis do mesmo hospital.</p>
    <p> Consideramos hipertensos os indiv&#237;duos com tr&#234;s ou mais medidas de press&#227;o arterial maiores ou igual a 140/90 mmHg, ou que tinham previamente o diagn&#243;stico de hipertens&#227;o arterial e estavam usando anti-hipertensivos. Foram considerados diab&#233;ticos os indiv&#237;duos com pelo menos duas medidas de glicemia em jejum superiores a 125 mg/dl ou que estavam em tratamento para diabetes com hipoglicemiante oral e/ou insulina. Dislipid&#234;micos, os pacientes que apresentaram n&#237;veis de colesterol superior a 200 mg/dl ou triglic&#233;rides superior a 150 mg/dl ou que estavam em tratamento com drogas hipolipemiantes. Foram considerados tabagistas os indiv&#237;duos que fumaram qualquer quantidade de cigarros no &#250;ltimo ano.</p>
    <p>No grupo de doen&#231;a coronariana, inclu&#237;ram-se os pacientes com comprova&#231;&#227;o angiogr&#225;fica de les&#227;o severa (estenose &gt; 70%) em pelo menos uma coron&#225;ria.</p>
    <p><italic>Crit&#233;rios de exclus&#227;o -</italic> foram exclu&#237;dos os pacientes com creatinina superior a 2 mg/dl.</p>
    <p>
      <bold>M&#233;todos</bold>
    </p>
    <p>Depois da medida do peso e aferi&#231;&#227;o da altura, calculou-se o &#237;ndice de massa corp&#243;rea (IMC) pela f&#243;rmula: IMC = Peso/altura<sup>2</sup>. Consideraram-se os seguintes aspectos: sobrepeso com IMC maior ou igual a 25 e obeso com IMC maior ou igual a 30.</p>
    <p>Mediu-se a circunfer&#234;ncia abdominal, que foi considerada aumentada quando maior que 80 cm em mulheres ou maior que 90 cm em homens.</p>
    <p>Considerou-se microalbumin&#250;ria a rela&#231;&#227;o albumina/creatinina maior que 30 em amostra isolada de urina matinal.</p>
    <p>
      <bold>An&#225;lise Estat&#237;stica</bold>
    </p>
    <p>A compara&#231;&#227;o do grupo portador de hipertens&#227;o arterial sist&#234;mica (HAS) e do grupo portador de doen&#231;a arterial coronariana (DAC) com o grupo-controle, segundo os diversos par&#226;metros, cl&#237;nicos foi realizada utilizando-se o teste do qui-quadrado e o teste exato de Fisher.</p>
    <p>Para determinar se a incid&#234;ncia de MA entre os pacientes com DAC era diferente da incid&#234;ncia entre os pacientes com HAS e entre os indiv&#237;duos do grupo-controle, utilizamos a an&#225;lise de propor&#231;&#245;es, com o teste para propor&#231;&#227;o amostral (binomial).</p>
    <p>Para aferir a suposta import&#226;ncia da microalbumin&#250;ria, do IMC, da circunfer&#234;ncia abdominal, do tabagismo, da dislipidemia, do diabete melito e da hipertens&#227;o arterial como fatores determinantes da doen&#231;a arterial coronariana, os tr&#234;s grupos originais (DAC, HAS e controle) foram reunidos para servir como base de uma an&#225;lise multivariada log&#237;stica. Para que isso fosse poss&#237;vel, os pacientes de cada grupo receberam as vari&#225;veis auxiliares necess&#225;rias para marcar sua filia&#231;&#227;o original. Considerando a doen&#231;a arterial coronariana como vari&#225;vel dependente e todas as outras citadas anteriormente como independentes, iniciou-se a procura pelo modelo mais apropriado. Partiu-se de um modelo que contemplava todas as vari&#225;veis independentes, e usaram-se as t&#233;cnicas tradicionais de inser&#231;&#227;o e elimina&#231;&#227;o de vari&#225;veis.</p>
    <p>Considerou-se como estatisticamente significativo p &lt; 0,05.</p>
    <p>
      <bold>Resultados</bold>
    </p>
    <p>O grupo de hipertensos contou com 73 indiv&#237;duos (23% do sexo masculino), o grupo de coronariopatas com 39 indiv&#237;duos (43% do sexo masculino) e o grupo-controle com 43 indiv&#237;duos (9% do sexo masculino)</p>
    <p>Quando comparamos o grupo de hipertensos com o grupo-controle, observamos que os hipertensos eram mais idosos e mais obesos. Nesse grupo, havia maior propor&#231;&#227;o de diab&#233;ticos, dislipid&#234;micos e portadores de microalbumin&#250;ria. Quando se comparou o grupo de coronariopatas com o grupo-controle, observou-se que os coronariopatas eram predominantemente do sexo masculino e mais idosos. Nesse grupo, verificou-se maior propor&#231;&#227;o de diab&#233;ticos, dislipid&#234;micos e portadores de microalbumin&#250;ria. A microalbumin&#250;ria esteve presente em 9,5% dos hipertensos, em 33% dos coronariopatas e n&#227;o foi constatada em nenhum indiv&#237;duo do grupo-controle (<xref ref-type="table" rid="tab01">tab. 1</xref> e <xref ref-type="fig" rid="fig01">fig. 1</xref>). Ainda quanto &#224; microalbumin&#250;ria, observamos diferen&#231;a estatisticamente significativa quando comparamos o grupo DAC com o grupo controle (p &lt; 0,001), o grupo HAS com o grupo-controle (p &lt; 0,001) e o grupo DAC com o grupo HAS (p &lt; 0,001).</p>
