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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">XGHNzWG5LVYNyWNZh3hVPYJ</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v2">S0066-782X2013003200003</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v1">S0066-782X(13)10100600003</article-id>
      <article-id pub-id-type="doi">10.5935/abc.20130221</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Artigos Originais</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Preval&#234;ncia de isquemia mioc&#225;rdica na cintilografia em mulheres nos per&#237;odos pr&#233;/p&#243;s-menopausa</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Santos</surname>
            <given-names>Daniel Augusto Message dos</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Navarro</surname>
            <given-names>Wendy Yasdin Sierraalta</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Alexandre</surname>
            <given-names>Leonardo Machado</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Cestari</surname>
            <given-names>Priscila Feitosa</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Smanio</surname>
            <given-names>Paola Emanuela Poggio</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">Instituto Dante Pazzanese de Cardiologia</institution>
        <country country="BR">Brazil</country>
      </aff>
      <pub-date date-type="collection" publication-format="electronic">
        <month>12</month>
        <year>2013</year>
      </pub-date>
      <volume>101</volume>
      <issue>6</issue>
      <fpage>487</fpage>
      <lpage>494</lpage>
      <history>
        <date date-type="received">
          <day>26</day>
          <month>02</month>
          <year>2013</year>
        </date>
        <date date-type="accepted">
          <day>28</day>
          <month>06</month>
          <year>2013</year>
        </date>
        <date date-type="rev-recd">
          <day>27</day>
          <month>06</month>
          <year>2013</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: No per&#237;odo p&#243;s-menopausa, a presen&#231;a dos fatores de risco para doen&#231;a arterial coron&#225;ria (DAC) aumentam. Entretanto, n&#227;o &#233; bem estabelecida a diferen&#231;a de preval&#234;ncia de isquemia mioc&#225;rdica em mulheres pr&#233;/p&#243;s-menopausa com m&#250;ltiplos fatores de risco para DAC. OBJETIVO: Comparar a preval&#234;ncia de isquemia na cintilografia de perfus&#227;o mioc&#225;rdica com sestamibi-99mTc (CPM) em mulheres nos per&#237;odos pr&#233;/p&#243;s-menopausa e avaliar se a menopausa pode ser considerada fator preditor de risco independente para isquemia em mulheres com m&#250;ltiplos fatores de risco para DAC. M&#201;TODOS: Analisamos, retrospectivamente, 500 CPM de mulheres pr&#233;/p&#243;s-menopausa, com m&#250;ltiplos fatores de risco cardiovascular. A an&#225;lise estat&#237;stica foi realizada por teste exato de Fisher e pelas an&#225;lises univariada e multivariada, sendo considerado significativo o valor de p &lt; 0,05. RESULTADOS: Do total, 55,9% das mulheres estavam no per&#237;odo p&#243;s-menopausa, 83,3% eram hipertensas, 28,9% diab&#233;ticas, 61,2% dislipid&#234;micas, 32,1% tabagistas, 25% obesas e 34,3% j&#225; apresentavam DAC conhecida. No grupo p&#243;s-menopausa, as mulheres eram mais hipertensas, diab&#233;ticas e dislipid&#234;micas, e tiveram menor capacidade funcional no teste ergom&#233;trico (p = &lt; 0,005). N&#227;o houve diferen&#231;a estat&#237;stica significativa na presen&#231;a de isquemia na CPM entre os grupos pr&#233;/p&#243;smenopausa (p = 0,395). A &#250;nica vari&#225;vel associada &#224; isquemia na CPM foi a presen&#231;a de DAC pr&#233;via (p = 0,004). CONCLUS&#195;O: Os resultados obtidos sugerem que, em mulheres com m&#250;ltiplos fatores de risco para DAC, a menopausa n&#227;o foi fator preditor independente de isquemia na CPM. Essas informa&#231;&#245;es refor&#231;am a ideia de que a investiga&#231;&#227;o de isquemia pela CPM em mulheres com m&#250;ltiplos fatores de risco para DAC talvez deva iniciar antes da menopausa.</p>
      </abstract>
      <kwd-group xml:lang="pt" kwd-group-type="author-generated">
        <kwd>Isquemia Mioc&#225;rdica</kwd>
        <kwd>Mulheres</kwd>
        <kwd>Pr&#233;-Menopausa</kwd>
        <kwd>P&#243;s-Menopausa</kwd>
        <kwd>Fatores de Risco</kwd>
      </kwd-group>
      <pub-date publication-format="electronic" date-type="pub">
        <day>12</day>
        <month>11</month>
        <year>2013</year>
      </pub-date>
    </article-meta>
  </front>
  <body><p><bold>Preval&#234;ncia de isquemia mioc&#225;rdica na cintilografia em mulheres nos per&#237;odos pr&#233;/p&#243;s-menopausa</bold></p><p><bold>Daniel Augusto Message dos Santos; Wendy Yasdin Sierraalta Navarro; Leonardo Machado Alexandre; Priscila Feitosa Cestari; Paola Emanuela Poggio Smanio</bold></p><p>Instituto Dante Pazzanese de Cardiologia, S&#227;o Paulo, SP - Brasil</p><p><xref ref-type="corresp" rid="end">Correspond&#234;ncia</xref></p><p><bold>RESUMO</bold></p><p><bold>FUNDAMENTO:</bold> No per&#237;odo p&#243;s-menopausa, a presen&#231;a dos fatores de risco para doen&#231;a arterial coron&#225;ria (DAC) aumentam. Entretanto, n&#227;o &#233; bem estabelecida a diferen&#231;a de preval&#234;ncia de isquemia mioc&#225;rdica em mulheres pr&#233;/p&#243;s-menopausa com m&#250;ltiplos fatores de risco para DAC. </p><p><bold>OBJETIVO:</bold> Comparar a preval&#234;ncia de isquemia na cintilografia de perfus&#227;o mioc&#225;rdica com sestamibi-<sup>99m</sup>Tc (CPM) em mulheres nos per&#237;odos pr&#233;/p&#243;s-menopausa e avaliar se a menopausa pode ser considerada fator preditor de risco independente para isquemia em mulheres com m&#250;ltiplos fatores de risco para DAC. </p><p><bold>M&#201;TODOS:</bold> Analisamos, retrospectivamente, 500 CPM de mulheres pr&#233;/p&#243;s-menopausa, com