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  <front>
    <journal-meta>
      <journal-id journal-id-type="nlm-ta">Arq Bras Cardiol</journal-id>
      <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>
    </journal-meta>
    <article-meta>
      <article-id specific-use="scielo-v3" pub-id-type="publisher-id">x3gGf3xfXWcCqWZQQ7CxYHz</article-id>
      <article-id specific-use="scielo-v2" pub-id-type="publisher-id">S0066-782X2026000600603</article-id>
      <article-id pub-id-type="other">00603</article-id>
      <article-id pub-id-type="doi">10.36660/abc.20260060</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Artigo Original</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Epidemiologia e Mortalidade da Doen&#231;a Valvar Card&#237;aca em Adultos Brasileiros: Achados da Coorte ELSA-Brasil</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Schmitz</surname>
            <given-names>Guilia Bevilacqua</given-names>
          </name>
          <role>Concep&#231;&#227;o e desenho da pesquisa</role>
          <role>Obten&#231;&#227;o de dados</role>
          <role>An&#225;lise e interpreta&#231;&#227;o dos dados e An&#225;lise estat&#237;stica</role>
          <role>Reda&#231;&#227;o do manuscrito</role>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Pianca</surname>
            <given-names>Eduardo Gatti</given-names>
          </name>
          <role>Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do intelectual importante</role>
          <xref ref-type="aff" rid="aff2">
            <sup>2</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Nunes</surname>
            <given-names>Maria Do Carmo Pereira</given-names>
          </name>
          <role>Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do intelectual importante</role>
          <xref ref-type="aff" rid="aff3">
            <sup>3</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Duncan</surname>
            <given-names>Bruce Bartholow</given-names>
          </name>
          <role>Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do intelectual importante</role>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
          <xref ref-type="aff" rid="aff4">
            <sup>4</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0003-2914-4406</contrib-id>
          <name>
            <surname>Foppa</surname>
            <given-names>Murilo</given-names>
          </name>
          <role>Concep&#231;&#227;o e desenho da pesquisa</role>
          <role>Obten&#231;&#227;o de dados</role>
          <role>An&#225;lise e interpreta&#231;&#227;o dos dados e An&#225;lise estat&#237;stica</role>
          <role>Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do intelectual importante</role>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
          <xref ref-type="aff" rid="aff2">
            <sup>2</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0003-2493-0547</contrib-id>
          <name>
            <surname>Santos</surname>
            <given-names>Angela Barreto Santiago</given-names>
          </name>
          <role>Concep&#231;&#227;o e desenho da pesquisa</role>
          <role>Obten&#231;&#227;o de dados</role>
          <role>An&#225;lise e interpreta&#231;&#227;o dos dados e An&#225;lise estat&#237;stica</role>
          <role>Reda&#231;&#227;o do manuscrito</role>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
          <xref ref-type="aff" rid="aff2">
            <sup>2</sup>
          </xref>
        </contrib>
      </contrib-group>
      <aff id="aff1">
        <label>1</label>
        <institution content-type="orgdiv1">Faculdade de Medicina</institution>
        <institution content-type="orgname">Universidade Federal do Rio Grande do Sul</institution>
        <addr-line>
          <named-content content-type="city">Porto Alegre</named-content>
          <named-content content-type="state">RS</named-content>
        </addr-line>
        <country country="BR">Brasil</country>
        <institution content-type="original">P&#243;s-Gradua&#231;&#227;o em Cardiologia e Ci&#234;ncias Cardiovasculares &#8211; Faculdade de Medicina &#8211; Universidade Federal do Rio Grande do Sul, Porto Alegre, RS &#8211; Brasil</institution>
      </aff>
      <aff id="aff2">
        <label>2</label>
        <institution content-type="orgname">Hospital de Cl&#237;nicas de Porto Alegre</institution>
        <addr-line>
          <named-content content-type="city">Porto Alegre</named-content>
          <named-content content-type="state">RS</named-content>
        </addr-line>
        <country country="BR">Brasil</country>
        <institution content-type="original">Servi&#231;o de Cardiologia, Hospital de Cl&#237;nicas de Porto Alegre, Porto Alegre, RS &#8211; Brasil</institution>
      </aff>
      <aff id="aff3">
        <label>3</label>
        <institution content-type="orgdiv1">Faculdade de Medicina</institution>
        <institution content-type="orgdiv2">Hospital das Cl&#237;nicas</institution>
        <institution content-type="orgname">Universidade Federal de Minas Gerais</institution>
        <addr-line>
          <named-content content-type="city">Belo Horizonte</named-content>
          <named-content content-type="state">MG</named-content>
        </addr-line>
        <country country="BR">Brasil</country>
        <institution content-type="original">Faculdade de Medicina, Hospital das Cl&#237;nicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG &#8211; Brasil</institution>
      </aff>
      <aff id="aff4">
        <label>4</label>
        <institution content-type="orgname">Universidade Federal do Rio Grande do Sul</institution>
        <addr-line>
          <named-content content-type="city">Porto Alegre</named-content>
          <named-content content-type="state">RS</named-content>
        </addr-line>
        <country country="BR">Brasil</country>
        <institution content-type="original">P&#243;s-Gradua&#231;&#227;o em Epidemiologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS &#8211; Brasil</institution>
      </aff>
      <author-notes>
        <corresp id="c01"><label>Correspond&#234;ncia:</label>Angela Barreto Santiago Santos Hospital de Clinicas de Porto Alegre &#8211; Cardiologia - Rua Ramiro Barcelos, 2350, Sala 2061. CEP 90035-903, Porto Alegre, RS &#8211; Brasil. E-mail: <email>abssantos@hcpa.edu.br</email> </corresp>
        <fn fn-type="edited-by">
          <label>Editor respons&#225;vel pela revis&#227;o:</label>
          <p>Ana Teresa Tim&#243;teo</p>
        </fn>
        <fn fn-type="coi-statement">
          <label>Potencial Conflito de Interesse:</label>
          <p>Declaro n&#227;o haver conflito de interesses pertinentes.</p>
        </fn>
      </author-notes>
      <pub-date date-type="pub" publication-format="electronic">
        <day>24</day>
        <month>07</month>
        <year>2026</year>
      </pub-date>
      <pub-date date-type="collection" publication-format="electronic">
        <year>2026</year>
      </pub-date>
      <volume>123</volume>
      <issue>6</issue>
      <elocation-id>e20260060</elocation-id>
      <history>
        <date date-type="received">
          <day>29</day>
          <month>01</month>
          <year>2026</year>
        </date>
        <date date-type="rev-recd">
          <day>20</day>
          <month>04</month>
          <year>2026</year>
        </date>
        <date date-type="accepted">
          <day>29</day>
          <month>04</month>
          <year>2026</year>
        </date>
      </history>
      <permissions>
        <license license-type="open-access" xlink:href="https://creativecommons.org/licenses/by/4.0/" xml:lang="pt">
          <license-p>Este &#233; um artigo de acesso aberto distribu&#237;do sob os termos da licen&#231;a de atribui&#231;&#227;o pelo Creative Commons</license-p>
        </license>
      </permissions>
      <abstract>
        <title>Resumo</title>
        <sec>
          <title>Fundamento</title>
          <p> A maior parte das evid&#234;ncias atuais sobre doen&#231;a valvar card&#237;aca (DVC) vem de pa&#237;ses de alta renda. O acesso ao tratamento e o impacto da DVC na qualidade de vida podem variar substancialmente entre pa&#237;ses, principalmente devido a diferen&#231;as socioecon&#244;micas.</p>
        </sec>
        <sec>
          <title>Objetivo</title>
          <p> Este estudo teve como objetivo estimar a carga de DVC e sua associa&#231;&#227;o com mortalidade em um pa&#237;s de renda m&#233;dia.</p>
        </sec>
        <sec>
          <title>M&#233;todos</title>
          <p> Inclu&#237;mos participantes da coorte ELSA-Brasil que realizaram ecocardiograma transtor&#225;cico na linha de base (3.267 participantes; 1.539 homens; idade m&#233;dia de 60,6 &#177; 8,8 anos) em seis estados brasileiros. Os participantes foram categorizados em tr&#234;s grupos &#8211; sem DVC, DVC m&#237;nima/leve e DVC moderada/grave &#8211; e suas caracter&#237;sticas e fatores associados foram analisados. Valores de p &lt; 0,05 foram considerados estatisticamente significativos.</p>
        </sec>
        <sec>
          <title>Resultados</title>
          <p> Entre todos os participantes, 2,4% apresentavam DVC moderada/grave (incluindo sete participantes com pr&#243;tese valvar) e 43,6% apresentavam DVC m&#237;nima/leve. A DVC moderada/grave mais prevalente foi a regurgita&#231;&#227;o mitral, seguida pelas regurgita&#231;&#245;es a&#243;rtica e tric&#250;spide, com 56 participantes (86%) apresentando regurgita&#231;&#227;o valvar isolada. A DVC moderada/grave foi mais comum em indiv&#237;duos mais velhos e esteve associada a maior preval&#234;ncia da maioria das comorbidades cardiovasculares, por&#233;m a menores taxas de obesidade. Tamb&#233;m se associou a maior remodelamento card&#237;aco e pior fun&#231;&#227;o sist&#243;lica, com varia&#231;&#245;es fenot&#237;picas conforme a valva acometida. A DVC moderada/grave esteve associada a maior mortalidade em 10 anos (HR: 3,7; IC 95% [2,17&#8211;6,31]), independentemente de idade, sexo e hipertens&#227;o.</p>
        </sec>
        <sec>
          <title>Conclus&#227;o</title>
          <p> A DVC &#233; comum entre adultos em uma coorte comunit&#225;ria de um pa&#237;s de renda m&#233;dia e aumenta com a idade. Participantes com DVC moderada/grave apresentaram maior carga de comorbidades, remodelamento card&#237;aco mais acentuado, pior fun&#231;&#227;o sist&#243;lica e redu&#231;&#227;o substancial da sobrevida em longo prazo.</p>
        </sec>
      </abstract>
      <abstract abstract-type="graphical">
        <p>
          <fig id="f01">
            <label>Figura Central</label>
            <caption>
              <title>: Epidemiologia e Mortalidade da Doen&#231;a Valvar Card&#237;aca em Adultos Brasileiros: Achados da Coorte ELSA-Brasil</title>
            </caption>
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      </abstract>
      <kwd-group xml:lang="pt">
        <title>Palavras-chave:</title>
        <kwd>Doen&#231;as das Valvas Card&#237;acas</kwd>
        <kwd>Epidemiologia</kwd>
        <kwd>Mortalidade</kwd>
        <kwd>Adulto</kwd>
      </kwd-group>
      <funding-group>
        <award-group>
          <funding-source>Minist&#233;rio da Ci&#234;ncia, Tecnologia e Inova&#231;&#227;o</funding-source>
          <award-id>01 06 0010.00</award-id>
        </award-group>
        <award-group>
          <funding-source>Minist&#233;rio da Ci&#234;ncia, Tecnologia e Inova&#231;&#227;o</funding-source>
          <award-id>01 10 0643.00 RS</award-id>
        </award-group>
        <award-group>
          <funding-source>Minist&#233;rio da Ci&#234;ncia, Tecnologia e Inova&#231;&#227;o</funding-source>
          <award-id>01 06 0212.00 BA</award-id>
        </award-group>
        <award-group>
          <funding-source>Minist&#233;rio da Ci&#234;ncia, Tecnologia e Inova&#231;&#227;o</funding-source>
          <award-id>01 06 0300.00 ES</award-id>
        </award-group>
        <award-group>
          <funding-source>Minist&#233;rio da Ci&#234;ncia, Tecnologia e Inova&#231;&#227;o</funding-source>
          <award-id>01 06 0278.00 MG</award-id>
        </award-group>
        <award-group>
          <funding-source>Minist&#233;rio da Ci&#234;ncia, Tecnologia e Inova&#231;&#227;o</funding-source>
          <award-id>01 06 0115.00 SP</award-id>
        </award-group>
        <award-group>
          <funding-source>Minist&#233;rio da Ci&#234;ncia, Tecnologia e Inova&#231;&#227;o</funding-source>
          <award-id>01 06 0071.00 RJ</award-id>
        </award-group>
        <funding-statement><bold>Fontes de Financiamento:</bold> O presente estudo foi financiado pelo Minist&#233;rio da Sa&#250;de do Brasil (Departamento de Ci&#234;ncia e Tecnologia) e pelo Minist&#233;rio da Ci&#234;ncia, Tecnologia e Inova&#231;&#227;o (Financiadora de Estudos e Projetos &#8211; concess&#245;es 01 06 0010.00, 01 10 0643.00 RS, 01 06 0212.00 BA, 01 06 0300.00 ES, 01 06 0278.00 MG, 01 06 0115.00 SP, 01 06 0071.00 RJ), bem como pelo CNPq (Conselho Nacional de Desenvolvimento Cient&#237;fico e Tecnol&#243;gico).</funding-statement>