    <table-wrap id="tab01">
      <graphic xlink:href="1678-4170-abc-90-02-0108-00006-gt01.jpg"/></table-wrap>
    <fig id="fig01">
      <graphic xlink:href="1678-4170-abc-90-02-0108-00006-gf01.jpg"/></fig>
    <p>Quando se analisou a ocorr&#234;ncia de microalbumin&#250;ria segundo os diversos par&#226;metros cl&#237;nicos, independentemente do grupo a que os indiv&#237;duos pertenciam, verificamos correla&#231;&#227;o estaticamente significativa com idade, diabete e dislipidemia (<xref ref-type="table" rid="tab02">tab. 2</xref>). Quando analisamos microalbumin&#250;ria com o peso dos indiv&#237;duos, n&#227;o encontramos microalbumin&#250;ria em nenhum dos 37 indiv&#237;duos obesos, mas constatamos microalbumin&#250;ria em 13 dos 67 indiv&#237;duos com sobrepeso (19,4%) e em 7 dos 39 indiv&#237;duos com peso ideal (17,9%). Quando agrupamos os obesos com os indiv&#237;duos com sobrepeso, encontramos preval&#234;ncia de apenas 13%, que &#233; inferior aos indiv&#237;duos com peso ideal.</p>
    <table-wrap id="tab02">
      <graphic xlink:href="1678-4170-abc-90-02-0108-00006-gt02.jpg"/></table-wrap>
    <p>Quando se testou a import&#226;ncia da microalbumin&#250;ria, do IMC, da circunfer&#234;ncia abdominal, do tabagismo, da dislipidemia, do diabete melito e da hipertens&#227;o arterial como fatores determinantes da exist&#234;ncia de doen&#231;a coronariana, observou-se que o diabete melito, a dislipidemia e a microalbumin&#250;ria foram determinantes. Um paciente com microalbumin&#250;ria tem 4,5 vezes mais chance de apresentar doen&#231;a arterial coronariana quando comparado com aquele sem microalbumin&#250;ria. O paciente com diabete melito apresenta 4,3 vezes mais chance, e aquele com dislipidemia tem 4,1 vezes mais chance.</p>
    <p>
      <bold>Discuss&#227;o</bold>
    </p>
    <p>Sabe-se que a microalbumin&#250;ria &#233; um fator de risco para doen&#231;a cardiovascular, mas n&#227;o se sabe se essa associa&#231;&#227;o &#233; devida ao efeito da microalbumin&#250;ria no desenvolvimento da aterosclerose subcl&#237;nica ou se a microalbumin&#250;ria desestabiliza a aterosclerose subcl&#237;nica, levando a eventos cl&#237;nicos. Cao e cols.<sup>15</sup> avaliaram uma popula&#231;&#227;o de 3.312 participantes do "Cardiovascular Health Study" com pesquisa de MA. Os participantes foram divididos em tr&#234;s grupos: indiv&#237;duos sem DM ou HAS (33%), hipertensos (52%), diab&#233;ticos com ou sem HAS (15%). Para cada um dos tr&#234;s grupos, o risco relativo de doen&#231;a cardiovascular na presen&#231;a de MA aumentou 1,7 a 1,8 vezes. No entanto, a MA n&#227;o esteve associada com risco de aterosclerose subcl&#237;nica na aus&#234;ncia de HAS ou DM, o que pode significar que o mecanismo de associa&#231;&#227;o da MA com doen&#231;a cardiovascular envolve desestabiliza&#231;&#227;o do sistema vascular, levando &#224; doen&#231;a clinicamente aparente<sup>15</sup>.</p>
    <p>Segundo Cirillo, o principal correlato da microalbumin&#250;ria &#233; a press&#227;o arterial, sist&#243;lica ou diast&#243;lica. A rela&#231;&#227;o entre press&#227;o arterial e microalbumin&#250;ria &#233; cont&#237;nua e gradual porque a preval&#234;ncia da microalbumin&#250;ria aumenta com a severidade da hipertens&#227;o. Para hipercolesterolemia, tabagismo e diabete, os dados s&#227;o menos contundentes, mas apontam para uma associa&#231;&#227;o positiva independente com microalbumin&#250;ria<sup>16</sup>.</p>
    <p>A preval&#234;ncia de microalbumin&#250;ria em hipertensos em nosso trabalho foi de 9,5%, valor um pouco inferior ao que foi detectado por outros autores<sup>17</sup>.</p>