m&#250;ltiplos fatores de risco cardiovascular. A an&#225;lise estat&#237;stica foi realizada por teste exato de Fisher e pelas an&#225;lises univariada e multivariada, sendo considerado significativo o valor de p <underline>&lt;</underline> 0,05. </p><p><bold>RESULTADOS:</bold> Do total, 55,9% das mulheres estavam no per&#237;odo p&#243;s-menopausa, 83,3% eram hipertensas, 28,9% diab&#233;ticas, 61,2% dislipid&#234;micas, 32,1% tabagistas, 25% obesas e 34,3% j&#225; apresentavam DAC conhecida. No grupo p&#243;s-menopausa, as mulheres eram mais hipertensas, diab&#233;ticas e dislipid&#234;micas, e tiveram menor capacidade funcional no teste ergom&#233;trico (p = &lt; 0,005). N&#227;o houve diferen&#231;a estat&#237;stica significativa na presen&#231;a de isquemia na CPM entre os grupos pr&#233;/p&#243;smenopausa (p = 0,395). A &#250;nica vari&#225;vel associada &#224; isquemia na CPM foi a presen&#231;a de DAC pr&#233;via (p = 0,004). </p><p><bold>CONCLUS&#195;O:</bold> Os resultados obtidos sugerem que, em mulheres com m&#250;ltiplos fatores de risco para DAC, a menopausa n&#227;o foi fator preditor independente de isquemia na CPM. Essas informa&#231;&#245;es refor&#231;am a ideia de que a investiga&#231;&#227;o de isquemia pela CPM em mulheres com m&#250;ltiplos fatores de risco para DAC talvez deva iniciar antes da menopausa.</p><p><bold>Palavras-chave:</bold> Isquemia Mioc&#225;rdica/cintilografia; Mulheres; Pr&#233;-Menopausa; P&#243;s-Menopausa; Fatores de Risco.</p><p><bold>Introdu&#231;&#227;o</bold></p><p>Apenas mais recentemente, os principais estudos sobre doen&#231;a arterial coron&#225;ria (DAC) come&#231;aram a incluir as mulheres<sup>1-3</sup>.</p><p>As mulheres s&#227;o mais obesas e fumam mais que os homens; 25% das mulheres s&#227;o sedent&#225;rias, 52% acima de 45 anos s&#227;o portadoras de hipertens&#227;o arterial e 40% daquelas acima de 55 anos t&#234;m hipercolesterolemia<sup>1,2</sup>. As mulheres diab&#233;ticas t&#234;m alt&#237;ssimo risco cardiovascular, compar&#225;vel ao daquelas que j&#225; apresentaram infarto do mioc&#225;rdio, com mais desfechos adversos<sup>4,5</sup>.</p><p>As manifesta&#231;&#245;es cl&#237;nicas de DAC aparecem cerca de 10-15 anos mais tardiamente nas mulheres, fato relacionado &#224; poss&#237;vel prote&#231;&#227;o estrog&#234;nica. Com a melhora na expectativa de vida, elas passaram a viver um ter&#231;o da vida no per&#237;odo p&#243;s-menopausa, gerando maior interesse na avalia&#231;&#227;o dessa popula&#231;&#227;o espec&#237;fica<sup>1,2,6,7</sup>.</p><p>Alguns dos testes diagn&#243;sticos tradicionais para investiga&#231;&#227;o de DAC n&#227;o funcionam t&#227;o adequadamente no sexo feminino, e evid&#234;ncias sugerem maior valor progn&#243;stico do que diagn&#243;stico em mulheres<sup>8,9</sup>.</p><p>O teste ergom&#233;trico oferece informa&#231;&#245;es importantes, por&#233;m a sensibilidade e a especificidade m&#233;dia s&#227;o menores em rela&#231;&#227;o ao sexo masculino, em torno de 61% e 69%, respectivamente<sup>10</sup>. Al&#233;m disso, altera&#231;&#245;es inespec&#237;ficas eletrocardiogr&#225;ficas basais do segmento ST, decorrentes de a&#231;&#227;o hormonal estrog&#234;nica, podem gerar testes com resultados "falsamente" sugestivos de isquemia<sup>10</sup>.</p><p>A CPM se torna ferramenta de grande import&#226;ncia na investiga&#231;&#227;o diagn&#243;stica no sexo feminino, em particular nas mulheres com eletrocardiograma basal com altera&#231;&#245;es inespec&#237;ficas e tamb&#233;m com baixa capacidade funcional ou dificuldade para atingir a frequ&#234;ncia card&#237;aca adequada, o que &#233; muito comum no grupo de diab&#233;ticas e portadoras de doen&#231;a vascular perif&#233;rica<sup>11,12</sup>. Tamb&#233;m a diminui&#231;&#227;o de artefatos por atenua&#231;&#227;o mam&#225;ria e a aquisi&#231;&#227;o de imagens sincronizadas com o eletrocardiograma (<italic>gated-SPECT</italic>) ajudam a aumentar a acur&#225;cia do teste, auxiliando na diferencia&#231;&#227;o de reais defeitos e artefatos<sup>13</sup>.</p><p>Em rela&#231;&#227;o &#224; prote&#231;&#227;o estrog&#234;nica quanto ao risco cardiovascular, estudos<sup>7,14</sup> pr&#233;vios documentaram que ela est&#225; associada &#224; diminui&#231;&#227;o do risco; entretanto, pouco h&#225; na literatura sobre o papel dos m&#233;todos diagn&#243;sticos n&#227;o invasivos, em especial a cintilografia de perfus&#227;o mioc&#225;rdica com sestamibi-<sup>99m</sup>Tc em mulheres no per&#237;odo pr&#233;/p&#243;s-menopausa, principalmente naquelas com m&#250;ltiplos fatores de risco para DAC.</p><p><bold>Objetivos</bold></p><p>Os objetivos do presente estudo s&#227;o comparar a presen&#231;a de isquemia na cintilografia de perfus&#227;o mioc&#225;rdica com sestamibi-<sup>99m</sup>Tc em mulheres de alto risco para DAC, nos per&#237;odos pr&#233;/p&#243;s-menopausa, e tamb&#233;m analisar se a menopausa &#233; fator preditor independente de isquemia nesse grupo de pacientes.</p><p><bold>M&#233;todos</bold></p><p>Estudo observacional, retrospectivo, realizado no setor de medicina nuclear do Instituto Dante Pazzanese de Cardiologia, com revis&#227;o de prontu&#225;rios, analisou 500 cintilografias de perfus&#227;o mioc&#225;rdica em mulheres consecutivas que realizaram o exame em 2011 e 2012. O n&#250;mero de aprova&#231;&#227;o pelo comit&#234; de pesquisa e &#233;tica foi 02020312.7.0000.5462. Todas as pacientes assinaram termo de consentimento informado antes de realizar a cintilografia de perfus&#227;o mioc&#225;rdica.</p><p>As provas de estresse f&#237;sico e farmacol&#243;gico (com dipiridamol e dobutamina) e a aquisi&#231;&#227;o e o processamento das imagens de medicina nuclear foram realizados pelas t&#233;cnicas-padr&#227;o, conforme as diretrizes da Sociedade Brasileira de Cardiologia/Departamento de Ergometria, Exerc&#237;cio, Cardiologia Nuclear e Reabilita&#231;&#227;o Cardiovascular<sup>15,16</sup>.