      </funding-group>
      <counts>
        <fig-count count="6"/>
        <table-count count="4"/>
        <equation-count count="0"/>
        <ref-count count="22"/>
      </counts>
    </article-meta>
  </front>
  <body>
    <sec sec-type="intro">
      <title>Introdu&#231;&#227;o</title>
      <p>A doen&#231;a valvar card&#237;aca (DVC) &#233; uma condi&#231;&#227;o card&#237;aca prevalente, associada ao aumento da morbidade e mortalidade,<sup><xref ref-type="bibr" rid="B1">1</xref>-<xref ref-type="bibr" rid="B3">3</xref></sup> e sua preval&#234;ncia aumenta com a idade.<sup><xref ref-type="bibr" rid="B4">4</xref>-<xref ref-type="bibr" rid="B6">6</xref></sup> Embora a maioria dos pacientes apresente DVC leve e assintom&#225;tica, aqueles com doen&#231;a moderada ou grave podem desenvolver complica&#231;&#245;es significativas, incluindo insufici&#234;ncia card&#237;aca e morte.<sup><xref ref-type="bibr" rid="B2">2</xref>,<xref ref-type="bibr" rid="B3">3</xref></sup> Al&#233;m disso, o impacto da DVC na qualidade de vida e no acesso ao tratamento varia de acordo com o contexto socioecon&#244;mico de cada pa&#237;s.</p>
      <p>Diversos fatores j&#225; foram associados a diferentes tipos de DVC. A regurgita&#231;&#227;o mitral est&#225; relacionada &#224; idade avan&#231;ada, sexo feminino, hipertens&#227;o, redu&#231;&#227;o da fra&#231;&#227;o de eje&#231;&#227;o (FE) do ventr&#237;culo esquerdo (VE) e menor &#237;ndice de massa corporal (IMC).<sup><xref ref-type="bibr" rid="B2">2</xref>,<xref ref-type="bibr" rid="B5">5</xref>,<xref ref-type="bibr" rid="B7">7</xref></sup> A regurgita&#231;&#227;o tric&#250;spide pode estar associada &#224; idade avan&#231;ada, sexo feminino, IMC reduzido, consumo de &#225;lcool, n&#237;veis mais altos de HDL-colesterol, frequ&#234;ncia card&#237;aca elevada, disfun&#231;&#227;o do VE, doen&#231;a card&#237;aca do lado esquerdo e aumento do &#225;trio esquerdo.<sup><xref ref-type="bibr" rid="B6">6</xref>-<xref ref-type="bibr" rid="B8">8</xref></sup> J&#225; a regurgita&#231;&#227;o a&#243;rtica est&#225; principalmente associada &#224; idade avan&#231;ada, sexo masculino, press&#227;o arterial sist&#243;lica elevada, dilata&#231;&#227;o da raiz a&#243;rtica e aumento do &#237;ndice de massa ventricular esquerda.</p>
      <p>A maioria dos dados dispon&#237;veis sobre DVC vem de pa&#237;ses de alta renda, e evid&#234;ncias populacionais da Am&#233;rica Latina continuam escassas, dificultando a estimativa precisa da carga de DVC nessa regi&#227;o. A coorte ELSA-Brasil oferece uma oportunidade &#250;nica para obter estimativas confi&#225;veis da preval&#234;ncia e dos desfechos da DVC, al&#233;m de avaliar o impacto da transi&#231;&#227;o epidemiol&#243;gica em curso em um pa&#237;s de renda m&#233;dia. Portanto, o presente estudo teve como objetivo investigar: 1) a preval&#234;ncia de DVC em uma popula&#231;&#227;o adulta brasileira de base comunit&#225;ria; 2) os determinantes cl&#237;nicos e demogr&#225;ficos da DVC; 3) o fen&#243;tipo ecocardiogr&#225;fico de cada DVC moderada/grave; e 4) o impacto da DVC moderada/grave na mortalidade em longo prazo.</p>
    </sec>
    <sec sec-type="materials|methods">
      <title>Materiais e M&#233;todos</title>
      <sec>
        <title>Popula&#231;&#227;o do estudo</title>
        <p>O Estudo Longitudinal de Sa&#250;de do Adulto (ELSA-Brasil) &#233; um estudo epidemiol&#243;gico prospectivo desenvolvido para investigar doen&#231;as cardiovasculares e diabetes em 15.105 servidores p&#250;blicos, homens e mulheres, de universidades ou institui&#231;&#245;es de pesquisa localizadas em seis cidades brasileiras (S&#227;o Paulo, Rio de Janeiro, Belo Horizonte, Vit&#243;ria, Salvador e Porto Alegre). Todos os funcion&#225;rios ativos ou aposentados, com idades entre 35 e 74 anos, eram eleg&#237;veis para participar. Os detalhes do estudo &#8212; incluindo desenho, crit&#233;rios de elegibilidade, recrutamento e avalia&#231;&#245;es &#8212; foram descritos previamente.<sup><xref ref-type="bibr" rid="B9">9</xref>,<xref ref-type="bibr" rid="B10">10</xref></sup></p>
        <p>Uma subamostra aleat&#243;ria da coorte foi definida <italic>a priori</italic> para an&#225;lises do tipo caso-coorte. Essa amostra aleat&#243;ria (n = 1.543) correspondeu a 10% do total da coorte, selecionada utilizando os mesmos crit&#233;rios de estratifica&#231;&#227;o aplicados &#224; amostra completa (sexo, faixa et&#225;ria e categoria ocupacional). Um n&#250;mero aleat&#243;rio gerado por computador foi atribu&#237;do a cada participante, e os 10% menores n&#250;meros dentro de cada estrato foram selecionados. Dessa amostra aleat&#243;ria, ecocardiogramas transtor&#225;cicos (ETT) foram obtidos durante a primeira visita do estudo em 1.172 participantes.</p>
        <p>Para a presente an&#225;lise, inclu&#237;mos todos os participantes da coorte que realizaram ETT basal (agosto de 2008 a dezembro de 2010), priorizando todos os indiv&#237;duos com 60 anos ou mais (N = 2.095), bem como a subamostra aleat&#243;ria predefinida correspondente a 10% de toda a coorte (N = 1.172) (<xref ref-type="sec" rid="suppl">Material Suplementar &#8211; Figura 1</xref>).</p>
        <p>Os dados de mortalidade por todas as causas at&#233; dezembro de 2022 foram coletados por meio de acompanhamento telef&#244;nico anual e confirmados por revis&#227;o de prontu&#225;rios m&#233;dicos, certid&#245;es de &#243;bito e vincula&#231;&#227;o a bases de dados nacionais, como o Sistema de Informa&#231;&#245;es sobre Mortalidade.</p>
        <p>O estudo ELSA-Brasil est&#225; em conformidade com os princ&#237;pios da Declara&#231;&#227;o de Helsinque e foi aprovado pelos comit&#234;s de &#233;tica em pesquisa das institui&#231;&#245;es participantes. Todos os participantes forneceram consentimento informado por escrito.</p>
      </sec>
      <sec>
        <title>Ecocardiografia</title>
        <p>Todos os ecocardiogramas transtor&#225;cicos foram realizados durante a primeira visita do estudo. As imagens foram adquiridas utilizando aparelhos de ecocardiografia configurados de forma id&#234;ntica (Aplio XG, Toshiba, Jap&#227;o), equipados com transdutor setorial de 2,5 MHz, seguindo protocolos padronizados. Os exames foram gravados em formato digital e transferidos para o Centro de Leitura de Ecocardiografia do ELSA-Brasil, em Porto Alegre, Brasil. Par&#226;metros ecocardiogr&#225;ficos e Doppler padr&#227;o foram analisados em uma esta&#231;&#227;o de trabalho offline (ComPACS 10.5; Medimatic SrL, It&#225;lia). Todas as medidas foram realizadas em triplicata, de acordo com as recomenda&#231;&#245;es da <italic>American Society of Echocardiography</italic>,<sup><xref ref-type="bibr" rid="B11">11</xref></sup> e inclu&#237;ram di&#226;metros e volumes do ventr&#237;culo esquerdo (VE), espessura das paredes do VE, massa ventricular esquerda, fra&#231;&#227;o de eje&#231;&#227;o do VE e volume e di&#226;metro do &#225;trio esquerdo (AE).</p>
        <p>A gravidade da DVC foi inicialmente sinalizada pelo ecocardiografista treinado durante a aquisi&#231;&#227;o das imagens, e imagens adicionais al&#233;m do protocolo pr&#233;-definido foram obtidas a crit&#233;rio do operador para melhor caracteriza&#231;&#227;o da DVC, incluindo avalia&#231;&#227;o de prolapso da valva mitral e morfologia de valva a&#243;rtica bic&#250;spide. Todas as imagens foram posteriormente revisadas no centro de leitura (independentemente de terem sido sinalizadas inicialmente) e avaliadas qualitativamente com base nos achados de Doppler colorido e Doppler espectral, seguindo crit&#233;rios aplicados em estudos populacionais anteriores.<sup><xref ref-type="bibr" rid="B12">12</xref></sup></p>
        <p>Al&#233;m disso, a defini&#231;&#227;o de estenose a&#243;rtica (EA) foi baseada na velocidade sist&#243;lica anter&#243;grada atrav&#233;s da valva a&#243;rtica, enquanto a classifica&#231;&#227;o da estenose mitral (EM) foi baseada no gradiente m&#233;dio transmitral.</p>
        <p>O protocolo do estudo teve como objetivo espec&#237;fico identificar prolapso da valva mitral, definido como espessura m&#225;xima do folheto &gt;5 mm e deslocamento sist&#243;lico &gt;2 mm al&#233;m do plano do anel na vis&#227;o paraesternal, bem como a morfologia de valva a&#243;rtica bic&#250;spide, caracterizada por coapta&#231;&#227;o exc&#234;ntrica dos folhetos, presen&#231;a de dois folhetos durante a s&#237;stole e orif&#237;cio sist&#243;lico el&#237;ptico. A hipertens&#227;o pulmonar foi definida como gradiente &#225;trio direito&#8211;ventr&#237;culo direito (AD&#8211;VD) &gt;25 mmHg.</p>
      </sec>
      <sec>
        <title>An&#225;lise estat&#237;stica</title>
        <p>Classificamos os participantes em tr&#234;s grupos: sem DVC, DVC m&#237;nima/leve e DVC moderada/grave. As vari&#225;veis cont&#237;nuas s&#227;o apresentadas como mediana e intervalo interquartil e foram comparadas utilizando o teste de Kruskal&#8211;Wallis. Quando o valor de p global foi &lt;0,05, compara&#231;&#245;es p&#243;s-hoc pareadas foram realizadas usando o teste de Dunn com corre&#231;&#227;o de Bonferroni para m&#250;ltiplas compara&#231;&#245;es. As vari&#225;veis categ&#243;ricas s&#227;o apresentadas como contagens e propor&#231;&#245;es e foram comparadas utilizando o teste exato de Fisher, seguido por testes exatos de Fisher pareados quando o valor de p global foi &lt;0,05, com valores de p ajustados pelo m&#233;todo de Bonferroni.</p>
        <p>Cada doen&#231;a valvar foi analisada ao longo das d&#233;cadas de idade utilizando o teste n&#227;o param&#233;trico de tend&#234;ncia de Cuzick (nptrend). Os correlatos relevantes das DVC moderadas/graves mais prevalentes &#8211; regurgita&#231;&#227;o mitral (RM), regurgita&#231;&#227;o a&#243;rtica (RA) e regurgita&#231;&#227;o tric&#250;spide (RT) &#8211; foram inicialmente explorados em an&#225;lises univariadas, seguidas por modelos de regress&#227;o log&#237;stica multivariada incluindo covari&#225;veis selecionadas a priori com base na literatura estabelecida, representando fatores de risco clinicamente distintos para doen&#231;a valvar (idade, sexo, ra&#231;a negra, tabagismo, obesidade, hipertens&#227;o e diabetes). Al&#233;m disso, avaliamos os principais par&#226;metros ecocardiogr&#225;ficos associados a fen&#243;tipos espec&#237;ficos de DVC (volume diast&#243;lico final do VE, volume sist&#243;lico final do VE, espessura relativa da parede do VE, massa ventricular esquerda, fra&#231;&#227;o de eje&#231;&#227;o do VE, &#237;ndice de volume do AE e hipertens&#227;o pulmonar), utilizando modelos de regress&#227;o log&#237;stica ajustados por idade e sexo.</p>
        <p>A sobrevida cumulativa foi estimada pelo m&#233;todo de Kaplan&#8211;Meier, e as curvas de sobrevida foram comparadas pelo teste de log-rank. Participantes com pr&#243;teses valvares foram inclu&#237;dos na preval&#234;ncia geral de DVC moderada/grave, mas exclu&#237;dos das an&#225;lises subsequentes de caracteriza&#231;&#227;o devido &#224;s altera&#231;&#245;es na hist&#243;ria natural da DVC.</p>
        <p>Todas as an&#225;lises estat&#237;sticas foram realizadas utilizando o pacote STATA (vers&#227;o 12; StataCorp, College Station, Texas). Todos os testes foram bicaudais, e valores de p &lt;0,05 foram considerados estatisticamente significativos.</p>
      </sec>
    </sec>
    <sec sec-type="results">
      <title>Resultados</title>
      <p>Nossa amostra foi composta por 3.267 participantes (1.539 homens; idade m&#233;dia de 60,6 &#177; 8,8 anos; 56% autodeclarados brancos) provenientes de seis diferentes estados do Brasil (15% do Nordeste, 63% do Sudeste e 22% do Sul). A preval&#234;ncia de hipertens&#227;o foi de 51,0%; diabetes 23,4%; sobrepeso 42,8%; obesidade 22,2%; doen&#231;a arterial coronariana 6,5%; e tabagismo 10,2% na popula&#231;&#227;o geral.</p>
      <p>Entre todos os participantes, 2,4% apresentavam DVC moderada/grave (incluindo 7 participantes com pr&#243;teses valvares) e 43,6% apresentavam DVC m&#237;nima/leve (<xref ref-type="fig" rid="f02">Figura 1</xref> e <xref ref-type="fig" rid="f01">Ilustra&#231;&#227;o Central</xref>). A DVC moderada/grave mais prevalente foi a regurgita&#231;&#227;o mitral, seguida por regurgita&#231;&#227;o a&#243;rtica e tric&#250;spide. Entre aqueles com DVC moderada/grave, 56 (86%) apresentavam regurgita&#231;&#227;o valvar isolada; 8 (12,5%) tinham doen&#231;a mista envolvendo duas valvas regurgitantes; e 1 (1,5%) apresentava doen&#231;a mista envolvendo tr&#234;s valvas regurgitantes. Estenoses moderadas/graves estavam presentes em 6 participantes (8,5% dos casos de DVC moderada/grave). Al&#233;m disso, a preval&#234;ncia de prolapso da valva mitral foi de 1,2% e de valva a&#243;rtica bic&#250;spide de 0,5%, sem diferen&#231;as significativas entre os sexos.</p>
      <p>
        <fig id="f02">
          <label>Figura 1</label>
          <caption>
            <title>&#8211; Preval&#234;ncia de doen&#231;a valvar card&#237;aca (DVC) na amostra.</title>
          </caption>
          <graphic xlink:href="1678-4170-abc-123-06-e20260060-60060-gf01.tif"/></fig>
      </p>