    <p>A preval&#234;ncia de microalbumin&#250;ria nos nossos pacientes obesos ou com sobrepeso foi de apenas 13%, inferior ao grupo com peso ideal (17,9%). Valensi e cols.<sup>18</sup> encontraram preval&#234;ncia de microalbumin&#250;ria nos obesos de at&#233; 12%. Quando a hipertens&#227;o arterial era associada &#224; obesidade, a preval&#234;ncia chegava at&#233; 19%<sup>18</sup>. Em outro estudo com indiv&#237;duos obesos ou com sobrepeso, a obesidade centr&#237;peta implicou risco 18 vezes maior de microalbumin&#250;ria em rela&#231;&#227;o a indiv&#237;duos magros, enquanto nos obesos com distribui&#231;&#227;o perif&#233;rica o risco foi de 4 vezes<sup>19</sup>. Estudo brasileiro demonstrou tend&#234;ncia a n&#237;veis lim&#237;trofes de microalbumin&#250;ria noturna, mais elevada em obesas normotensas com distribui&#231;&#227;o central de gordura<sup>20</sup>.</p>
    <p>Encontramos em nossos dados alta preval&#234;ncia de microalbumin&#250;ria em pacientes portadores de coronariopatia (33%). Desde a d&#233;cada passada, demonstrou-se a associa&#231;&#227;o de microalbumin&#250;ria com doen&#231;a coronariana, quando Tuttle e cols.<sup>21</sup> estudaram 308 pacientes submetidos a coronariografia, determinando previamente a rela&#231;&#227;o da albumina/creatinina em amostra isolada de urina matinal. A excre&#231;&#227;o de albumina urin&#225;ria (EAU) em pacientes com DAC foi significativamente maior do que nos pacientes sem DAC. A excre&#231;&#227;o da albumina aumentou progressivamente com a severidade da DAC. Em pacientes sem DM, foi observado rela&#231;&#227;o da EAU com DAC, mas ela foi mais pronunciada nos diab&#233;ticos. Em an&#225;lise de regress&#227;o m&#250;ltipla, o risco relativo para DAC severa foi de 2,2 para MA<sup>21</sup>.</p>
    <p>A rela&#231;&#227;o da MA com DAC parece sofrer influ&#234;ncia &#233;tnica. Tillin e cols.<sup>22</sup> estudaram popula&#231;&#227;o londrina composta por 1.460 europeus, 946 asi&#225;ticos e 559 afro-caribenhos e observaram associa&#231;&#227;o de MA com preval&#234;ncia e mortalidade de DAC apenas para homens asi&#225;ticos e mulheres europ&#233;ias. Deve-se ressaltar que, neste trabalho, o crit&#233;rio diagn&#243;stico para DAC &#233; muito discut&#237;vel, pois inclui apenas a hist&#243;ria cl&#237;nica e as altera&#231;&#245;es eletrocardiogr&#225;ficas<sup>22</sup>. A MA est&#225; presente n&#227;o s&#243; na isquemia manifesta, mas tamb&#233;m na silenciosa<sup>23</sup>.</p>
    <p>Ainda em rela&#231;&#227;o &#224; DAC, a MA foi estudada em pacientes sem diabete e com hist&#243;ria pr&#233;via de infarto do mioc&#225;rdio, e observou-se que ela estava presente em 11% desses pacientes. A EAU tamb&#233;m esteve associada com aumento da espessura do complexo &#237;ntimo-m&#233;dia na art&#233;ria braquial e carot&#237;dea<sup>24</sup>.</p>
    <p>Quanto &#224; doen&#231;a arterial perif&#233;rica (DAOP), tamb&#233;m se observou rela&#231;&#227;o da MA com esta entidade. Pesquisadores espanh&#243;is estudaram 141 pacientes com s&#237;ndrome coronariana aguda, dividindo-os em dois grupos de acordo com a presen&#231;a ou aus&#234;ncia de DAOP e observaram que a MA era significativamente mais elevada no grupo com DAOP<sup>25</sup>. No ano seguinte, pesquisadores turcos estudaram popula&#231;&#227;o de 65 pacientes com DAOP que se submeteram a coronariografia e observaram que a EAU foi significativamente maior no grupo com DAC que no grupo sem DAC. Cumpre salientar que os autores utilizaram crit&#233;rio para diagn&#243;stico de DAC bastante abrangente: a presen&#231;a de estenose coronariana a partir de 25%<sup>26</sup>.</p>
    <p>Conclu&#237;mos ent&#227;o que: 1) a preval&#234;ncia de microalbumin&#250;ria em indiv&#237;duos hipertensos &#233; elevada, sendo ainda mais elevada em portadores de doen&#231;a coronariana; 2) existe correla&#231;&#227;o da presen&#231;a de microalbumin&#250;ria com idade, diabete e dislipidemia; 3) a microalbumin&#250;ria &#233; um forte preditor para a exist&#234;ncia de doen&#231;a coronariana.</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>A determina&#231;&#227;o da rela&#231;&#227;o da albumina/creatinina urin&#225;ria foi realizada com recursos do Laborat&#243;rio Sanofi.</p>
    <p>
      <bold>Vincula&#231;&#227;o Acad&#234;mica</bold>
    </p>
    <p>N&#227;o h&#225; vincula&#231;&#227;o acad&#234;mica deste estudo a programa de p&#243;s-gradua&#231;&#227;o.</p>
    <p>
      <fn id="end" fn-type="corresp">
        <label>
          <bold>Correspond&#234;ncia: </bold>
        </label>
        <p> Ricardo Pereira Silva </p>