</p><p>A cintilografia mioc&#225;rdica foi realizada pela t&#233;cnica de <italic>gated-SPECT</italic>, protocolo de um dia, sendo a fase basal seguida pela fase de estresse. As imagens foram adquiridas em gamac&#226;mara cardiodedicada GE Ventri. Para a avalia&#231;&#227;o da perfus&#227;o mioc&#225;rdica, o mioc&#225;rdio foi dividido em 17 segmentos. Considerou-se perfus&#227;o normal na aus&#234;ncia de hipocapta&#231;&#227;o do radiof&#225;rmaco em ambas as fases (basal e estresse), sugestiva de isquemia e fibrose, na presen&#231;a de hipocapta&#231;&#227;o revers&#237;vel e fixa do radiof&#225;rmaco ap&#243;s a fase de estresse em rela&#231;&#227;o &#224; fase basal, ao menos em tr&#234;s dos 17 segmentos do mioc&#225;rdio analisados<sup>15</sup>.</p><p>A an&#225;lise visual qualitativa da presen&#231;a ou n&#227;o de altera&#231;&#245;es perfusionais foi realizada por dois observadores especialistas em cardiologia e em medicina nuclear, e, em caso de discord&#226;ncia entre os achados, era solicitado um terceiro observador, tamb&#233;m com as duas especialidades.</p><p>Para este estudo levamos em considera&#231;&#227;o a presen&#231;a de isquemia mioc&#225;rdica na cintilografia. Entretanto, apenas a t&#237;tulo de informa&#231;&#227;o, do total, 69 pacientes apresentavam altera&#231;&#227;o perfusional sugestiva de fibrose mioc&#225;rdica, das quais 41 encontravam-se no per&#237;odo p&#243;s-menopausa e 28 no per&#237;odo pr&#233;-menopausa (p = 0,069).</p><p>A divis&#227;o entre pacientes pr&#233;/p&#243;s-menopausa foi feita de acordo com a informa&#231;&#227;o em prontu&#225;rio m&#233;dico.</p><p>Os fatores de risco cardiovasculares cl&#225;ssicos analisados foram hipertens&#227;o arterial, diabetes melito, dislipidemia, tabagismo e obesidade, sendo definidos conforme diretriz da Sociedade Brasileira de Cardiologia<sup>17</sup>.</p><p>Foram considerados pacientes com DAC conhecida aquelas com diagn&#243;stico pr&#233;vio de infarto mioc&#225;rdico, angina inst&#225;vel/est&#225;vel e revasculariza&#231;&#227;o mioc&#225;rdica percut&#226;nea ou cir&#250;rgica. Al&#233;m disso, consideramos como equivalentes de alto risco cardiovascular pacientes com acidente vascular cerebral, doen&#231;a carot&#237;dea e de art&#233;rias perif&#233;ricas, aneurisma de aorta abdominal e insufici&#234;ncia renal cr&#244;nica<sup>17</sup>.</p><p>Foram exclu&#237;das as pacientes com cardiopatias n&#227;o isqu&#234;micas e as que n&#227;o tinham a informa&#231;&#227;o sobre menopausa relatada no prontu&#225;rio. </p><p>A an&#225;lise estat&#237;stica foi realizada pelo teste exato de Fisher e pelas an&#225;lises univariada e multivariada, sendo considerados significativos valores de p <underline>&lt;</underline> 0,05.</p><p><bold>Resultados</bold></p><p>Na <xref ref-type="table" rid="aop_5455tab01">Tabela 1</xref>, encontram-se as caracter&#237;sticas clinicoepidemiol&#243;gicas do grupo avaliado.</p><p content-type="asset"><table-wrap id="aop_5455tab01"><graphic xlink:href="1678-4170-abc-101-06-0487-30221-gt01.jpg"/></table-wrap></p><p>As cintilografias mioc&#225;rdicas foram realizadas por indica&#231;&#227;o cl&#237;nica dos m&#233;dicos dos setores ambulatoriais de onde as pacientes eram acompanhadas na institui&#231;&#227;o.</p><p>As indica&#231;&#245;es foram divididas em pacientes sintom&#225;ticas e assintom&#225;ticas, conforme as <xref ref-type="table" rid="aop_5455tab02">Tabelas 2</xref> e <xref ref-type="table" rid="aop_5455tab03">3</xref>. A <xref ref-type="table" rid="aop_5455tab04">Tabela 4</xref> divide o comportamento da CPM nas pacientes assintom&#225;ticas.</p><p content-type="asset"><table-wrap id="aop_5455tab02"><graphic xlink:href="1678-4170-abc-101-06-0487-30221-gt02.jpg"/></table-wrap></p><p content-type="asset"><table-wrap id="aop_5455tab03"><graphic xlink:href="1678-4170-abc-101-06-0487-30221-gt03.jpg"/></table-wrap></p><p content-type="asset"><table-wrap id="aop_5455tab04"><graphic xlink:href="1678-4170-abc-101-06-0487-30221-gt04.jpg"/></table-wrap></p><p>Em rela&#231;&#227;o aos exames estressores, as frequ&#234;ncias de teste ergom&#233;trico e est&#237;mulo com dipiridamol e dobutamina, assim como caracter&#237;sticas cl&#237;nicas, inclusive aptid&#227;o f&#237;sica ou capacidade funcional, s&#227;o mostradas nas <xref ref-type="table" rid="aop_5455tab05_07">Tabelas 5 a 7</xref>.</p><p><table-wrap id="aop_5455tab05_07"/>&#13;
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&#160;&#13;
<p><table-wrap id="aop_5455tab06"><graphic xlink:href="1678-4170-abc-101-06-0487-30221-gt06.jpg"/></table-wrap></p>&#13;
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<p><table-wrap id="aop_5455tab07"><graphic xlink:href="1678-4170-abc-101-06-0487-30221-gt07.jpg"/></table-wrap></p>&#13;
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&#13;
 <p>O grau de aptid&#227;o f&#237;sica, mais conhecido como capacidade funcional, medido em equivalentes metab&#243;licos (MET) pelo teste ergom&#233;trico se mostrou significativamente menor em mulheres na p&#243;s-menopausa. Do total, 91 das pacientes tinham 10 MET ou menos, 56 na p&#243;s-menopausa e 35 na pr&#233;-menopausa, com p &lt; 0,005, tinham capacidade funcional reduzida (&lt; 10 MET no teste ergom&#233;trico). A &#250;nica vari&#225;vel que se mostrou preditora de isquemia na cintilografia mioc&#225;rdica foi a presen&#231;a de DAC pr&#233;via (p &lt; 0,05). </p> <p>Quando comparada a presen&#231;a de isquemia na CPM nas 500 pacientes, 102 (58,5%) eram p&#243;s-menopausa e 72 (41,5%) eram pr&#233;-menopausa, sem signific&#226;ncia estat&#237;stica, com p = 0,395.