      <p>Participantes com mais de 55 anos apresentaram maior preval&#234;ncia tanto de DVC m&#237;nima/leve quanto de DVC moderada/grave em compara&#231;&#227;o com indiv&#237;duos mais jovens. Apenas quatro casos de DVC moderada/grave foram identificados entre participantes com menos de 55 anos, correspondendo a uma preval&#234;ncia inferior a 1% (<xref ref-type="sec" rid="suppl">Material Suplementar &#8211; Tabela 1</xref>).</p>
      <p>Os participantes com DVC moderada/grave eram mais velhos e apresentavam maior preval&#234;ncia de hipertens&#227;o, doen&#231;a arterial coronariana, insufici&#234;ncia card&#237;aca, tabagismo e <italic>flutter</italic>/fibrila&#231;&#227;o atrial, al&#233;m de menor preval&#234;ncia de obesidade e s&#237;ndrome metab&#243;lica (<xref ref-type="table" rid="t1">Tabela 1</xref>).</p>
      <p>
        <table-wrap id="t1">
          <label>Tabela 1</label>
          <caption>
            <title>&#8211; Caracter&#237;sticas demogr&#225;ficas basais e par&#226;metros ecocardiogr&#225;ficos dos participantes do ELSA-Brasil que realizaram ecocardiograma na linha de base, estratificados pela gravidade da doen&#231;a valvar card&#237;aca</title>
          </caption>
          <table frame="hsides" rules="groups">
            <colgroup>
              <col/>
              <col/>
              <col/>
              <col/>
              <col/>
            </colgroup>
            <thead>
              <tr>
                <th align="left" style="font-weight:normal"> </th>
                <th style="font-weight:normal">Sem DVC (n=1.770) </th>
                <th>DVC m&#237;nima/leve (n=1.420)</th>
                <th>DVC moderada/grave VHD (n=70)</th>
                <th>Valor p</th>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td>
                  <bold>Idade (anos)</bold>
                </td>
                <td align="center">61 (51&#8211;65)</td>
                <td align="center">64 (60-68)</td>
                <td align="center">65 (61-71)*<sup>&#8224;</sup></td>
                <td align="center">&lt;0,01</td>
              </tr>
              <tr>
                <td>
                  <bold>Sexo</bold>
                </td>
                <td> </td>
                <td> </td>
                <td> </td>
                <td> </td>
              </tr>
              <tr>
                <td>Feminino</td>
                <td align="center">909 (51,3)</td>
                <td align="center">779 (54,9)</td>
                <td align="center">38 (54,3)</td>
                <td align="center">0,13</td>
              </tr>
              <tr>
                <td>Masculino</td>
                <td align="center">861(48,6)</td>
                <td align="center">641 (45,14)</td>
                <td align="center">32 (45,7)</td>
                <td align="center">0,13</td>
              </tr>
              <tr>
                <td>
                  <bold>Categoria de cor/ra&#231;a autodeclarada</bold>
                </td>
                <td> </td>
                <td> </td>
                <td> </td>
                <td align="center">0,005</td>
              </tr>
              <tr>
                <td>Branca</td>
                <td align="center">993 (55,0)</td>
                <td align="center">783 (43,4)</td>
                <td align="center">29 (1,6)</td>
                <td> </td>
              </tr>
              <tr>
                <td>Preta</td>
                <td align="center">243 (48,9)</td>
                <td align="center">231 (46,6)</td>
                <td align="center">22 (4,4)</td>
                <td> </td>
              </tr>
              <tr>
                <td>Parda</td>
                <td align="center">442 (55,0)</td>
                <td align="center">346 (43,0)</td>
                <td align="center">16 (2,0)</td>
                <td> </td>
              </tr>
              <tr>
                <td>Amarela</td>
                <td align="center">44 (55,0)</td>
                <td align="center">35 (43,8)</td>
                <td align="center">1 (1,2)</td>
                <td> </td>
              </tr>
              <tr>
                <td>Ind&#237;gena</td>
                <td align="center">26 (68,4)</td>
                <td align="center">11 (29,0)</td>
                <td align="center">1 (2,6)</td>
                <td> </td>
              </tr>
              <tr>
                <td>
                  <bold>Centros brasileiros</bold>
                </td>
                <td> </td>
                <td> </td>
                <td> </td>
                <td align="center">&lt;0,01</td>
              </tr>
              <tr>
                <td>Bahia</td>
                <td align="center">218(44,1)</td>
                <td align="center">261(52,8)</td>
                <td align="center">15 (3,1)</td>
                <td> </td>
              </tr>
              <tr>
                <td>Esp&#237;rito Santo</td>
                <td align="center">158(56,4)</td>
                <td align="center">119(42,5)</td>
                <td align="center">2 (1,1)</td>
                <td> </td>
              </tr>
              <tr>
                <td>Minas Gerais</td>
                <td align="center">390(47,5)</td>
                <td align="center">411(50,1)</td>
                <td align="center">20 (2,4)</td>
                <td> </td>
              </tr>
              <tr>
                <td>Rio de Janeiro</td>
                <td align="center">238(75,8)</td>
                <td align="center">73(23,2)</td>
                <td align="center">3 (1,0)</td>
                <td> </td>
              </tr>
              <tr>
                <td>S&#227;o Paulo</td>
                <td align="center">377(58,9)</td>
                <td align="center">246(38,4)</td>
                <td align="center">17 (2,7)</td>
                <td> </td>
              </tr>
              <tr>
                <td>Rio Grande do Sul</td>
                <td align="center">389(54,7)</td>
                <td align="center">310(43,6)</td>
                <td align="center">12 (1,7)</td>
                <td> </td>
              </tr>
              <tr>
                <td>
                  <bold>PAS (mmHg)</bold>
                </td>
                <td align="center">122,5 (112,5-134)</td>
                <td align="center">125 (114-139)</td>
                <td align="center">132 (118-142)*</td>
                <td align="center">&lt;0,01</td>
              </tr>
              <tr>
                <td>
                  <bold>PAD (mmHg)</bold>
                </td>
                <td align="center">76 (69,5-83)</td>
                <td align="center">75,5 (69-82,5)</td>
                <td align="center">71,8 (65,5-80)*<sup>&#8224;</sup></td>
                <td align="center">&lt;0,01</td>
              </tr>
              <tr>
                <td>
                  <bold>IMC (Kg/m<sup>2</sup>)</bold>
                </td>
                <td align="center">26,9 (24,3-29,9)</td>
                <td align="center">26 (23,6-28,9)</td>
                <td align="center">25,4 (23,3-28,3)*</td>
                <td align="center">&lt;0,01</td>
              </tr>
              <tr>
                <td>
                  <bold>Sobrepeso</bold>
                </td>
                <td align="center">769 (43,5)</td>
                <td align="center">597 (42)</td>
                <td align="center">28 (40)</td>
                <td align="center">0,66</td>
              </tr>
              <tr>
                <td>
                  <bold>Obesidade</bold>
                </td>
                <td align="center">437 (24,7)</td>
                <td align="center">275 (19,4)</td>
                <td align="center">10 (14,3)*</td>
                <td align="center">&lt;0,01</td>
              </tr>
              <tr>
                <td>
                  <bold>Hipertens&#227;o</bold>
                </td>
                <td align="center">852 (48,2)</td>
                <td align="center">760 (53,6)</td>
                <td align="center">49 (70)*&#8224;</td>
                <td align="center">&lt;0,01</td>
              </tr>
              <tr>
                <td>
                  <bold>Diabetes</bold>
                </td>
                <td align="center">408 (23,1)</td>
                <td align="center">338 (23,8)</td>
                <td align="center">15 (21,4)</td>
                <td align="center">0,85</td>
              </tr>
              <tr>
                <td>
                  <bold>S&#237;ndrome metab&#243;lica</bold>
                </td>
                <td align="center">944 (53,6)</td>
                <td align="center">710 (50,1)</td>
                <td align="center">29 (41,4)</td>
                <td align="center">0,03</td>
              </tr>
              <tr>
                <td>
                  <bold>Acidente vascular cerebral</bold>
                </td>
                <td align="center">33 (1,9)</td>
                <td align="center">29 (2,0)</td>
                <td align="center">3 (4,3)</td>
                <td align="center">0,27</td>
              </tr>
              <tr>
                <td>
                  <bold>DAC</bold>
                </td>
                <td align="center">94 (5,5)</td>
                <td align="center">101 (7,3)</td>
                <td align="center">12 (17,4)*<sup>&#8224;</sup></td>
                <td align="center">&lt;0,01</td>
              </tr>
              <tr>
                <td>
                  <bold>Insufici&#234;ncia card&#237;aca</bold>
                </td>
                <td align="center">36 (2)</td>
                <td align="center">51 (3,6)</td>
                <td align="center">14 (20)*<sup>&#8224;</sup></td>
                <td align="center">&lt;0,01</td>
              </tr>
              <tr>
                <td>
                  <bold>Tabagismo</bold>
                </td>
                <td align="center">220 (12,4)</td>
                <td align="center">107 (7,5)</td>
                <td align="center">6 (8,6)</td>
                <td align="center">&lt;0,01</td>
              </tr>
              <tr>
                <td>
                  <bold>Flutter/fibrila&#231;&#227;o atrial</bold>
                </td>
                <td align="center">6 (0,3)</td>
                <td align="center">17 (1,2)</td>
                <td align="center">4 (5,7)*<sup>&#8224;</sup></td>
                <td align="center">&lt;0,01</td>
              </tr>
              <tr>
                <td>
                  <bold>Di&#226;metro diast&#243;lico do VE, mm</bold>
                </td>
                <td align="center">45 (42-48)</td>
                <td align="center">45 (41-48)</td>
                <td align="center">50 (45-56)*<sup>&#8224;</sup></td>
                <td align="center">&lt;0,01</td>
              </tr>
              <tr>
                <td>
                  <bold>Di&#226;metro sist&#243;lico do VE, mm</bold>
                </td>
                <td align="center">28 (25-30)</td>
                <td align="center">28 (25-31)</td>
                <td align="center">31 (29-40)*<sup>&#8224;</sup></td>
                <td align="center">&lt;0,01</td>
              </tr>
              <tr>
                <td>
                  <bold>Espessura do septo</bold>
                </td>
                <td align="center">10 (9-11)</td>
                <td align="center">10 (9-11)</td>
                <td align="center">10 (9-12)*</td>
                <td align="center">&lt;0,01</td>
              </tr>
              <tr>
                <td>
                  <bold>Espessura da parede posterior, mm</bold>
                </td>
                <td align="center">9 (8-10)</td>
                <td align="center">9 (8-10)</td>
                <td align="center">9 (8-10)</td>
                <td align="center">0,5</td>
              </tr>
              <tr>
                <td>
                  <bold>Espessura relativa da Parede do VE</bold>
                </td>
                <td align="center">0,42 (0,38-0,47)</td>
                <td align="center">0,42 (0,38-0,48)</td>
                <td align="center">0,38 (0,34-0,44)*<sup>&#8224;</sup></td>
                <td align="center">&lt;0,01</td>
              </tr>
              <tr>
                <td>
                  <bold>Massa do VE, g</bold>
                </td>
                <td align="center">138,7 (114,7-167,5)</td>
                <td align="center">140 (116,8-170,8)</td>
                <td align="center">177,8 (131,6-242,2)*<sup>&#8224;</sup></td>
                <td align="center">&lt;0,01</td>
              </tr>
              <tr>
                <td>
                  <bold>Volume diast&#243;lico do VE, mL</bold>
                </td>
                <td align="center">89,1 (77,9-101,6)</td>
                <td align="center">89,3 (77,3-103,9)</td>
                <td align="center">112,1 (92,7-142,4)*<sup>&#8224;</sup></td>
                <td align="center">&lt;0,01</td>
              </tr>
              <tr>
                <td>