        <p> Rua Rep&#250;blica do L&#237;bano, 630/1002 - Meireles </p>
        <p> 60160-140 - Fortaleza, CE - Brasil </p>
        <p> E-mail: </p>
        <p><email xlink:href="rpsilva@cardiol.br">rpsilva@cardiol.br</email>, </p>
        <p>
          <email xlink:href="ricardop@ufc.br">ricardop@ufc.br</email>
        </p>
      </fn>
    </p>
    <p>Artigo recebido em 07/05/07; revisado recebido em 22/06/07; aceito em 15/10/07.</p>
  </body>
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  <sub-article article-type="translation" id="TRen" xml:lang="en">
    <front-stub>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Original Articles</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title xml:lang="en">Determination of microalbuminuria in hypertensive patients and in patients with coronary artery disease</article-title>
      </title-group>
      <abstract xml:lang="en">
        <p>BACKGROUND: The normal 24-hour albumin excretion rate is of 20 mg. A persistent rate of 30 to 300 mg/day is called microalbuminuria and is related to a higher prevalence of cardiovascular disease. OBJECTIVE: 1) To determine the prevalence of microalbuminuria in a group of hypertensive patients and in a group of patients with coronary artery disease; 2) To determine the relationship between the presence of microalbuminuria and hypertension, diabetes mellitus, dyslipidemia, smoking and obesity. METHODS: The presence of microalbuminuria in a group of hypertensive patients (73 individuals) and in a group of patients with coronary artery disease (39 individuals) was determined and compared with a control group (43 individuals). Microalbuminuria was defined as an albumin/creatinine ratio higher than 30 and lower than 300 in a spot morning urine sample. The chi-square test and the Fisher&#8217;s exact test were used in the statistical analysis. RESULTS: Microalbuminuria was present in 9.5% of the hypertensive individuals and in 33% of the patients with coronary artery disease, and was absent in individuals of the control group. When the occurrence of microalbuminuria was analyzed according to the different clinical parameters, regardless of the group involved, a statistically significant correlation was found with age, diabetes and dyslipidemia. CONCLUSION: 1) The prevalence of microalbuminuria in hypertensive individuals is high, and is even higher in patients with coronary artery disease; 2) There is a correlation of the presence of microalbuminuria with age, diabetes and dyslipidemia.</p>
      </abstract>
      <kwd-group xml:lang="en">
        <kwd>Albuminuria</kwd>
        <kwd>hypertension</kwd>
        <kwd>coronary disease</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <p>
        <bold>ORIGINAL ARTICLE</bold>
      </p>
      <p><undefined id="tx-body2"/>Determination of microalbuminuria in hypertensive patients and in patients with coronary artery disease</p>
      <p>
        <bold>Ricardo Pereira Silva; Karinne Cisne; Jerusa Mara de Oliveira; Marcos Kubrusly; Carlos Roberto Martins Rodrigues Sobrinho; Pedro Jos&#233; Negreiros de Andrade</bold>
      </p>
      <p> Hospital Universit&#225;rio Walter Cant&#237;dio, Fortaleza, CE - Brazil</p>
      <p>Mailing Address</p>
      <p>
        <bold>SUMMARY</bold>
      </p>
      <p><bold>BACKGROUND:</bold> The normal 24-hour albumin excretion rate is of 20 mg. A persistent rate of 30 to 300 mg/day is called microalbuminuria and is related to a higher prevalence of cardiovascular disease.</p>
      <p><bold>OBJECTIVE: </bold>1) To determine the prevalence of microalbuminuria in a group of hypertensive patients and in a group of patients with coronary artery disease; 2) To determine the relationship between the presence of microalbuminuria and hypertension, diabetes mellitus, dyslipidemia, smoking and obesity.</p>
      <p><bold>METHODS:</bold> The presence of microalbuminuria in a group of hypertensive patients (73 individuals) and in a group of patients with coronary artery disease (39 individuals) was determined and compared with a control group (43 individuals). Microalbuminuria was defined as an albumin/creatinine ratio higher than 30 and lower than 300 in a spot morning urine sample. The chi-square test and the Fisher&#146;s exact test were used in the statistical analysis.</p>