</p> <p>A <xref ref-type="fig" rid="aop_5455fig01">Figura 1</xref> ilustra o exemplo de uma paciente do estudo, de 46 anos, diab&#233;tica, hipertensa, obesa, dislipid&#234;mica, sedent&#225;ria, com DAC conhecida (stent na art&#233;ria descendente anterior h&#225; tr&#234;s anos), que realizou cintilografia sob est&#237;mulo farmacol&#243;gico com dipiridamol, sendo a prova funcional sugestiva de isquemia por infradesnivelamento do segmento ST durante a infus&#227;o de dipiridamol e na cintilografia por hipocapta&#231;&#227;o transit&#243;ria do radiof&#225;rmaco nas paredes anterior, anterosseptal e apical.</p><p content-type="asset"><fig id="aop_5455fig01"><graphic xlink:href="1678-4170-abc-101-06-0487-30221-gf01.jpg"/></fig></p>   <p><bold>Discuss&#227;o</bold></p> <p>O diagn&#243;stico de doen&#231;a arterial coron&#225;ria apresenta um grande desafio no sexo feminino. Como os sintomas de DAC s&#227;o menos t&#237;picos em mulheres, &#233; inquestion&#225;vel o valor das provas n&#227;o invasivas para a investiga&#231;&#227;o efetiva antes de submet&#234;-las a exames invasivos, algumas vezes desnecess&#225;rios. No estudo <italic>Coronary Artery Surgery</italic> (CASS), metade das mulheres submetidas &#224; cinecoronariografia n&#227;o apresentava les&#245;es significativas<sup>17</sup>.</p> <p>Por ser hospital terci&#225;rio cardiol&#243;gico, em geral, as mulheres acompanhadas em nossa institui&#231;&#227;o apresentam m&#250;ltiplos fatores de risco para DAC e, em sua grande maioria, j&#225; apresentaram infarto do mioc&#225;rdio pr&#233;vio e/ou procedimentos de revasculariza&#231;&#227;o mioc&#225;rdica (como visto neste estudo, 34% com DAC pr&#233;via conhecida). Por esse motivo, decidimos realizar estudo que refletisse a realidade do grupo feminino encaminhado para a cintilografia mioc&#225;rdica, n&#227;o sendo exclu&#237;das aquelas portadoras de DAC pr&#233;via. </p> <p>Tivemos como objetivo verificar se a menopausa era preditora independente de isquemia nas mulheres de nossa institui&#231;&#227;o, com e sem DAC conhecida. </p> <p>Vale ainda salientar que muitas mulheres de nosso estudo apresentavam altera&#231;&#245;es eletrocardiogr&#225;ficas pr&#233;vias em ECG basal e baixa capacidade funcional, o que motivou o encaminhamento para a cintilografia mioc&#225;rdica, para investiga&#231;&#227;o diagn&#243;stica e estratifica&#231;&#227;o de risco cardiovascular.</p> <p>Como afirmado, a escolha e a interpreta&#231;&#227;o dos procedimentos n&#227;o invasivos tamb&#233;m n&#227;o s&#227;o tarefas f&#225;ceis. Sabe-se que o teste ergom&#233;trico tem menor sensibilidade e especificidade, em compara&#231;&#227;o ao sexo masculino<sup>18</sup>. A sensibilidade e a especificidade do teste farmacol&#243;gico ou de exerc&#237;cio podem ser refor&#231;adas por m&#233;todos de imagem que melhoram a acur&#225;cia diagn&#243;stica<sup>10,11,18</sup>. Com a evolu&#231;&#227;o da t&#233;cnica observou-se diminui&#231;&#227;o dos artefatos de atenua&#231;&#227;o (mam&#225;ria, por exemplo), levando a maior especificidade<sup>13</sup>.</p> <p>No presente estudo, a cintilografia mioc&#225;rdica mostrou-se ferramenta importante na investiga&#231;&#227;o de isquemia. Como pode ser observado, 35% das mulheres apresentavam isquemia. Esses dados tamb&#233;m s&#227;o observados na literatura. Smanio e cols.<sup>11</sup> encontraram, em 104 mulheres diab&#233;ticas assintom&#225;ticas, 34 (32,7%) com isquemia mioc&#225;rdica na cintilografia.</p> <p>A cintilografia mioc&#225;rdica tem seu papel estabelecido no diagn&#243;stico de DAC e na estratifica&#231;&#227;o de risco cardiovascular em ambos os g&#234;neros. Com essa t&#233;cnica pode-se obter informa&#231;&#245;es da perfus&#227;o mioc&#225;rdica, da fun&#231;&#227;o ventricular esquerda e, ainda, se necess&#225;rio, informa&#231;&#245;es sobre a presen&#231;a de viabilidade mioc&#225;rdica. Sua adi&#231;&#227;o ao teste ergom&#233;trico, em particular no sexo feminino, promove importante incremento na acur&#225;cia diagn&#243;stica<sup>7,19</sup>.</p> <p>Mieres e cols.<sup>20 </sup>avaliaram 46 mulheres no per&#237;odo p&#243;s-menopausa com teste ergom&#233;trico e cintilografia mioc&#225;rdica, sendo os valores encontrados de sensibilidade e especificidade, respectivamente, de 67% e 69% para o teste ergom&#233;trico e, na cintilografia, de 88% e 87,5% (p &lt; 0,0001). </p> <p>J&#225; &#233; conhecida tamb&#233;m a import&#226;ncia progn&#243;stica da cintilografia no sexo feminino<sup>9,21</sup>. H&#225; um grande corpo de evid&#234;ncias relativas &#224; CM com estresse, mostrando que efetivamente estratifica o risco nas mulheres com suspeita de DAC. Em mulheres com estudo de perfus&#227;o mioc&#225;rdica normal, a taxa de evento anual &#233; muito baixa (0,6% ao ano), em contraste com uma taxa de eventos muito maior (5% ao ano) em mulheres com perfus&#227;o do mioc&#225;rdio anormal<sup>22</sup>.</p> <p>Atribui-se o menor risco cardiovascular na fase pr&#233;-menopausa &#224; prote&#231;&#227;o dada pelos n&#237;veis de estrog&#234;nio plasm&#225;tico<sup>23,24</sup>. Este promove vasodilata&#231;&#227;o arterial atrav&#233;s do aumento da s&#237;ntese de &#243;xido n&#237;trico pelas c&#233;lulas endoteliais, aumenta as part&#237;culas de HDL-colesterol e diminui as de LDL-colesterol, al&#233;m de diminuir os n&#237;veis s&#233;ricos de fibrinog&#234;nio, antitrombina e prote&#237;na S<sup>24</sup>.</p> <p>A hipoestrogenemia apresentada na fase p&#243;s-menopausa leva &#224; disfun&#231;&#227;o endotelial microvascular e &#224; consequente progress&#227;o da placa ateroscler&#243;tica<sup>23,24</sup>. Diferentemente dos efeitos end&#243;genos, a terapia com horm&#244;nios ex&#243;genos mostrou aumento dos riscos de doen&#231;a cardiovascular<sup>23-26</sup>.