                  <bold>Volume sist&#243;lico do VE, mL</bold>
                </td>
                <td align="center">28,5 (23,7-34,2)</td>
                <td align="center">28,5 (23,3-34,7)</td>
                <td align="center">36,4 (30,5-59,2)*<sup>&#8224;</sup></td>
                <td align="center">&lt;0,01</td>
              </tr>
              <tr>
                <td>
                  <bold>Fra&#231;&#227;o de eje&#231;&#227;o do VE, %</bold>
                </td>
                <td align="center">67,9 (62,5-72,2)</td>
                <td align="center">68,2 (62,8-72,9)</td>
                <td align="center">63,5 (52,3-68,6)*<sup>&#8224;</sup></td>
                <td align="center">&lt;0,01</td>
              </tr>
              <tr>
                <td>
                  <bold>Volume do AE, mL</bold>
                </td>
                <td align="center">45 (36,6-54,1)</td>
                <td align="center">47,1 (38,3-58,3)</td>
                <td align="center">59,8 (43,8-76,6)*<sup>&#8224;</sup></td>
                <td align="center">&lt;0,01</td>
              </tr>
              <tr>
                <td>
                  <bold>&#205;ndice de volume do AE, mL/m<sup>2</sup></bold>
                </td>
                <td align="center">25,1 (20,8- 29,9)</td>
                <td align="center">27,2 (22,5- 32,6)</td>
                <td align="center">34,1 (25,8-45,5)*<sup>&#8224;</sup></td>
                <td align="center">&lt;0,01</td>
              </tr>
              <tr>
                <td>
                  <bold>Hipertens&#227;o pulmonar</bold>
                </td>
                <td align="center">25 (1,4)</td>
                <td align="center">291 (20,5)</td>
                <td align="center">18 (25,7)*</td>
                <td align="center">&lt;0,01</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN1">
              <p>Os valores s&#227;o apresentados como mediana e intervalo interquartil, ou n (%). O valor de p foi calculado pelo teste de Kruskal&#8211;Wallis (an&#225;lise p&#243;s-hoc usando o teste de Dunn) ou &#967;<sup>2</sup> (an&#225;lise p&#243;s-hoc usando o teste &#967;<sup>2</sup>), com corre&#231;&#227;o de Bonferroni para m&#250;ltiplas compara&#231;&#245;es quando o p global &lt; 0,05. \ *p &lt; 0,05 vs. sem DVC; <sup>&#8224;</sup>p &lt; 0,05 vs. DVC m&#237;nima/leve. DAC: doen&#231;a arterial coronariana; IMC: &#237;ndice de massa corporal; PAD: press&#227;o arterial diast&#243;lica; PAS: press&#227;o arterial sist&#243;lica; VE: ventr&#237;culo esquerdo; AE: &#225;trio esquerdo.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
      </p>
      <p>As an&#225;lises univariadas dos determinantes cl&#237;nicos e demogr&#225;ficos de RM, RA e RT moderadas/graves est&#227;o apresentadas nas <xref ref-type="sec" rid="suppl">Tabelas Suplementares</xref>. A <xref ref-type="table" rid="t2">Tabela 2</xref> resume os resultados das an&#225;lises de regress&#227;o log&#237;stica multivariada.</p>
      <p>
        <table-wrap id="t2">
          <label>Tabela 2</label>
          <caption>
            <title>&#8211; Determinantes cl&#237;nicos e demogr&#225;ficos da regurgita&#231;&#227;o valvar mitral, a&#243;rtica e tric&#250;spide moderada/grave</title>
          </caption>
          <table frame="hsides" rules="groups">
            <colgroup>
              <col/>
              <col/>
              <col/>
              <col/>
              <col/>
              <col/>
              <col/>
              <col/>
              <col/>
              <col/>
              <col/>
              <col/>
              <col/>
            </colgroup>
            <thead>
              <tr>
                <th align="left" rowspan="3">Covari&#225;veis</th>
                <th colspan="4">Regurgita&#231;&#227;o mitral</th>
                <th colspan="4">Regurgita&#231;&#227;o a&#243;rtica</th>
                <th colspan="4">Regurgita&#231;&#227;o tric&#250;spide</th>
              </tr>
              <tr>
                <th colspan="2">Modelo 1 (ajustado por idade/sexo)</th>
                <th colspan="2">Modelo 2*</th>
                <th colspan="2">Modelo 1 (ajustado por idade/sexo)</th>
                <th colspan="2">Modelo 2*</th>
                <th colspan="2">Modelo 1 (ajustado por idade/sexo)</th>
                <th colspan="2">Modelo 2*</th>
              </tr>
              <tr>
                <th>OR (IC95%)</th>
                <th>Valor p</th>
                <th>OR (IC95%)</th>
                <th>Valor p</th>
                <th>OR (IC95%)</th>
                <th>Valor p</th>
                <th>OR (IC95%)</th>
                <th>Valor p</th>
                <th>OR (IC95%)</th>
                <th>Valor p</th>
                <th>OR (IC95%)</th>
                <th>Valor p</th>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td>Idade (anos)</td>
                <td align="center">1,07 (1,02-1,13)</td>
                <td align="center">&lt;0,01</td>
                <td align="center">1,07 (1,01-1,13)</td>
                <td align="center">0,02</td>
                <td align="center">1,12 (1,04-1,20)</td>
                <td align="center">&lt;0,01</td>
                <td align="center">1,10 (1,03-1,19)</td>
                <td align="center">&lt;0,01</td>
                <td align="center">1,03 (0,96-1,09)</td>
                <td align="center">0,36</td>
                <td align="center">1,04 (0,97-1,11)</td>
                <td align="center">0,26</td>
              </tr>
              <tr>
                <td>Sexo masculino</td>
                <td align="center">0,83 (0,42-1,65)</td>
                <td align="center">0,61</td>
                <td align="center">0,80 (0,40-1,61)</td>
                <td align="center">0,54</td>
                <td align="center">1,18 (0,79-4,14)</td>
                <td align="center">0,15</td>
                <td align="center">1,82 (0,79-4,21)</td>
                <td align="center">0,16</td>
                <td align="center">0,15 (0,03-0,69)</td>
                <td align="center">0,01</td>
                <td align="center">0,18 (0,14-0,82)</td>
                <td align="center">0,02</td>
              </tr>
              <tr>
                <td>Ra&#231;a (preta)</td>
                <td> </td>
                <td> </td>
                <td align="center">3,28 (1,58-6,82)</td>
                <td align="center">&lt;0,01</td>
                <td> </td>
                <td> </td>
                <td align="center">2,41 (0,97-5,98)</td>
                <td align="center">0,06</td>
                <td> </td>
                <td> </td>
                <td align="center">3,70 (1,29-10,55)</td>
                <td align="center">0,01</td>
              </tr>
              <tr>
                <td>Tabagismo</td>
                <td> </td>
                <td> </td>
                <td align="center">1,23 (0,42-3,57)</td>
                <td align="center">0,70</td>
                <td> </td>
                <td> </td>
                <td align="center">1,29 (0,38-4,45)</td>
                <td align="center">0,68</td>
                <td> </td>
                <td> </td>
                <td align="center">0,69 (0,09-5,31)</td>
                <td align="center">0,72</td>
              </tr>
              <tr>
                <td>Obesidade</td>
                <td> </td>
                <td> </td>
                <td align="center">0,27 (0,08-0,89)</td>
                <td align="center">0,03</td>
                <td> </td>
                <td> </td>
                <td align="center">0,48 (0,41-1,62)</td>
                <td align="center">0,23</td>
                <td> </td>
                <td> </td>
                <td align="center">1,12 (0,35-3,58)</td>
                <td align="center">0,85</td>
              </tr>
              <tr>
                <td>Hipertens&#227;o</td>
                <td> </td>
                <td> </td>
                <td align="center">1,57 (0,71-3,49)</td>
                <td align="center">0,26</td>
                <td> </td>
                <td> </td>
                <td align="center">5,48 (1,59-18,9)</td>
                <td align="center">&lt;0,01</td>
                <td> </td>
                <td> </td>
                <td align="center">1,21 (0,41-3,53)</td>
                <td align="center">0,72</td>
              </tr>
              <tr>
                <td>Diabetes</td>
                <td> </td>
                <td> </td>
                <td align="center">1,49 (0,71-3,11)</td>
                <td align="center">0,29</td>
                <td> </td>
                <td> </td>
                <td align="center">0,34 (0,11-1,02)</td>
                <td align="center">0,06</td>
                <td> </td>
                <td> </td>
                <td align="center">0,16 (0,02-1,23)</td>
                <td align="center">0,08</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN2">
              <p>*Ajustado por idade, sexo, tabagismo, hipertens&#227;o e diabetes.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
      </p>
      <p>Na regress&#227;o log&#237;stica multivariada, RM moderada/grave foi independentemente associada &#224; idade mais avan&#231;ada, ra&#231;a preta e obesidade. RA moderada/grave esteve associada &#224; idade mais avan&#231;ada e hipertens&#227;o. RT moderada/grave foi associada ao sexo feminino e &#224; ra&#231;a preta (<xref ref-type="table" rid="t2">Tabela 2</xref>).</p>
      <p>Como esperado, o grupo com DVC moderada/grave apresentou maiores dimens&#245;es atriais e ventriculares esquerdas, maior massa ventricular esquerda, menor espessura relativa da parede e menor fra&#231;&#227;o de eje&#231;&#227;o do VE, al&#233;m de maior preval&#234;ncia de hipertens&#227;o pulmonar em compara&#231;&#227;o aos demais grupos (<xref ref-type="table" rid="t1">Tabela 1</xref>).</p>
      <p>Pequenas diferen&#231;as nos padr&#245;es de remodelamento foram identificadas entre os fen&#243;tipos de DVC moderada/grave mais prevalentes (RM, RA e RT), mesmo ap&#243;s ajuste por idade e sexo (<xref ref-type="sec" rid="suppl001">Material Suplementar &#8211; Figura 3</xref>).</p>
      <p>Ao todo, 355 participantes (10,9%) morreram durante um seguimento m&#233;dio de 4.260 &#177; 840 dias. Os participantes com DVC moderada/grave apresentaram pior sobrevida, conforme demonstrado na curva de Kaplan&#8211;Meier (log-rank p &lt; 0.001; <xref ref-type="fig" rid="f03">Figura 2</xref> e <xref ref-type="fig" rid="f01">Ilustra&#231;&#227;o Central</xref>). A DVC moderada/grave foi identificada como preditor independente de mortalidade (HR ajustado: 3,7; IC 95%: 2,17&#8211;6,31), ap&#243;s ajuste por idade, sexo e hipertens&#227;o.</p>
      <p>
        <fig id="f03">
          <label>Figura 2</label>
          <caption>
            <title>&#8211; Curvas de sobrevida de Kaplan&#8211;Meier dos participantes inclu&#237;dos no ELSA, de acordo com a gravidade da doen&#231;a valvar card&#237;aca (DVC).</title>
          </caption>
          <graphic xlink:href="1678-4170-abc-123-06-e20260060-60060-gf02.tif"/></fig>
      </p>
    </sec>
    <sec sec-type="discussion">
      <title>Discuss&#227;o</title>
      <p>Em uma popula&#231;&#227;o latino-americana de meia-idade, observamos que a DVC &#233; mais prevalente entre indiv&#237;duos mais velhos. Participantes com DVC moderada/grave apresentaram maior carga de fatores de risco cardiovascular, remodelamento card&#237;aco mais acentuado, menor fra&#231;&#227;o de eje&#231;&#227;o do VE e pior sobrevida em compara&#231;&#227;o &#224;queles sem doen&#231;a valvar significativa.</p>
      <p>Em nossa popula&#231;&#227;o, a preval&#234;ncia de DVC moderada/grave foi semelhante &#224; relatada em uma coorte hisp&#226;nica/latina dos Estados Unidos e em um estudo comunit&#225;rio recente envolvendo idosos assintom&#225;ticos.<sup><xref ref-type="bibr" rid="B1">1</xref>,<xref ref-type="bibr" rid="B3">3</xref></sup> De forma consistente com estudos anteriores, encontramos associa&#231;&#227;o independente entre idade e todos os tipos de regurgita&#231;&#227;o valvar moderada/grave.<sup><xref ref-type="bibr" rid="B1">1</xref>,<xref ref-type="bibr" rid="B5">5</xref>,<xref ref-type="bibr" rid="B13">13</xref></sup> No entanto, estudos com maior propor&#231;&#227;o de idosos relataram preval&#234;ncia mais elevada de DVC moderada/grave do que a observada em nossa coorte.<sup><xref ref-type="bibr" rid="B5">5</xref>,<xref ref-type="bibr" rid="B7">7</xref>,<xref ref-type="bibr" rid="B14">14</xref></sup> O estresse hemodin&#226;mico progressivo imposto &#224;s valvas ao longo dos anos provavelmente contribui para altera&#231;&#245;es degenerativas, sustentando o aumento da preval&#234;ncia de DVC com o avan&#231;ar da idade. Entre as diversas les&#245;es, a regurgita&#231;&#227;o mitral foi a mais frequente, em concord&#226;ncia com a maioria dos estudos populacionais previamente publicados.<sup><xref ref-type="bibr" rid="B1">1</xref>-<xref ref-type="bibr" rid="B3">3</xref>,<xref ref-type="bibr" rid="B7">7</xref></sup> A estenose a&#243;rtica tamb&#233;m &#233; uma doen&#231;a valvar altamente prevalente, mas sua frequ&#234;ncia aumenta substancialmente com o envelhecimento populacional.<sup><xref ref-type="bibr" rid="B5">5</xref>,<xref ref-type="bibr" rid="B15">15</xref>-<xref ref-type="bibr" rid="B19">19</xref></sup> Em nossa amostra, observamos maior preval&#234;ncia de regurgita&#231;&#227;o a&#243;rtica do que de estenose a&#243;rtica, possivelmente refletindo a idade m&#233;dia relativamente mais baixa da coorte (60 anos).</p>