      <p><bold>RESULTS:</bold> Microalbuminuria was present in 9.5% of the hypertensive individuals and in 33% of the patients with coronary artery disease, and was absent in individuals of the control group. When the occurrence of microalbuminuria was analyzed according to the different clinical parameters, regardless of the group involved, a statistically significant correlation was found with age, diabetes and dyslipidemia.</p>
      <p><bold>CONCLUSION: </bold>1) The prevalence of microalbuminuria in hypertensive individuals is high, and is even higher in patients with coronary artery disease; 2) There is a correlation of the presence of microalbuminuria with age, diabetes and dyslipidemia. (Arq Bras Cardiol 2008; 90(2):99-103)</p>
      <p><bold>Key words: </bold>Albuminuria/complications; hypertension; coronary disease.</p>
      <p>
        <bold>Introduction</bold>
      </p>
      <p>The normal 24-hour albumin excretion rate is of 20 mg. A persistent rate of 30 to 300 mg/day is called microalbuminuria. </p>
      <p>Twenty-four-hour urine collection is the standard method for the detection of microalbuminuria, although it can also be detected with the collection of the first morning void<sup>1-2</sup>.</p>
      <p>The volume effect can be avoided using the calculation of the albumin/creatinine ratio in a urine sample<sup>3</sup>.</p>
      <p>The three major limitations for the determination of microalbuminuria are: 1) Strenuous exercise, which may lead to a transient increase in albumin excretion<sup>4</sup>; 2) Alteration during the day in the relation between the collection of a spot urine sample and the 24-hour collection: there is a better correlation if the samples are obtained in the middle of the morning<sup>5</sup>; 3) The accuracy of the albumin/creatinine ratio decreases if creatinine excretion is very different from the estimated value, as occurs in men with high muscle mass or in cachectic individuals<sup>6</sup>.</p>
      <p>Preliminary studies demonstrated that microalbuminuria represented the earliest clinical manifestation of diabetic nephropathy, and its determination is now recommended for the initial assessment and follow-up of diabetic patients. </p>
      <p>Further studies demonstrated an association between microalbuminuria and cardiovascular disease in both diabetic and non-diabetic patients. </p>
      <p>The HOPE study showed that the presence of microalbuminuria was associated with an increased relative risk of primary endpoints (myocardial infarction, stroke or cardiovascular death). The risk of an adverse cardiovascular event increased progressively with the increase in the levels of microalbuminuria<sup>7</sup>.</p>
      <p>Further analysis of the LIFE study on hypertensive patients with electrocardiographic evidence of left ventricular hypertrophy showed that for every increase of 10 times in the albumin/creatinine ratio, the risk of infarction or stroke increased by 57%, and the risk of cardiovascular death by 98% for non-diabetic patients. Increases in diabetic patients were of 39% and 47%, respectively<sup>8</sup>.</p>
      <p>An analysis of the PREVEND study showed an increase in the relative risk of cardiovascular mortality of 1.35 for every two-fold increase in the value of albuminuria<sup>9</sup>.</p>
      <p>In elderly individuals, the combination of microalbuminuria and hyperinsulinemia, a reflex of insulin resistance, is associated with increased risk of coronary events and mortality<sup>10</sup>.</p>
      <p>Even very low levels of microalbuminuria may be associated with increased cardiovascular risk, as was demonstrated in the "Copenhagen City Heart Study". Patients with albuminuria greater than 6.9 mg/day had a relative risk of death of 1.9, and risk of coronary artery disease of 2.0<sup>11</sup>.</p>
      <p>The mechanism explaining the association between microalbuminuria and cardiovascular disease remains unknown. Microalbuminuria in non-diabetic individuals seems to be a sign from the kidneys that the vasculature, mainly the endothelium, is not functioning properly. This fact may be confirmed by the following evidences: 1) Vasodilation in response to some stimuli is reduced in normal elderly individuals with microalbuminuria when compared with those without albuminuria<sup>12</sup>. 2) Among non-diabetic hypertensive individuals, those with microalbuminuria show higher levels of von Willebrand factor than those without microalbuminuria. Since von Willebrand factor has been associated with occlusive thrombosis, elevations of this factor may contribute to an increase in cardiovascular disease<sup>13</sup>.</p>