</p> <p>O estudo WHI (<italic>Women's Health Initiative</italic>) mostrou, em 2002, que o benef&#237;cio da terapia de reposi&#231;&#227;o hormonal (TRH) se limitava a um pequeno grupo de mulheres na chamada "janela de oportunidade", no in&#237;cio da menopausa (entre 50-59 anos), quando associada &#224; aus&#234;ncia de fatores de risco cardiovascular. Estudos mais novos confirmaram essas informa&#231;&#245;es<sup>27</sup>. Entretanto, publica&#231;&#227;o recente da <italic>American Heart Association</italic> (AHA) contraindica o uso de TRH como preven&#231;&#227;o prim&#225;ria e secund&#225;ria de doen&#231;as cardiovasculares<sup>28</sup>.</p> <p>Leuzzi e cols.<sup>29</sup> relatam, em interessante editorial, que, apesar da maior preval&#234;ncia de DAC ap&#243;s a menopausa, mais estudos s&#227;o necess&#225;rios para podermos dizer se a menopausa &#233; um fator de risco cardiovascular.</p> <p>Essa associa&#231;&#227;o entre a entrada na menopausa e a presen&#231;a de DAC talvez possa ser observada em mulheres de baixo risco, mas naquelas com m&#250;ltiplos fatores de risco, como diabetes, hipertens&#227;o, dislipidemia, obesidade, sedentarismo, como observado em nosso estudo, a menopausa talvez n&#227;o seja fator preditor de isquemia. Os mesmos achados foram observados por Sood e cols.<sup>14 </sup>avaliando 2.194 mulheres antes e ap&#243;s a menopausa, com risco intermedi&#225;rio para DAC pelo escore de Duke no teste ergom&#233;trico e pela CM. Nesse estudo, a menopausa n&#227;o se mostrou preditora de eventos cardiovasculares, e a cintilografia mostrou-se bem superior ao escore de Duke na avalia&#231;&#227;o progn&#243;stica. Estudo com maior n&#250;mero de pacientes deve ser realizado para que tal afirma&#231;&#227;o possa verdadeiramente ser comprovada.</p>   <p><bold>Conclus&#227;o</bold></p> <p>Os resultados obtidos sugerem que, em mulheres com m&#250;ltiplos fatores de risco para DAC, a menopausa n&#227;o foi fator preditor independente de isquemia na cintilografia de perfus&#227;o mioc&#225;rdica com sestamibi-<sup>99m</sup>Tc. O &#250;nico fator que se mostrou preditor nesse grupo foi a presen&#231;a de DAC conhecida. Essas informa&#231;&#245;es refor&#231;am a ideia de que a investiga&#231;&#227;o de isquemia pela cintilografia em mulheres com m&#250;ltiplos fatores de risco para DAC talvez deva iniciar antes da menopausa.</p>   <p><bold>Contribui&#231;&#227;o dos autores</bold></p> <p>Concep&#231;&#227;o e desenho da pesquisa, Obten&#231;&#227;o de dados, An&#225;lise e interpreta&#231;&#227;o dos dados, An&#225;lise estat&#237;stica, Reda&#231;&#227;o do manuscrito, Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do intelectual: Santos DAM, Sierraalta WY, Alexandre LM, Smanio PEP, Cestari PF.</p> <p><bold>Potencial Conflito de Interesses</bold></p> <p>Declaro n&#227;o haver conflito de interesses pertinentes.</p> <p><bold>Fonte de Financiamento</bold></p> <p>O presente estudo n&#227;o teve fontes de financiamento externas.</p> <p><bold>Vincula&#231;&#227;o Acad&#234;mica</bold></p> <p>Este artigo &#233; parte de tese de conclus&#227;o de especializa&#231;&#227;o em cardiologia de Daniel Augusto Massage dos Santos e Wendy Yasdin Sierraalta pelo Instituto Dante Pazzanese.</p>                                    <p><fn id="end" fn-type="corresp"><label><bold>Correspond&#234;ncia:</bold></label><p> Daniel Augusto Message dos Santos </p><p> Rua do Grito, 479, apt.&#186; 62 Life, Ipiranga </p><p> CEP 04217-000, S&#227;o Paulo, SP - Brasil </p><p> E-mail: </p><p><email xlink:href="danielmessage@cardiol.br">danielmessage@cardiol.br</email>, </p><p><email xlink:href="daniel_message26@yahoo.com.br">daniel_message26@yahoo.com.br</email></p></fn></p> <p>Artigo recebido em 26/02/13; revisado em 27/06/13; aceito em 28/06/13.</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">Prevalence of ischemia on myocardial perfusion scintigraphy of pre-and postmenopausal women</article-title>
      </title-group>
      <abstract xml:lang="en">
        <p>BACKGROUND: In postmenopausal women, the presence of risk factors for coronary artery disease (CAD) increases. However, the difference in prevalence of ischemia between pre- and postmenopausal women with multiple risk factors for CAD has not been well established. OBJECTIVES: To compare the prevalence of ischemia on Tc99m-sestamibi myocardial perfusion scintigraphy (MPS) in pre- and postmenopausal women, and to evaluate whether menopause can be considered an independent risk predictor of ischemia in women with multiple risk factors for CAD. METHODS: This study retrospectively assessed 500 MPS of pre- and postmenopausal women with multiple risk factors for CAD. Statistical analysis was performed by using Fisher exact test and univariate and multivariate analysis, a p value &lt; 0.05 being considered significant. RESULTS: Postmenopausal women represented 55.9% of the sample; 83.3% were hypertensive; 28.9%, diabetic; 32.1%, smokers; 25%, obese; 61.2% had high cholesterol levels; and 34.3% had known CAD. Postmenopausal women were more often hypertensive, diabetic and dyslipidemic, and had lower functional capacity on exercise testing (p = &lt; 0.005). The presence of ischemia on MPS did not significantly differ between the pre- and postmenopausal groups (p = 0.395). The only variable associated with ischemia on MPS was known CAD (p = 0.004). CONCLUSION: The results suggest that, in women with multiple risk factors for CAD, menopause was not an independent predictor of ischemia on MPS. Those data support the idea that the investigation of ischemia via MPS in women with multiple risk factors for CAD should begin prior to menopause.</p>
      </abstract>
      <kwd-group xml:lang="en">
        <kwd>Myocardial Ischemia</kwd>
        <kwd>Women</kwd>
        <kwd>Premenopause</kwd>
        <kwd>Posmenopause</kwd>
        <kwd>Risk factors</kwd>
      </kwd-group>
    </front-stub>