      <p>A coorte ELSA-Brasil, que inclui participantes de seis estados distribu&#237;dos por tr&#234;s grandes regi&#245;es do pa&#237;s, captura a diversidade socioecon&#244;mica, racial e clim&#225;tica do Brasil. &#201; not&#225;vel que 44% de nossa amostra era composta por participantes n&#227;o brancos, e indiv&#237;duos que se autodeclararam pretos apresentaram maiores taxas de RM e RT moderadas/graves. N&#227;o foi poss&#237;vel determinar se fatores gen&#233;ticos, determinantes sociais ou diferen&#231;as no acesso &#224; sa&#250;de contribu&#237;ram para esses achados. Ainda assim, ao incluir um grupo populacional historicamente sub-representado em pesquisas, nosso estudo refor&#231;a a necessidade de investiga&#231;&#245;es mais amplas e inclusivas.</p>
      <p>Assim como em outros estudos, observamos que o grupo com DVC moderada/grave apresentou maior preval&#234;ncia de doen&#231;as cardiovasculares.<sup><xref ref-type="bibr" rid="B2">2</xref>,<xref ref-type="bibr" rid="B3">3</xref>,<xref ref-type="bibr" rid="B7">7</xref></sup> Notavelmente, a hipertens&#227;o foi independentemente associada &#224; regurgita&#231;&#227;o a&#243;rtica, em conson&#226;ncia com relatos que sugerem que a hipertens&#227;o pode predispor ao aumento da raiz a&#243;rtica e, consequentemente, &#224; regurgita&#231;&#227;o a&#243;rtica.<sup><xref ref-type="bibr" rid="B20">20</xref></sup></p>
      <p>Observamos c&#226;maras card&#237;acas maiores no grupo com DVC moderada/grave, consistentes com o remodelamento ventricular e atrial que ocorre em resposta &#224; sobrecarga hemodin&#226;mica imposta pela DVC. A maioria dos estudos anteriores tamb&#233;m relatou maiores dimens&#245;es atriais e ventriculares esquerdas, maior massa ventricular esquerda, menor fra&#231;&#227;o de eje&#231;&#227;o do VE e hipertens&#227;o pulmonar em participantes com DVC.<sup><xref ref-type="bibr" rid="B1">1</xref>,<xref ref-type="bibr" rid="B5">5</xref>,<xref ref-type="bibr" rid="B7">7</xref></sup> Esse fen&#243;tipo foi particularmente evidente na RM moderada/grave, o que pode refletir as consequ&#234;ncias da sobrecarga cr&#244;nica de volume e do aumento do estresse parietal sobre a estrutura e a fun&#231;&#227;o card&#237;acas.</p>
      <p>Fatores socioecon&#244;micos tamb&#233;m podem influenciar o cen&#225;rio da DVC, uma vez que atrasos e barreiras no acesso ao diagn&#243;stico, tratamento e preven&#231;&#227;o podem impactar de forma cr&#237;tica os desfechos da doen&#231;a. Em pa&#237;ses de renda m&#233;dia, como o Brasil, e em contextos sociais mais vulner&#225;veis, pode haver maior preval&#234;ncia de DVC e maior probabilidade de desfechos desfavor&#225;veis.</p>
      <p>Altera&#231;&#245;es estruturais e funcionais card&#237;acas associadas &#224; DVC podem contribuir para piores desfechos cl&#237;nicos e podem explicar a menor sobrevida observada nos participantes com DVC moderada/grave em nosso estudo, assim como em pesquisas anteriores.<sup><xref ref-type="bibr" rid="B5">5</xref>,<xref ref-type="bibr" rid="B21">21</xref></sup> Diante do envelhecimento populacional global e da forte associa&#231;&#227;o entre DVC moderada/grave e idade avan&#231;ada, compreender a progress&#227;o e a mortalidade associadas &#224; DVC torna-se cada vez mais importante.</p>
      <p>N&#227;o conseguimos identificar um padr&#227;o ecocardiogr&#225;fico espec&#237;fico t&#237;pico da doen&#231;a card&#237;aca reum&#225;tica nessa popula&#231;&#227;o de meia-idade. Em indiv&#237;duos mais jovens, a presen&#231;a de regurgita&#231;&#227;o valvar combinada ou doen&#231;a valvar mista &#233; um marcador importante de envolvimento reum&#225;tico e &#233; amplamente utilizada em programas de rastreamento em larga escala. No entanto, em popula&#231;&#245;es mais idosas, a especificidade desses achados &#233; limitada, pois etiologias degenerativas e funcionais tornam-se mais prevalentes e acabam predominando sobre os padr&#245;es reum&#225;ticos.<sup><xref ref-type="bibr" rid="B22">22</xref></sup></p>
      <p>Nosso estudo apresenta algumas limita&#231;&#245;es. A coorte foi composta por servidores p&#250;blicos de universidades e institui&#231;&#245;es de pesquisa, o que pode n&#227;o representar completamente a popula&#231;&#227;o brasileira geral. Por se tratar de uma coorte ocupacional, &#233; poss&#237;vel que indiv&#237;duos com doen&#231;as mais incapacitantes n&#227;o tenham sido inclu&#237;dos. A faixa et&#225;ria relativamente estreita, com a maioria dos participantes sendo de meia-idade, pode ter levado &#224; subestimativa de casos moderados a graves, e n&#227;o foi poss&#237;vel determinar a etiologia das principais DVC nativas. Al&#233;m disso, o delineamento transversal impede avaliar como a DVC influencia desfechos de longo prazo, incluindo sua contribui&#231;&#227;o direta para a mortalidade. Ademais, o estudo foi conduzido com base em um protocolo pr&#233;-definido, e as avalia&#231;&#245;es ecocardiogr&#225;ficas foram qualitativas, sem quantifica&#231;&#227;o detalhada de les&#245;es valvares espec&#237;ficas.</p>
      <p>Nesta coorte brasileira de meia-idade, a DVC mostrou-se prevalente e aumentou com o avan&#231;o da idade. Participantes com DVC moderada/grave apresentaram maior carga de comorbidades, remodelamento card&#237;aco mais acentuado, pior fun&#231;&#227;o sist&#243;lica e menor sobrevida. Compreender a DVC no contexto brasileiro atual pode contribuir para aprimorar o planejamento em sa&#250;de p&#250;blica e favorecer o diagn&#243;stico precoce e o manejo oportuno da doen&#231;a.</p>
    </sec>
    <sec id="suppl" sec-type="supplementary-material">
      <title>Material suplementar</title>
      <supplementary-material id="suppl01">
        <label>Supplementary material</label>
        <media mime-subtype="pdf" mimetype="application" xlink:href="https://minio.scielo.br/documentstore/1678-4170/x3gGf3xfXWcCqWZQQ7CxYHz/8739ebc0e09fdbd59f25339fa691d33af5f01879.pdf"/>
      </supplementary-material>
    </sec>
  </body>
  <back>
    <ack>
      <title>Agradecimentos</title>
      <p>Os autores gostariam de agradecer a todos os participantes do ELSA-Brasil por sua valiosa contribui&#231;&#227;o para este estudo.</p>
    </ack>
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    <fn-group>
      <fn fn-type="other">
        <label>Vincula&#231;&#227;o Acad&#234;mica:</label>
        <p> Este artigo &#233; parte de tese de Doutorado de Giulia Bevilacqua Schmitz pelo Programa de P&#243;s Gradua&#231;&#227;o em Cardiologia e Ci&#234;ncias Cardiovasculares- Faculdade de Medicina- Universidade Federal do Rio Grande do Sul.</p>
      </fn>
      <fn fn-type="other">
        <label>Aprova&#231;&#227;o &#201;tica e Consentimento Informado:</label>
        <p> Este estudo foi aprovado pelo Comit&#234; de &#201;tica do Hospital de Cl&#237;nicas de Porto Alegre sob o n&#250;mero de protocolo 0017.1.069.000-6,194/06. Todos os procedimentos envolvidos nesse estudo est&#227;o de acordo com a Declara&#231;&#227;o de Helsinki de 1975, atualizada em 2013. O consentimento informado foi obtido de todos os participantes inclu&#237;dos no estudo.</p>
      </fn>
      <fn fn-type="other">
        <label>Uso de Intelig&#234;ncia Artificial:</label>
        <p> Os autores n&#227;o utilizaram ferramentas de intelig&#234;ncia artificial no desenvolvimento deste trabalho.</p>
      </fn>
      <fn fn-type="data-availability" specific-use="data-available-upon-request">
        <label>Disponibilidade de Dados:</label>
        <p> Todo o conjunto de dados que d&#225; suporte aos resultados deste estudo est&#225; dispon&#237;vel mediante solicita&#231;&#227;o ao autor correspondente.</p>
      </fn>
      <fn fn-type="supplementary-material" id="supplfn">
        <label>*Material suplementar</label>
        <p> Para informa&#231;&#227;o adicional, por favor, <ext-link ext-link-type="uri" xlink:href="https://abccardiol.org/supplementary-material/2026/12306/2026_0060_supplementary_material.pdf"> clique aqui</ext-link>.</p>
      </fn>
      <fn fn-type="financial-disclosure">
        <label>Fontes de Financiamento:</label>
        <p> O presente estudo foi financiado pelo Minist&#233;rio da Sa&#250;de do Brasil (Departamento de Ci&#234;ncia e Tecnologia) e pelo Minist&#233;rio da Ci&#234;ncia, Tecnologia e Inova&#231;&#227;o (Financiadora de Estudos e Projetos &#8211; concess&#245;es 01 06 0010.00, 01 10 0643.00 RS, 01 06 0212.00 BA, 01 06 0300.00 ES, 01 06 0278.00 MG, 01 06 0115.00 SP, 01 06 0071.00 RJ), bem como pelo CNPq (Conselho Nacional de Desenvolvimento Cient&#237;fico e Tecnol&#243;gico).</p>
      </fn>
    </fn-group>
  </back>
  <sub-article article-type="translation" id="TRen" xml:lang="en">
    <front-stub>
      <article-id pub-id-type="doi">10.36660/abc.20260060i</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Original Article</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Epidemiology and Mortality of Valvular Heart Disease in Brazilian Adults: Findings from the ELSA-Brasil Cohort</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Schmitz</surname>
            <given-names>Guilia Bevilacqua</given-names>
          </name>
          <role>Conception and design of the research</role>
          <role>Acquisition of data</role>
          <role>Analysis and interpretation of the data and Statistical analysis</role>
          <role>Writing of the manuscript</role>
          <xref ref-type="aff" rid="aff1001">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Pianca</surname>
            <given-names>Eduardo Gatti</given-names>
          </name>
          <role>Critical revision of the manuscript for intellectual content</role>
          <xref ref-type="aff" rid="aff2001">
            <sup>2</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Nunes</surname>
            <given-names>Maria Do Carmo Pereira</given-names>
          </name>
          <role>Critical revision of the manuscript for intellectual content</role>
          <xref ref-type="aff" rid="aff3001">
            <sup>3</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Duncan</surname>
            <given-names>Bruce Bartholow</given-names>
          </name>
          <role>Critical revision of the manuscript for intellectual content</role>
          <xref ref-type="aff" rid="aff1001">
            <sup>1</sup>
          </xref>
          <xref ref-type="aff" rid="aff4001">
            <sup>4</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0003-2914-4406</contrib-id>
          <name>
            <surname>Foppa</surname>
            <given-names>Murilo</given-names>
          </name>
          <role>Conception and design of the research</role>
          <role>Acquisition of data</role>
          <role>Analysis and interpretation of the data and Statistical analysis</role>
          <role>Critical revision of the manuscript for intellectual content</role>
          <xref ref-type="aff" rid="aff1001">
            <sup>1</sup>
          </xref>
          <xref ref-type="aff" rid="aff2001">
            <sup>2</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0003-2493-0547</contrib-id>
          <name>
            <surname>Santos</surname>
            <given-names>Angela Barreto Santiago</given-names>
          </name>
          <role>Conception and design of the research</role>
          <role>Acquisition of data</role>
          <role>Analysis and interpretation of the data and Statistical analysis</role>
          <role>Writing of the manuscript</role>
          <xref ref-type="aff" rid="aff1001">
            <sup>1</sup>
          </xref>
          <xref ref-type="aff" rid="aff2001">
            <sup>2</sup>
          </xref>
        </contrib>
      </contrib-group>
      <aff id="aff1001">
        <label>1</label>
        <country country="BR">Brazil</country>
        <institution content-type="original">P&#243;s-Gradua&#231;&#227;o em Cardiologia e Ci&#234;ncias Cardiovasculares &#8211; Faculdade de Medicina &#8211; Universidade Federal do Rio Grande do Sul, Porto Alegre, RS &#8211; Brazil</institution>
      </aff>
      <aff id="aff2001">
        <label>2</label>
        <country country="BR">Brazil</country>
        <institution content-type="original">Servi&#231;o de Cardiologia, Hospital de Cl&#237;nicas de Porto Alegre, Porto Alegre, RS &#8211; Brazil</institution>
      </aff>
      <aff id="aff3001">
        <label>3</label>
        <country country="BR">Brazil</country>
        <institution content-type="original">Faculdade de Medicina, Hospital das Cl&#237;nicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG &#8211; Brazil</institution>
      </aff>
      <aff id="aff4001">
        <label>4</label>