      <p>Among non-diabetic hypertensive individuals, microalbuminuria is associated with higher pressure levels, higher cholesterol levels, and lower HDL levels<sup>14</sup>.</p>
      <p>The objectives of this study are: 1) To determine the prevalence of microalbuminuria in a group of hypertensive patients and in a group of patients with coronary artery disease; 2) To determine the relationship of the presence of microalbuminuria with hypertension, diabetes mellitus, dyslipidemia, smoking and obesity.</p>
      <p>
        <bold>Materials and methods</bold>
      </p>
      <p>Patients</p>
      <p><italic>Inclusion criteria - </italic>hypertensive patients with coronary artery disease treated at <italic>Hospital Universit&#225;rio Walter Cant&#237;dio. </italic>Healthy employees of the same hospital comprised the control group. </p>
      <p>Individuals with three or more blood pressure measurements equal to or higher than 140/90 mmHg or those with previous diagnosis of hypertension who were receiving antihypertensive drugs were considered hypertensive. Individuals with at least two fasting plasma glucose levels higher than 125 mg/dL or those being treated for diabetes with oral hypoglycemic agents and/or insulin were considered diabetic. Patients with cholesterol levels higher than 200 mg/dL or triglyceride levels higher than 150 mg/dL or who were receiving lipid-lowering drugs were considered dyslipidemic. Individuals who had smoked any amount of cigarettes in the past year were considered smokers. </p>
      <p>Patients with angiographically confirmed severe lesion (stenosis &gt; 70%) in at least one coronary artery were include in the group of coronary artery disease. </p>
      <p><italic>Exclusion criteria -</italic> patients with creatinine levels higher than 2 mg/dL were excluded from the study. </p>
      <p>
        <bold>Methods</bold>
      </p>
      <p>After weight and height were measured, the body mass index (BMI) was calculated using the formula: BMI = Weight/height<sup>2</sup>. Individuals with a BMI equal to or higher than 25 were considered overweight, and those with a BMI equal to or higher than 30 were considered obese. </p>
      <p>Waist circumference was measured and considered increased when higher than 80 cm for women or higher than 90 cm for men.</p>
      <p>An albumin/creatinine ratio higher than 30 in a spot morning urine sample was considered microalbuminuria. </p>
      <p>
        <bold>Statistical analysis</bold>
      </p>
      <p>The comparison of the H (hypertension) group and CAD (coronary artery disease) group with the control group regarding the different clinical parameters was performed using the chi-square test and the Fisher&#146;s exact test.</p>
      <p>In order to determine whether the incidence of MA (microalbuminuria) among CAD patients was different from that among H patients and individuals of the control group, the analysis of proportions with a sample proportion test (binomial) was used.</p>
      <p>To measure the presumed importance of microalbuminuria, BMI, waist circumference, smoking, dyslipidemia, diabetes mellitus and hypertension as determinant factors of coronary artery disease, the three original groups (CAD, H and control) were clustered so as to serve as a basis for a multivariate logistic analysis. In order to make that possible, the patients of each group received the auxiliary variables necessary to mark their original enrollment. Considering coronary artery disease as a dependent variable and all the other variables previously mentioned as independent variables, we started to seek the most appropriate model. We started from a model including all independent variables and used conventional techniques to include and eliminate variables.</p>
      <p>P values &lt; 0.05 were considered statistically significant. </p>
      <p>
        <bold>Results</bold>
      </p>
      <p>The group of hypertensive patients was comprised of 73 individuals, 23% of whom were males; the group of coronary patients included 39 individuals (43% males), and the control group was comprised of 43 individuals (9% males).</p>