    <body><p><fn id="enda-body2"><label><bold>Prevalence of ischemia on myocardial perfusion scintigraphy of pre-and postmenopausal women</bold></label><p><bold>Daniel Augusto Message dos Santos; Wendy Yasdin Sierraalta Navarro; Leonardo Machado Alexandre; Priscila Feitosa Cestari; Paola Emanuela Poggio Smanio</bold></p></fn></p><p>Instituto Dante Pazzanese de Cardiologia, S&#227;o Paulo, SP - Brazil</p><p>Mailing Address</p><p><bold>ABSTRACT</bold></p><p><bold>BACKGROUND:</bold> In postmenopausal women, the presence of risk factors for coronary artery disease (CAD) increases. However, the difference in prevalence of ischemia between pre- and postmenopausal women with multiple risk factors for CAD has not been well established.</p><p><bold>OBJECTIVES:</bold> To compare the prevalence of ischemia on Tc<sup>99m</sup>-sestamibi myocardial perfusion scintigraphy (MPS) in pre- and postmenopausal women, and to evaluate whether menopause can be considered an independent risk predictor of ischemia in women with multiple risk factors for CAD.</p><p><bold>METHODS:</bold> This study retrospectively assessed 500 MPS of pre- and postmenopausal women with multiple risk factors for CAD. Statistical analysis was performed by using Fisher exact test and univariate and multivariate analysis, a p value <underline>&lt;</underline> 0.05 being considered significant.</p><p><bold>RESULTS:</bold> Postmenopausal women represented 55.9% of the sample; 83.3% were hypertensive; 28.9%, diabetic; 32.1%, smokers; 25%, obese; 61.2% had high cholesterol levels; and 34.3% had known CAD. Postmenopausal women were more often hypertensive, diabetic and dyslipidemic, and had lower functional capacity on exercise testing (p = &lt; 0.005). The presence of ischemia on MPS did not significantly differ between the pre- and postmenopausal groups (p = 0.395). The only variable associated with ischemia on MPS was known CAD (p = 0.004).</p><p><bold>CONCLUSION:</bold> The results suggest that, in women with multiple risk factors for CAD, menopause was not an independent predictor of ischemia on MPS. Those data support the idea that the investigation of ischemia via MPS in women with multiple risk factors for CAD should begin prior to menopause.</p><p><bold>Keywords:</bold> Myocardial Ischemia/radionuclide imaging; Women; Premenopause; Posmenopause; Risk factors.</p><p><bold>Introduction</bold></p><p>It was only recently that the major studies on coronary artery disease (CAD) began to include women<sup>1-3</sup>.</p><p>Women are usually more obese and smoke more than men; 25% of women have sedentary lifestyles, 52% of those over the age of 45 years have arterial hypertension and 40% of those over the age of 55 years have hypercholesterolemia<sup>1,2</sup>. Diabetic women are at an extremely high cardiovascular risk, comparable to that of women who already had myocardial infarction, with more adverse outcomes<sup>4,5</sup>.</p><p>The clinical manifestations of CAD appear approximately 10 to 15 years later in women, a fact possibly related to estrogen protection. With the increase in life expectancy, the postmenopausal period began to represent one third of a woman's life, drawing more attention to that specific population<sup>1,2,6,7</sup>.</p><p>Some of the traditional diagnostic tests for CAD investigation do not function so properly in the female sex, and evidence has suggested that they have a greater prognostic rather than diagnostic value for women<sup>8,9</sup>.</p><p>Exercise testing provides important information, but its mean sensitivity and specificity are lower than in the male sex, around 61% and 69%, respectively<sup>10</sup>. In addition, unspecific baseline electrocardiographic alterations of the ST segment, due to estrogenic hormone action, might generate tests whose results "falsely" suggest ischemia<sup>10</sup>.</p><p>Myocardial perfusion scintigraphy (MPS) has become a highly important tool for diagnostic investigation in the female sex, particularly in women with unspecific alterations on baseline electrocardiogram and with low functional capacity or difficulty to achieve the proper heart rate, which is very common in the group of diabetic women and those with peripheral vascular disease<sup>11,12</sup>. In addition, the reduction in breast attenuation artifacts and the acquisition of images guided by electrocardiography (gated-SPECT) increase the accuracy of the test, helping to differentiate real defects and artifacts<sup>13</sup>.</p><p>Previous studies<sup>7,14</sup> have reported that estrogenic protection is associated with a reduction in cardiovascular risk; however, there is scarce literature about the role of non-invasive diagnostic methods, especially Tc<sup>99m</sup>-sestamibi MPS in pre/postmenopausal women, mainly in those with multiple risk factors for CAD.</p><p><bold>Objectives</bold></p><p>The present study aimed at comparing the presence of ischemia on Tc<sup>99m</sup>-sestamibi MPS in pre/postmenopausal women at high risk for CAD, and at assessing whether menopause is an independent predictive factor of ischemia in that group of patients.</p><p><bold>Methods</bold></p><p>This is an observational, retrospective study carried out at the nuclear medicine sector of the Instituto Dante Pazzanese de Cardiologia, based on the review of medical records, analyzing consecutive 500 MPS of women performed in 2011 and 2012. This study was approved by the committee of ethics and research (02020312.7.0000.5462). All patients provided written informed consent before undergoing MPS.</p><p>Exercise and pharmacological (dipyridamole and dobutamine) stress test and acquisition and processing of nuclear medicine images were performed by using standard techniques, according to the guidelines of the Brazilian Society of Cardiology/Department of Ergometry, Exercise, Nuclear Cardiology and Cardiovascular Rehabilitation<sup>15,16</sup>.