        <country country="BR">Brazil</country>
        <institution content-type="original">P&#243;s-Gradua&#231;&#227;o em Epidemiologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS &#8211; Brazil</institution>
      </aff>
      <author-notes>
        <corresp id="c01001"><label>Mailing Address:</label> Angela Barreto Santiago Santos Hospital de Clinicas de Porto Alegre &#8211; Cardiologia - Rua Ramiro Barcelos, 2350, Sala 2061. Postal Code 90035-903, Porto Alegre, RS &#8211; Brazil E-mail: abssantos@hcpa.edu.br </corresp>
        <fn fn-type="coi-statement">
          <label>Potential Conflict of Interest:</label>
          <p>No potential conflict of interest relevant to this article was reported.</p>
        </fn>
        <fn fn-type="edited-by">
          <label>Editor responsible for the review:</label>
          <p> Ana Teresa Tim&#243;teo</p>
        </fn>
      </author-notes>
      <abstract>
        <title>Abstract</title>
        <sec>
          <title>Background</title>
          <p> Most of the current evidence on valvular heart disease (VHD) comes from high-income countries. Access to treatment and the impact of VHD on quality of life may vary substantially across nations, largely due to socioeconomic differences.</p>
        </sec>
        <sec>
          <title>Objective</title>
          <p> This study aimed to estimate the burden of VHD and its association with mortality in a middle-income country.</p>
        </sec>
        <sec>
          <title>Methods</title>
          <p> We included participants from the ELSA-Brasil cohort who underwent transthoracic echocardiography at baseline (3,267 participants; 1,539 males; mean age 60.6 &#177; 8.8 years) across six Brazilian states. Participants were categorized into three groups&#8212;no VHD, trace/mild VHD, and moderate/severe VHD&#8212;and their characteristics and associated factors were analyzed. P-values &lt; 0.05 were considered statistically significant.</p>
        </sec>
        <sec>
          <title>Results</title>
          <p> Among all participants, 2.4% had moderate/severe VHD (including 7 participants with prosthetic valves), and 43.6% had trace/mild VHD. The most prevalent moderate/severe VHD was mitral regurgitation, followed by aortic and tricuspid regurgitation, with 56 participants (86%) presenting isolated valvular regurgitation. Moderate/severe VHD was more common in older individuals and was associated with a higher prevalence of most cardiovascular comorbidities, but with lower obesity rates. It was also associated with greater cardiac remodeling and reduced systolic function, with phenotypic variations depending on the affected valve. Moderate/severe VHD was linked to increased 10-year mortality (HR: 3.7; 95% CI [2.17&#8211;6.31]), independent of age, sex, and hypertension.</p>
        </sec>
        <sec>
          <title>Conclusion</title>
          <p> VHD is common among community-dwelling adults in this middle-income country and increases with age. Participants with moderate/severe VHD exhibited a greater burden of comorbidities, more pronounced cardiac remodeling, worse systolic function, and substantially reduced long-term survival.</p>
        </sec>
      </abstract>
      <abstract abstract-type="graphical">
        <p>
          <fig id="f01001">
            <label>Central Illustration:</label>
            <caption>
              <title>Epidemiology and Mortality of Valvular Heart Disease in Brazilian Adults: Findings from the ELSA-Brasil Cohort</title>
            </caption>
            <graphic xlink:href="1678-4170-abc-123-06-e20260060-60060-gf01-en.tif"/></fig>
        </p>
      </abstract>
      <kwd-group xml:lang="en">
        <title>Keywords:</title>
        <kwd>Heart Valve Diseases</kwd>
        <kwd>Epidemiology</kwd>
        <kwd>Mortality</kwd>
        <kwd>Adult</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <sec sec-type="intro">
        <title>Introduction</title>
        <p>Valvular heart disease (VHD) is a prevalent cardiac condition associated with increased morbidity and mortality,<sup><xref ref-type="bibr" rid="B1">1</xref>-<xref ref-type="bibr" rid="B3">3</xref></sup> and its prevalence rises with age.<sup><xref ref-type="bibr" rid="B4">4</xref>-<xref ref-type="bibr" rid="B6">6</xref></sup> Although most patients have mild and asymptomatic VHD, those with moderate or severe disease may experience significant complications, including heart failure and death.<sup><xref ref-type="bibr" rid="B2">2</xref>,<xref ref-type="bibr" rid="B3">3</xref></sup> Moreover, the impact of VHD on quality of life and access to treatment varies according to the socioeconomic context of each country.</p>
        <p>Several factors have been previously associated with different types of VHD. Mitral regurgitation is linked to older age, female sex, hypertension, reduced left ventricular (LV) ejection fraction (EF), and lower body mass index (BMI).<sup><xref ref-type="bibr" rid="B2">2</xref>,<xref ref-type="bibr" rid="B5">5</xref>,<xref ref-type="bibr" rid="B7">7</xref></sup> Tricuspid regurgitation may be associated with older age, female sex, lower BMI, alcohol consumption, higher HDL-cholesterol, increased heart rate, LV dysfunction, left-sided heart disease, and left atrial enlargement.<sup><xref ref-type="bibr" rid="B6">6</xref>-<xref ref-type="bibr" rid="B8">8</xref></sup> Aortic regurgitation is primarily associated with older age, male sex, higher systolic blood pressure, aortic root dilation, and increased LV mass index.</p>
        <p>Most available VHD data originates from high-income countries, and population-based evidence from Latin America remains scarce, limiting accurate estimates of the VHD burden in this region. The ELSA-Brasil cohort provides a unique opportunity to obtain reliable estimates of the prevalence and outcomes of VHD and to assess the impact of the ongoing epidemiologic transition in a middle-income country. Therefore, the present study aimed to investigate: 1) the prevalence of VHD in a free-living Brazilian adult population; 2) the clinical and demographic determinants of VHD; 3) the echocardiographic phenotype of each moderate/severe VHD; and 4) the impact of moderate/severe VHD on long-term mortality.</p>
      </sec>
      <sec sec-type="materials|methods">
        <title>Material and Methods</title>
        <sec>
          <title>Study population</title>
          <p>The Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) is a prospective epidemiological study designed to investigate cardiovascular disease and diabetes in 15,105 male and female civil servants from universities or research institutions located in six Brazilian cities (S&#227;o Paulo, Rio de Janeiro, Belo Horizonte, Vit&#243;ria, Salvador, and Porto Alegre). All active or retired employees aged 35 to 74 years were eligible for participation. The study details &#8211; including design, eligibility criteria, recruitment, and assessments &#8211; have been described elsewhere.<sup><xref ref-type="bibr" rid="B9">9</xref>,<xref ref-type="bibr" rid="B10">10</xref></sup></p>
          <p>A cohort random subsample was defined <italic>a priori</italic> for case-cohort analyses. This random sample (n = 1,543) consisted of 10% of the total cohort, selected using the same stratification criteria applied to the full sample (sex, age group, and occupational category). A computer-generated random number was assigned to each participant, and the 10% lowest numbers within each stratum were selected. From this random sample, transthoracic echocardiograms (TTE) were obtained during the first study visit in 1,172 participants.</p>
          <p>For the present analysis, we included all cohort participants who underwent baseline TTE (August 2008 to December 2010), prioritizing all individuals aged 60 years or older (N = 2,095), as well as the predefined random subsample comprising 10% of the entire cohort (N = 1,172) (<xref ref-type="sec" rid="suppl001">Supplemental Material &#8211; Figure 1</xref>).</p>
          <p>All-cause mortality data up to December 2022 were collected through annual telephone follow-up and confirmed by medical chart review, death certificates, and linkage to national databases such as the National Mortality System.</p>
          <p>The ELSA-Brasil study complies with the principles of the Declaration of Helsinki and was approved by the research and ethics committees of the participating institutions. All participants provided written informed consent.</p>
        </sec>
        <sec>
          <title>Echocardiography</title>
          <p>All transthoracic echocardiograms were obtained during the first study visit. Images were acquired using identically configured echocardiography machines (Aplio XG, Toshiba, Japan) equipped with a 2.5-MHz sector transducer, following standardized protocols. Examinations were recorded in digital format and transferred to the ELSA-Brasil Echocardiography Reading Center in Porto Alegre, Brazil. Standard echocardiographic and Doppler parameters were analyzed using an offline workstation (ComPACS 10.5; Medimatic SrL, Italy). All measurements were performed in triplicate according to the recommendations of the American Society of Echocardiography<sup><xref ref-type="bibr" rid="B1">1</xref><xref ref-type="bibr" rid="B1">1</xref></sup> and included LV diameters and volumes, LV wall thickness, LV mass, LV ejection fraction, and left atrial (LA) volume and diameter.</p>
          <p>VHD severity was initially flagged by the trained echocardiographer during image acquisition, and additional images beyond the pre-acquisition protocol were obtained at the sonographer&#8217;s discretion to better characterize VHD, including assessment of mitral valve prolapse and bicuspid aortic valve morphology. All images were subsequently reviewed at the reading center (regardless of initial flagging) and qualitatively assessed using color Doppler and spectral Doppler findings, following criteria applied in previous population-based studies.<sup><xref ref-type="bibr" rid="B12">12</xref></sup></p>
          <p>Additionally, the definition of aortic stenosis (AS) was based on the antegrade systolic velocity across the aortic valve, while the classification of mitral stenosis (MS) was based on the mean transmitral gradient.</p>
          <p>The study protocol specifically aimed to identify mitral valve prolapse, defined as maximal leaflet thickness &gt;5 mm and systolic displacement &gt;2 mm beyond the annular plane in the parasternal view, as well as bicuspid aortic valve morphology, characterized by eccentric leaflet coaptation, the presence of two leaflets during systole, and an elliptical systolic orifice. Pulmonary hypertension was defined as a right atrial&#8211;right ventricular (RA&#8211;RV) gradient &gt;25 mmHg.</p>
        </sec>
        <sec>
          <title>Statistical analysis</title>
          <p>We categorized participants into three groups: no VHD, trace/mild VHD, and moderate/severe VHD. Continuous variables are presented as median and interquartile range and were compared using the Kruskal&#8211;Wallis test. When the global p-value was &lt;0.05, post hoc pairwise comparisons were performed using Dunn&#8217;s test with Bonferroni correction for multiple comparisons. Categorical variables are presented as counts and proportions and were compared using Fisher&#8217;s exact test, followed by pairwise Fisher&#8217;s exact tests when the global p-value was &lt;0.05, with p-values adjusted using the Bonferroni method.</p>
          <p>Each valvular heart disease was analyzed across age decades using Cuzick&#8217;s non-parametric test for trend (nptrend). Relevant correlates of the most prevalent moderate/severe VHD &#8211; mitral regurgitation (MR), aortic regurgitation (AR), and tricuspid regurgitation (TR) &#8211; were first explored in univariate analyses, followed by multivariable logistic regression models including covariates selected a priori based on established literature, representing clinically distinct risk factors for valvular disease (age, sex, Black race category, smoking, obesity, hypertension, and diabetes). Additionally, we evaluated the main echocardiographic parameters associated with specific VHD phenotypes (LV end-diastolic volume, LV end-systolic volume, LV relative wall thickness, LV mass, LV ejection fraction, LA volume index, and pulmonary hypertension) using logistic regression models adjusted for age and sex.</p>
          <p>Cumulative survival was estimated using the Kaplan&#8211;Meier method, and survival curves were compared using the log-rank test. Participants with prosthetic valves were included in the overall prevalence of moderate/severe VHD but were excluded from subsequent characterization analyses due to alterations in the natural history of VHD.</p>
          <p>All statistical analyses were performed using the STATA software package (version 12; StataCorp, College Station, Texas). All tests were two-sided, and p-values &lt;0.05 were considered statistically significant.</p>
        </sec>
      </sec>
      <sec sec-type="results">
        <title>Results</title>