      <p>When the group of hypertensive patients was compared to the control group, we observed that the hypertensive individuals were older, more obese, had a higher proportion of diabetic and dyslipidemic individuals, and of individuals with microalbuminuria. When the group of patients with coronary artery disease was compared to the control group, we observed that coronary patients were more frequently males, were older, and had a higher proportion of diabetic and dyslipidemic individuals and of individuals with microalbuminuria. Microalbuminuria was present in 9.5% of the hypertensive individuals, and in 33% of the patients with coronary artery disease, and was absent in individuals of the control group (<xref ref-type="table" rid="tab01-body2">Table 1</xref> and <xref ref-type="fig" rid="fig01-body2">Figure 1</xref>). Also as regards microalbuminuria, a statistically significant difference was found when the CAD group was compared to the control group (p&lt;0.001), when the H group was compared to the control group (p&lt; 0.001), and when the CAD group was compared to the H group (p&lt;0.001).</p>
      <table-wrap id="tab01-body2">
        <graphic xlink:href="1678-4170-abc-90-02-0108-00006-gt01-en.jpg"/></table-wrap>
      <fig id="fig01-body2">
        <graphic xlink:href="1678-4170-abc-90-02-0108-00006-gf01-en.jpg"/></fig>
      <p>When the occurrence of microalbuminuria was analyzed according to the different clinical parameters, regardless of the group considered, a statistically significant correlation was found with age, diabetes and dyslipidemia (<xref ref-type="table" rid="tab02-body2">Table 2</xref>). When we analyzed microalbuminuria in relation to the individuals&#146; weight, we found that microalbuminuria was absent in all the 37 obese individuals, but was present in 13 of the 67 overweight individuals (19.4%), and in 7 of the 39 individuals with normal weight (17.9%). When obese individuals were grouped with overweight individuals, we found a prevalence of only 13%, which is lower than that of individuals with normal weight.</p>
      <table-wrap id="tab02-body2">
        <graphic xlink:href="1678-4170-abc-90-02-0108-00006-gt02-en.jpg"/></table-wrap>
      <p>When the importance of microalbuminuria, BMI, waist circumference, smoking, dyslipidemia, diabetes mellitus, and hypertension was tested as determinant factors of the occurrence of coronary artery disease, we observed that diabetes mellitus, dyslipidemia, and microalbuminuria were determinant factors. Patients with microalbuminuria have a 4.5-fold higher chance of having coronary artery disease when compared to those without microalbuminuria. Diabetic patients and patients with dyslipidemia have a 4.3 and 4.1-fold higher chance, respectively.</p>
      <p>
        <bold>Discussion</bold>
      </p>
      <p>Microalbuminuria is known to be a risk factor for cardiovascular disease; however, it is not known whether this association results from an effect of microalbuminuria in the development of subclinical atherosclerosis or whether microalbuminuria destabilizes subclinical atherosclerosis, thus leading to clinical events. Cao et al<sup>15</sup> evaluated a population of 3312 participants in the "Cardiovascular Health Study" as regards MA. The participants were divided into three groups: individuals without diabetes or hypertension (33%), individuals with hypertension (52%), and diabetic individuals with or without hypertension (15%). For each one of the three groups, the relative risk of cardiovascular disease in the presence of MA increased by 1.7 to 1.8 times. However, MA was not associated with risk of subclinical atherosclerosis in the absence of hypertension or DM, which makes us believe that the mechanism of association of MA with cardiovascular disease involves destabilization of the vascular system, thus leading to clinically overt disease<sup>15</sup>.</p>
      <p>According to Cirillo, the main correlate with microalbuminuria is blood pressure, whether systolic or diastolic. The relationship between blood pressure and microalbuminuria is continuous and gradual because the prevalence of microalbuminuria increases with the severity of hypertension. For hypercholesterolemia, smoking and diabetes, data are less incisive, but they point to a positive independent association with microalbuminuria<sup>16</sup>. </p>