</p><p>Myocardial perfusion scintigraphy was performed by use of the gated-SPECT technique, one-day protocol, the baseline phase being followed by the stress phase. A GE Ventri dedicated cardiac gamma camera was used for image acquisition. To assess myocardial perfusion, the myocardium was divided into 17 segments. Normal perfusion was considered the absence of reduced uptake of the radiotracer in both phases (baseline and stress); perfusion suggestive of ischemia and fibrosis was considered the presence of reversible and fixed reduced uptake of the radiotracer after the stress phase as compared to the baseline phase, at least in 3 of the 17 myocardial segments analyzed<sup>15</sup>.</p><p>The qualitative visual analysis of the presence or absence of perfusion alterations was performed by two observers specialized in cardiology and nuclear medicine, and, in case of disagreement, a third observer also specialized in cardiology and nuclear medicine was consulted.</p><p>This study considered the presence of myocardial ischemia on scintigraphy. Of all patients assessed, 69 had perfusion alterations suggestive of myocardial fibrosis, 41 of whom were postmenopausal women and 28, premenopausal (p = 0.069).</p><p>The patients were classified as pre/postmenopausal according to data in medical records.</p><p>The classical cardiovascular risk factors assessed were arterial hypertension, diabetes mellitus, dyslipidemia, smoking and obesity, defined according to the Brazilian Society of Cardiology guidelines<sup>17</sup>.</p><p>Patients with known CAD were those with previous diagnosis of myocardial infarction, unstable/stable angina and percutaneous or surgical myocardial revascularization. In addition, patients with the following characteristics were considered to be at equivalent high cardiovascular risk: stroke; carotid and peripheral artery disease; abdominal aorta aneurysm; and chronic renal failure<sup>17</sup>.</p><p>Patients with non-ischemic heart diseases and those with no information regarding menopause in their medical records were excluded. </p><p>Statistical analysis was performed with Fisher exact test and univariate and multivariate analyses, and the significance level adopted was p <underline>&lt;</underline> 0.05.</p><p><bold>Results</bold></p><p><xref ref-type="table" rid="en_aop_5455tab01-body2">Table 1</xref> shows the clinical and epidemiological characteristics of the patients assessed according to their menopausal status.</p><p content-type="asset"><table-wrap id="en_aop_5455tab01-body2"><graphic xlink:href="1678-4170-abc-101-06-0487-30221-gt01-en.jpg"/></table-wrap></p><p>The physicians of the outpatient clinics where the patients were followed up requested the MPS according to clinical indications. Such indications were divided into symptomatic and asymptomatic patients (<xref ref-type="table" rid="en_aop_5455tab02-body2">Tables 2</xref> and <xref ref-type="table" rid="en_aop_5455tab03-body2">3</xref>). <xref ref-type="table" rid="en_aop_5455tab04-body2">Table 4</xref> shows the results of the MPS in asymptomatic patients.</p><p content-type="asset"><table-wrap id="en_aop_5455tab02-body2"><graphic xlink:href="1678-4170-abc-101-06-0487-30221-gt02-en.jpg"/></table-wrap></p><p content-type="asset"><table-wrap id="en_aop_5455tab03-body2"><graphic xlink:href="1678-4170-abc-101-06-0487-30221-gt03-en.jpg"/></table-wrap></p><p content-type="asset"><table-wrap id="en_aop_5455tab04-body2"><graphic xlink:href="1678-4170-abc-101-06-0487-30221-gt04-en.jpg"/></table-wrap></p><p><xref ref-type="table" rid="en_aop_5455tab05_07-body2">Tables 5 to 7</xref> show the number of exercise stress tests and dipyridamole and dobutamine stress tests performed according to the menopausal status of the patients, as well as patients' clinical and electrocardiographic characteristics, and physical fitness and functional capacity.</p><p><table-wrap id="en_aop_5455tab05_07-body2"><graphic xlink:href="1678-4170-abc-101-06-0487-30221-gt05-en.jpg"/></table-wrap>&#13;
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 <p>The degree of physical fitness, known as functional capacity, measured in metabolic equivalents (MET) on the exercise test was significantly lower in postmenopausal women. Of all patients, 91 reached 10 MET or less, 56 were postmenopausal and 35, premenopausal (p &lt; 0.005). The only variable predictive of ischemia on MPS was the presence of previous CAD (p &lt; 0.05). </p> <p>Of the 500 patients assessed with MPS, ischemia was identified in 102 (58.5%) postmenopausal patients and in 72 (41.5%) premenopausal patients, with no statistical significance (p = 0.395).</p> <p><xref ref-type="fig" rid="en_aop_5455fig01-body2">Figure 1</xref>: Findings suggesting ischemia on the dipyridamole MPS of a 46-year-old female patient with diabetes, hypertension, obesity, dyslipidemia, sedentary lifestyle, and known CAD (stent in the anterior descending artery for three years): ECG showing ST-segment depression during the infusion of dipyridamole; and myocardial perfusion showing transient reduction in radiotracer uptake in the anterior, anteroseptal and apical walls. </p><p content-type="asset"><fig id="en_aop_5455fig01-body2"><graphic xlink:href="1678-4170-abc-101-06-0487-30221-gf01-en.jpg"/></fig></p>   <p><bold>Discussion</bold></p> <p>Diagnosing CAD in the female sex is a great challenge. Because its symptoms are less typical in women, non-invasive tests have an unquestionable value for its effective investigation in women before submitting them to invasive, sometimes unnecessary, tests. In the Coronary Artery Surgery Study (CASS), half of the women submitted to coronary angiography showed no significant lesions<sup>17</sup>.</p> <p>As our institution is a tertiary cardiological hospital, women followed up there usually have multiple risk factors for CAD, and most of them already had a previous myocardial infarction and/or myocardial revascularization procedure (as reported in this study, 34% with previous known CAD). Thus, we decided to carry out a study reflecting the reality of women referred for MPS, and those with previous CAD were not excluded. </p> <p>The objective of this study was to assess whether menopause was an independent predictor of ischemia in women at our institution, with and without known CAD. </p> <p>It is worth emphasizing that, in our study, many women had previous electrocardiographic alterations on baseline ECG and low functional capacity, which motivated their referral for MPS, aimed at diagnostic investigation and cardiovascular risk stratification.