        <p>Our sample consisted of 3,267 participants (1,539 males; mean age 60.6 &#177; 8.8 years; 56% self-reported as White) from six different states in Brazil (15% from the Northeast, 63% from the Southeast, and 22% from the South). The prevalence of hypertension was 51.0%, diabetes 23.4%, overweight 42.8%, obesity 22.2%, coronary artery disease 6.5%, and smoking 10.2% in the overall population.</p>
        <p>Among all participants, 2.4% had moderate/severe VHD (including 7 participants with prosthetic valves), and 43.6% had trace/mild VHD (<xref ref-type="fig" rid="f02001">Figure 1</xref> and <xref ref-type="fig" rid="f01001">Central Illustration</xref>). The most prevalent moderate/severe VHD was mitral regurgitation, followed by aortic and tricuspid regurgitation. Among those with moderate/severe VHD, 56 (86%) had isolated valvular regurgitation; 8 (12.5%) had mixed disease involving two regurgitant valves; and 1 (1.5%) had mixed disease involving three regurgitant valves. Moderate/severe stenosis was present in 6 participants (8.5% of those with moderate/severe VHD). Additionally, the prevalence of mitral valve prolapse was 1.2%, and bicuspid aortic valve was 0.5%, with no significant differences between sexes.</p>
        <p>
          <fig id="f02001">
            <label>Figure 1</label>
            <caption>
              <title>&#8211; Prevalence of valvular heart disease (VHD) in the sample.</title>
            </caption>
            <graphic xlink:href="1678-4170-abc-123-06-e20260060-60060-gf02-en.tif"/></fig>
        </p>
        <p>Participants older than 55 years had a higher prevalence of both trace/mild and moderate/severe VHD compared with younger individuals. Only four cases of moderate/severe VHD were identified among participants younger than 55 years, corresponding to a prevalence below 1% (<xref ref-type="sec" rid="suppl001">Supplemental Material &#8211; Table 1</xref>).</p>
        <p>Participants with moderate/severe VHD were older and had a higher prevalence of hypertension, coronary artery disease, heart failure, smoking, and atrial flutter/fibrillation, as well as a lower prevalence of obesity and metabolic syndrome (<xref ref-type="table" rid="t1001">Table 1</xref>).</p>
        <p>
          <table-wrap id="t1001">
            <label>Table 1</label>
            <caption>
              <title>&#8211; Baseline demographic characteristics and echocardiographic parameters of ELSA-Brasil participants who underwent echocardiography at baseline, stratified by valvular heart disease severity</title>
            </caption>
            <table frame="hsides" rules="groups">
              <colgroup>
                <col/>
                <col/>
                <col/>
                <col/>
                <col/>
              </colgroup>
              <thead>
                <tr>
                  <th align="left" style="font-weight:normal"> </th>
                  <th style="font-weight:normal"> No VHD (n=1,770) </th>
                  <th>Trace/Mild VHD(n=1,420)</th>
                  <th>Mod/severe VHD (n=70)</th>
                  <th>p-value</th>
                </tr>
              </thead>
              <tbody>
                <tr>
                  <td>
                    <bold>Age years</bold>
                  </td>
                  <td align="center">61 (51&#8211;65)</td>
                  <td align="center">64 (60-68)</td>
                  <td align="center">65 (61-71)*<sup>&#8224;</sup></td>
                  <td align="center">&lt;0.01</td>
                </tr>
                <tr>
                  <td>
                    <bold>Sex</bold>
                  </td>
                  <td> </td>
                  <td> </td>
                  <td> </td>
                  <td> </td>
                </tr>
                <tr>
                  <td>Female</td>
                  <td align="center">909 (51.3)</td>
                  <td align="center">779 (54.9)</td>
                  <td align="center">38 (54.3)</td>
                  <td align="center">0.13</td>
                </tr>
                <tr>
                  <td>Male</td>
                  <td align="center">861(48.6)</td>
                  <td align="center">641 (45.14)</td>
                  <td align="center">32 (45.7)</td>
                  <td align="center">0.13</td>
                </tr>
                <tr>
                  <td>
                    <bold>Self-identified skin color/ race category</bold>
                  </td>
                  <td> </td>
                  <td> </td>
                  <td> </td>
                  <td align="center">0.005</td>
                </tr>
                <tr>
                  <td>White</td>
                  <td align="center">993 (55.0)</td>
                  <td align="center">783 (43.4)</td>
                  <td align="center">29 (1.6)</td>
                  <td> </td>
                </tr>
                <tr>
                  <td>Black</td>
                  <td align="center">243 (48.9)</td>
                  <td align="center">231 (46.6)</td>
                  <td align="center">22 (4.4)</td>
                  <td> </td>
                </tr>
                <tr>
                  <td>Brown (&#8216;pardo&#8217;)</td>
                  <td align="center">442 (55.0)</td>
                  <td align="center">346 (43.0)</td>
                  <td align="center">16 (2.0)</td>
                  <td> </td>
                </tr>
                <tr>
                  <td>Asian</td>
                  <td align="center">44 (55.0)</td>
                  <td align="center">35 (43.8)</td>
                  <td align="center">1 (1.2)</td>
                  <td> </td>
                </tr>
                <tr>
                  <td>Indigenous</td>
                  <td align="center">26 (68.4)</td>
                  <td align="center">11 (29.0)</td>
                  <td align="center">1 (2.6)</td>
                  <td> </td>
                </tr>
                <tr>
                  <td>
                    <bold>Brazilian centers</bold>
                  </td>
                  <td> </td>
                  <td> </td>
                  <td> </td>
                  <td align="center">&lt;0.01</td>
                </tr>
                <tr>
                  <td>Bahia</td>
                  <td align="center">218(44.1)</td>
                  <td align="center">261(52.8)</td>
                  <td align="center">15 (3.1)</td>
                  <td> </td>
                </tr>
                <tr>
                  <td>Esp&#237;rito Santo</td>
                  <td align="center">158(56.4)</td>
                  <td align="center">119(42.5)</td>
                  <td align="center">2 (1.1)</td>
                  <td> </td>
                </tr>
                <tr>
                  <td>Minas Gerais</td>
                  <td align="center">390(47.5)</td>
                  <td align="center">411(50.1)</td>
                  <td align="center">20 (2.4)</td>
                  <td> </td>
                </tr>
                <tr>
                  <td>Rio de Janeiro</td>
                  <td align="center">238(75.8)</td>
                  <td align="center">73(23.2)</td>
                  <td align="center">3 (1.0)</td>
                  <td> </td>
                </tr>
                <tr>
                  <td>S&#227;o Paulo</td>
                  <td align="center">377(58.9)</td>
                  <td align="center">246(38.4)</td>
                  <td align="center">17 (2.7)</td>
                  <td> </td>
                </tr>
                <tr>
                  <td>Rio Grande do Sul</td>
                  <td align="center">389(54.7)</td>
                  <td align="center">310(43.6)</td>
                  <td align="center">12 (1.7)</td>
                  <td> </td>
                </tr>
                <tr>
                  <td>
                    <bold>SBP (mmHg)</bold>
                  </td>
                  <td align="center">122.5 (112.5-134)</td>
                  <td align="center">125 (114-139)</td>
                  <td align="center">132 (118-142)*</td>
                  <td align="center">&lt;0.01</td>
                </tr>
                <tr>
                  <td>
                    <bold>DBP (mmHg)</bold>
                  </td>
                  <td align="center">76 (69.5-83)</td>
                  <td align="center">75.5 (69-82.5)</td>
                  <td align="center">71.8 (65.5-80)*<sup>&#8224;</sup></td>
                  <td align="center">&lt;0.01</td>
                </tr>
                <tr>
                  <td>
                    <bold>BMI (Kg/m<sup>2</sup>)</bold>
                  </td>
                  <td align="center">26.9 (24.3-29.9)</td>
                  <td align="center">26 (23.6-28.9)</td>
                  <td align="center">25.4 (23.3-28.3)*</td>
                  <td align="center">&lt;0.01</td>
                </tr>
                <tr>
                  <td>
                    <bold>Overweight</bold>
                  </td>
                  <td align="center">769 (43.5)</td>
                  <td align="center">597 (42)</td>
                  <td align="center">28 (40)</td>
                  <td align="center">0.66</td>
                </tr>
                <tr>
                  <td>
                    <bold>Obesity</bold>
                  </td>
                  <td align="center">437 (24.7)</td>
                  <td align="center">275 (19.4)</td>
                  <td align="center">10 (14.3)*</td>
                  <td align="center">&lt;0.01</td>
                </tr>
                <tr>
                  <td>
                    <bold>Hypertension</bold>
                  </td>
                  <td align="center">852 (48.2)</td>
                  <td align="center">760 (53.6)</td>
                  <td align="center">49 (70)*<sup>&#8224;</sup></td>
                  <td align="center">&lt;0.01</td>
                </tr>
                <tr>
                  <td>
                    <bold>Diabetes</bold>
                  </td>
                  <td align="center">408 (23.1)</td>
                  <td align="center">338 (23.8)</td>
                  <td align="center">15 (21.4)</td>
                  <td align="center">0.85</td>
                </tr>
                <tr>
                  <td>
                    <bold>Metabolic Syndrome</bold>
                  </td>
                  <td align="center">944 (53.6)</td>
                  <td align="center">710 (50.1)</td>
                  <td align="center">29 (41.4)</td>
                  <td align="center">0.03</td>
                </tr>
                <tr>
                  <td>
                    <bold>Stroke</bold>
                  </td>
                  <td align="center">33 (1.9)</td>
                  <td align="center">29 (2.0)</td>
                  <td align="center">3 (4.3)</td>
                  <td align="center">0.27</td>
                </tr>
                <tr>
                  <td>
                    <bold>CHD</bold>
                  </td>
                  <td align="center">94 (5.5)</td>
                  <td align="center">101 (7.3)</td>
                  <td align="center">12 (17.4)*<sup>&#8224;</sup></td>
                  <td align="center">&lt;0.01</td>
                </tr>
                <tr>
                  <td>
                    <bold>Heart failure</bold>
                  </td>
                  <td align="center">36 (2)</td>
                  <td align="center">51 (3.6)</td>
                  <td align="center">14 (20)*<sup>&#8224;</sup></td>
                  <td align="center">&lt;0.01</td>
                </tr>
                <tr>
                  <td>
                    <bold>Smoking</bold>
                  </td>
                  <td align="center">220 (12.4)</td>
                  <td align="center">107 (7.5)</td>
                  <td align="center">6 (8.6)</td>
                  <td align="center">&lt;0.01</td>
                </tr>
                <tr>
                  <td>
                    <bold>AF and/or flutter</bold>
                  </td>
                  <td align="center">6 (0.3)</td>
                  <td align="center">17 (1.2)</td>
                  <td align="center">4 (5.7)*<sup>&#8224;</sup></td>
                  <td align="center">&lt;0.01</td>
                </tr>
                <tr>
                  <td>
                    <bold>LV diastolic diameter, mm</bold>
                  </td>
                  <td align="center">45 (42-48)</td>
                  <td align="center">45 (41-48)</td>
                  <td align="center">50 (45-56)*<sup>&#8224;</sup></td>
                  <td align="center">&lt;0.01</td>
                </tr>
                <tr>
                  <td>
                    <bold>LV systolic diameter, mm</bold>
                  </td>
                  <td align="center">28 (25-30)</td>
                  <td align="center">28 (25-31)</td>
                  <td align="center">31 (29-40)*<sup>&#8224;</sup></td>
                  <td align="center">&lt;0.01</td>