      <p>The prevalence of microalbuminuria in hypertensive individuals in our study was 9.5%, a value slightly lower than that found by other authors<sup>17</sup>.</p>
      <p>The prevalence of microalbuminuria among our obese or overweight patients was of only 13%, thus lower than that of the patients with normal weight (17.9%). Valensi et al<sup>18</sup> found prevalences of up to 12% of microalbuminuria among obese individuals. When hypertension was associated with obesity, the prevalence reached up to 19%<sup>18</sup>. In another study with obese or overweight individuals, central fat distribution implied an 18-fold higher risk of microalbuminuria in relation to lean individual, whereas among obese individuals with peripheral fat distribution, the risk was 4-fold higher<sup>19</sup>. A Brazilian study demonstrated a trend to borderline levels of nocturnal microalbuminuria, which was higher in normotensive obese females with central fat distribution<sup>20</sup>.</p>
      <p>A high prevalence of microalbuminuria was found among our patients with coronary artery disease (33%). Since the past decade, the association between microalbuminuria and coronary artery disease has been demonstrated, when Tuttle et al<sup>21</sup> studied 308 patients undergoing coronary angiography, previously determining the albumin/creatinine ratio in a spot morning urine sample. Urinary albumin excretion (UAE) in patients with CAD was significantly higher than in patients without CAD. Albumin excretion increased progressively with the severity of CAD. In patients without DM, a relationship between UAE and CAD was observed, but it was more significant in diabetic patients. In multiple regression analysis, the relative risk for severe CAD was 2.2 for MA (Am. J. Kidney Disease)<sup>21</sup>.</p>
      <p>The relationship between MA and CAD seems to be influenced by ethnicity. Tillin et al<sup>22</sup> studied a population from the city of London comprised of 1460 Europeans, 946 Asians, and 559 African-Caribbean and observed an association of MA with prevalence and mortality of CAD only for Asian males and European females. It should be noted that, in this study, the diagnostic criterion for CAD is highly debatable, because it includes only the clinical history and electrocardiographic changes<sup>22</sup>. MA is present not only in overt ischemia, but also in silent ischemia<sup>23</sup>.</p>
      <p>Also in relation to CAD, MA was studied in non-diabetic patients with a previous history of myocardial infarction and was found in 11% of these patients. UAE was also associated with increased thickness of the intima-media complex in the brachial and carotid arteries<sup>24</sup>.</p>
      <p>As regards peripheral arterial disease (PAD), a relationship between MA and this disease was also observed. Spanish researchers studied 141 patients with acute coronary syndrome and divided them into two groups according to the presence or absence of PAD, and observed that MA was significantly higher in the PAD group<sup>25</sup>. In the following year, Turkish researchers studied a population of 65 patients with PAD undergoing coronary angiography and observed that UAE was significantly higher in the group with CAD than in the group without CAD. We should point out that the authors used excessively encompassing diagnostic criteria for the diagnosis of CAD, such as the presence of coronary stenosis equal to or higher than 25%<sup>26</sup>.</p>
      <p>In conclusion: 1) The prevalence of microalbuminuria in hypertensive individuals is high, and is even higher in patients with coronary artery disease; 2) There is a correlation between the presence of microalbuminuria and age, diabetes and dyslipidemias; 3) Microalbuminuria is a strong predictor of the occurrence of coronary artery disease.</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>Determination of the relation of urinary albumin/creatinin was done with funds granted by <italic>Laborat&#243;rio Sanofi</italic>.</p>
      <p>
        <bold>Study Association</bold>
      </p>
      <p>This study is not associated with any graduation program.</p>
      <p>
        <bold>References</bold>
      </p>
    </body>
  </sub-article>
</article>