</p> <p>As already observed, the choice and interpretation of non-invasive procedures are not easy tasks. Exercise testing is known to have lower sensitivity and specificity in the female sex than in the male sex<sup>18</sup>. The sensitivity and specificity of the pharmacological or exercise stress tests can be improved by imaging methods that increase diagnostic accuracy<sup>10,11,18</sup>. With the refinement of the technique, a reduction in attenuation artifacts (breast, for example) was observed, leading to greater specificity<sup>13</sup>.</p> <p>In the present study, MPS proved to be an important tool to investigate ischemia, which was observed in 35% of the women assessed. Such data are in accordance with those of the literature. Smanio et al<sup>11</sup>, studying the MPS of 104 asymptomatic diabetic women, have reported myocardial ischemia in 34 (32.7%).</p> <p>Myocardial scintigraphy plays a role in CAD diagnosis and cardiovascular risk stratification in both sexes, considering that it provides information on myocardial perfusion, left ventricular function and, if necessary, myocardial viability. Its combination with exercise testing, particularly in the female sex, significantly increases diagnostic accuracy<sup>7,19</sup>.</p> <p>Mieres et al<sup>20 </sup>have assessed 46 postmenopausal women with exercise test and MPS, and the sensitivity and specificity values found were, respectively, 67% and 69% for the exercise test, and 88% and 87.5%, for MPS (p &lt; 0.0001). </p> <p>The prognostic importance of scintigraphy in the female sex is well known<sup>9,21</sup>. There is a large body of evidence on the association of myocardial scintigraphy and stress testing, showing that it effectively stratifies the risk in women suspected of having CAD. Women with a normal myocardial perfusion study have an annual event rate much lower (0.6% per year) than those with abnormal myocardial perfusion study (5% per year)<sup>22</sup>.</p> <p>The lower cardiovascular risk in the premenopausal phase is attributed to the protection provided by plasma estrogen levels<sup>23,24</sup>. Such levels promote arterial vasodilation by increasing the nitric oxide synthesis by endothelial cells, increase HDL-cholesterol particles and decrease LDL-cholesterol particles, and reduce the serum levels of fibrinogen, antithrombin and protein S<sup>24</sup>.</p> <p>The decreased estrogen levels of the postmenopausal phase lead to microvascular endothelial dysfunction and consequent progression of the atherosclerotic plaque<sup>23,24</sup>. Differently from the endogenous estrogen effects, exogenous hormone therapy has shown to increase the cardiovascular disease risks<sup>23-26</sup>.</p> <p>In 2002, the Women's Health Initiative (WHI) study showed that the benefits of hormone replacement therapy (HRT) were restricted to a small group of women in the so-called "window of opportunity", at the beginning of menopause (between 50 and 59 years), in the presence of no cardiovascular risk factors. Recent studies have confirmed that information<sup>27</sup>. However, a recent publication of the American Heart Association (AHA) contra-indicates the use of HRT as primary and secondary prevention of cardiovascular diseases<sup>28</sup>.</p> <p>Leuzzi et al<sup>29</sup>, in an interesting editorial, have reported that, despite the higher prevalence of CAD after menopause, further studies are required to clarify whether menopause is a cardiovascular risk factor.</p> <p>The association between menopause and presence of CAD might be observed in low-risk women, but for those with multiple risk factors, such as diabetes, hypertension, dyslipidemia, obesity, sedentary lifestyle, as seen in our study, menopause might not be a predictive factor of ischemia. These same findings have been observed by Sood et al<sup>14</sup> when assessing 2,194 pre- and postmenopausal women at an intermediate risk for CAD according to Duke score on exercise testing and according to MPS. In that study, menopause has not proved to predict cardiovascular events, and MPS provided risk stratification beyond the Duke score. A study with a larger number of patients should be performed to confirm that statement.</p>   <p><bold>Conclusion</bold></p> <p>The results obtained suggest that, in women with multiple risk factors for CAD, menopause was not an independent predictor of ischemia on Tc<sup>99m</sup>-sestamibi MPS. The only proven predictor in that group was the presence of known CAD. Those data support the idea that the investigation of ischemia via MPS in women with multiple risk factors for CAD should begin prior to menopause.</p>   <p><bold>Author contributions</bold></p> <p>Conception and design of the research, Acquisition of data, Analysis and interpretation of the data, Statistical analysis, Writing of the manuscript, Critical revision of the manuscript for intellectual content: Santos DAM, Sierralta WY, Alexandre LM, Smanio PEP, Cestari PF.</p> <p><bold>Potential Conflict of Interest</bold></p> <p>No potential conflict of interest relevant to this article was reported. </p> <p><bold>Sources of Funding</bold></p> <p>There were no external funding sources for this study.</p> <p><bold>Study Association</bold></p> <p>This article is part of the thesis of specialization in Cardiology submitted by Daniel Augusto Massage dos Santos e Wendy Yasdin Sierraalta by Institute Dante Pazzanese.</p>   <p><bold>References</bold></p>                            </body>
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