                </tr>
                <tr>
                  <td>
                    <bold>Septum thickness, mm</bold>
                  </td>
                  <td align="center">10 (9-11)</td>
                  <td align="center">10 (9-11)</td>
                  <td align="center">10 (9-12)*</td>
                  <td align="center">&lt;0.01</td>
                </tr>
                <tr>
                  <td>
                    <bold>Posterior wall thickness, mm</bold>
                  </td>
                  <td align="center">9 (8-10)</td>
                  <td align="center">9 (8-10)</td>
                  <td align="center">9 (8-10)</td>
                  <td align="center">0.5</td>
                </tr>
                <tr>
                  <td>
                    <bold>LV Relative Wall Thickness</bold>
                  </td>
                  <td align="center">0.42 (0.38-0.47)</td>
                  <td align="center">0.42 (0.38-0.48)</td>
                  <td align="center">0.38 (0.34-0.44)*<sup>&#8224;</sup></td>
                  <td align="center">&lt;0.01</td>
                </tr>
                <tr>
                  <td>
                    <bold>LV mass, g</bold>
                  </td>
                  <td align="center">138.7 (114.7-167.5)</td>
                  <td align="center">140 (116.8-170.8)</td>
                  <td align="center">177.8 (131.6-242.2)*<sup>&#8224;</sup></td>
                  <td align="center">&lt;0.01</td>
                </tr>
                <tr>
                  <td>
                    <bold>LV diastolic volume, mL</bold>
                  </td>
                  <td align="center">89.1 (77.9-101.6)</td>
                  <td align="center">89.3 (77.3-103.9)</td>
                  <td align="center">112.1 (92.7-142.4)*<sup>&#8224;</sup></td>
                  <td align="center">&lt;0.01</td>
                </tr>
                <tr>
                  <td>
                    <bold>LV systolic volume, mL</bold>
                  </td>
                  <td align="center">28.5 (23.7-34.2)</td>
                  <td align="center">28.5 (23.3-34.7)</td>
                  <td align="center">36.4 (30.5-59.2)*<sup>&#8224;</sup></td>
                  <td align="center">&lt;0.01</td>
                </tr>
                <tr>
                  <td>
                    <bold>LV ejection fraction, %</bold>
                  </td>
                  <td align="center">67.9 (62.5-72.2)</td>
                  <td align="center">68.2 (62.8-72.9)</td>
                  <td align="center">63.5 (52.3-68.6)*<sup>&#8224;</sup></td>
                  <td align="center">&lt;0.01</td>
                </tr>
                <tr>
                  <td>
                    <bold>LA volume, mL</bold>
                  </td>
                  <td align="center">45 (36.6-54.1)</td>
                  <td align="center">47.1 (38.3-58.3)</td>
                  <td align="center">59.8 (43.8-76.6)*<sup>&#8224;</sup></td>
                  <td align="center">&lt;0.01</td>
                </tr>
                <tr>
                  <td>
                    <bold>LA volume index, mL/m<sup>2</sup></bold>
                  </td>
                  <td align="center">25.1 (20.8- 29.9)</td>
                  <td align="center">27.2 (22.5- 32.6)</td>
                  <td align="center">34.1 (25.8-45.5)*<sup>&#8224;</sup></td>
                  <td align="center">&lt;0.01</td>
                </tr>
                <tr>
                  <td>
                    <bold>Pulmonary hypertension</bold>
                  </td>
                  <td align="center">25 (1.4)</td>
                  <td align="center">291 (20.5)</td>
                  <td align="center">18 (25.7)*</td>
                  <td align="center">&lt;0.01</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN1001">
                <p>Values are shown as median and interquartile range, or n (%). p-value was calculated by Kruskal-Wallis test (post hoc analysis using Dunn&#8217;s test) or &#967;<sup>2</sup> (post hoc analysis using &#967;<sup>2</sup> test) with Bonferroni correction for multiple comparisons if p global &lt;0.05. *p &lt; 0.05 vs. no VHD, <sup>&#8224;</sup>p &lt; 0.05 vs. Trace/Mild VHD. CHD: coronary heart disease; AF: atrial fibrillation; BMI: body-mass index; DBP: diastolic blood pressure; SBP: systolic blood pressure; LV: left ventricle; LA: left atrial.</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
        </p>
        <p>Univariable analyses of the clinical and demographic determinants of moderate/severe MR, AR, and TR are presented in the <xref ref-type="sec" rid="suppl001">Supplemental Tables</xref>. <xref ref-type="table" rid="t2001">Table 2</xref> summarizes the results of the multivariable logistic regression analyses.</p>
        <p>
          <table-wrap id="t2001">
            <label>Table 2</label>
            <caption>
              <title>&#8211; Clinical and demographic determinants of moderate/severe mitral, aortic, and tricuspid valvular regurgitations</title>
            </caption>
            <table frame="hsides" rules="groups">
              <colgroup>
                <col/>
                <col/>
                <col/>
                <col/>
                <col/>
                <col/>
                <col/>
                <col/>
                <col/>
                <col/>
                <col/>
                <col/>
                <col/>
              </colgroup>
              <thead>
                <tr>
                  <th align="left" rowspan="3">Covariates</th>
                  <th colspan="4">Mitral regurgitation</th>
                  <th colspan="4">Aortic regurgitation</th>
                  <th colspan="4">Tricuspid regurgitation</th>
                </tr>
                <tr>
                  <th colspan="2">Model 1 (Adjusted by age/sex)</th>
                  <th colspan="2">Model 2*</th>
                  <th colspan="2">Model 1 (Adjusted by age/sex)</th>
                  <th colspan="2">Model 2*</th>
                  <th colspan="2">Model 1 (Adjusted by age/sex)</th>
                  <th colspan="2">Model 2*</th>
                </tr>
                <tr>
                  <th>OR (95% CI)</th>
                  <th>p value</th>
                  <th>OR (95% CI)</th>
                  <th>p value</th>
                  <th>OR (95% CI)</th>
                  <th>p value</th>
                  <th>OR (95% CI)</th>
                  <th>p value</th>
                  <th>OR (95% CI)</th>
                  <th>p value</th>
                  <th>OR (95% CI)</th>
                  <th>p value</th>
                </tr>
              </thead>
              <tbody>
                <tr>
                  <td>Age (years)</td>
                  <td align="center">1.07 (1.02-1.13)</td>
                  <td align="center">&lt;0.01</td>
                  <td align="center">1.07 (1.01-1.13)</td>
                  <td align="center">0.02</td>
                  <td align="center">1.12 (1.04-1.20)</td>
                  <td align="center">&lt;0.01</td>
                  <td align="center">1.10 (1.03-1.19)</td>
                  <td align="center">&lt;0.01</td>
                  <td align="center">1.03 (0.96-1.09)</td>
                  <td align="center">0.36</td>
                  <td align="center">1.04 (0.97-1.11)</td>
                  <td align="center">0.26</td>
                </tr>
                <tr>
                  <td>Male sex</td>
                  <td align="center">0.83 (0.42-1.65)</td>
                  <td align="center">0.61</td>
                  <td align="center">0.80 (0.40-1.61)</td>
                  <td align="center">0.54</td>
                  <td align="center">1.18 (0.79-4.14)</td>
                  <td align="center">0.15</td>
                  <td align="center">1.82 (0.79-4.21)</td>
                  <td align="center">0.16</td>
                  <td align="center">0.15 (0.03-0.69)</td>
                  <td align="center">0.01</td>
                  <td align="center">0.18 (0.14-0.82)</td>
                  <td align="center">0.02</td>
                </tr>
                <tr>
                  <td>Race (Black)</td>
                  <td> </td>
                  <td> </td>
                  <td align="center">3.28 (1.58-6.82)</td>
                  <td align="center">&lt;0.01</td>
                  <td> </td>
                  <td> </td>
                  <td align="center">2.41 (0.97-5.98)</td>
                  <td align="center">0.06</td>
                  <td> </td>
                  <td> </td>
                  <td align="center">3.70 (1.29-10.55)</td>
                  <td align="center">0.01</td>
                </tr>
                <tr>
                  <td>Smoking</td>
                  <td> </td>
                  <td> </td>
                  <td align="center">1.23 (0.42-3.57)</td>
                  <td align="center">0.70</td>
                  <td> </td>
                  <td> </td>
                  <td align="center">1.29 (0.38-4.45)</td>
                  <td align="center">0.68</td>
                  <td> </td>
                  <td> </td>
                  <td align="center">0.69 (0.09-5.31)</td>
                  <td align="center">0.72</td>
                </tr>
                <tr>
                  <td>Obesity</td>
                  <td> </td>
                  <td> </td>
                  <td align="center">0.27 (0.08-0.89)</td>
                  <td align="center">0.03</td>
                  <td> </td>
                  <td> </td>
                  <td align="center">0.48 (0.41-1.62)</td>
                  <td align="center">0.23</td>
                  <td> </td>
                  <td> </td>
                  <td align="center">1.12 (0.35-3.58)</td>
                  <td align="center">0.85</td>
                </tr>
                <tr>
                  <td>Hypertension</td>
                  <td> </td>
                  <td> </td>
                  <td align="center">1.57 (0.71-3.49)</td>
                  <td align="center">0.26</td>
                  <td> </td>
                  <td> </td>
                  <td align="center">5.48 (1.59-18.9)</td>
                  <td align="center">&lt;0.01</td>
                  <td> </td>
                  <td> </td>
                  <td align="center">1.21 (0.41-3.53)</td>
                  <td align="center">0.72</td>
                </tr>
                <tr>
                  <td>Diabetes</td>
                  <td> </td>
                  <td> </td>
                  <td align="center">1.49 (0.71-3.11)</td>
                  <td align="center">0.29</td>
                  <td> </td>
                  <td> </td>
                  <td align="center">0.34 (0.11-1.02)</td>
                  <td align="center">0.06</td>
                  <td> </td>
                  <td> </td>
                  <td align="center">0.16 (0.02-1.23)</td>
                  <td align="center">0.08</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN2001">
                <p>*Adjusted for age, sex, smoking, hypertension and diabetes.</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
        </p>
        <p>In multivariable logistic regression, moderate/severe MR was independently associated with older age, Black race, and obesity. Moderate/severe AR was associated with older age and hypertension. Moderate/severe TR was associated with female sex and Black race (<xref ref-type="table" rid="t2001">Table 2</xref>).</p>
        <p>As expected, the moderate/severe VHD group showed larger left atrial and ventricular dimensions, higher LV mass, lower relative wall thickness and LV ejection fraction, and a higher prevalence of pulmonary hypertension compared with the other groups (<xref ref-type="table" rid="t1001">Table 1</xref>).</p>
        <p>Small differences in remodeling patterns were identified across the most prevalent moderate/severe VHD phenotypes (MR, AR, and TR), even after adjustment for age and sex (<xref ref-type="sec" rid="suppl001">Supplemental Material &#8211; Figure 3</xref>).</p>
        <p>A total of 355 participants (10.9%) died during a mean follow-up of 4,260 &#177; 840 days. Participants with moderate/severe VHD had worse survival, as shown in the Kaplan&#8211;Meier curve (log-rank p &lt; 0.001; <xref ref-type="fig" rid="f03001">Figure 2</xref> and <xref ref-type="fig" rid="f01001">Central Illustration</xref>). Moderate/severe VHD was an independent predictor of mortality (adjusted HR: 3.7; 95% CI: 2.17&#8211;6.31), after adjustment for age, sex, and hypertension.</p>
        <p>
          <fig id="f03001">
            <label>Figure 2</label>
            <caption>
              <title>&#8211; Kaplan-Meier survival curves of included ELSA participants, according to valvular heart disease severity.</title>
            </caption>
            <graphic xlink:href="1678-4170-abc-123-06-e20260060-60060-gf03-en.tif"/></fig>
        </p>
      </sec>
      <sec sec-type="discussion">
        <title>Discussion</title>
        <p>In a middle-aged Latin American population, we found that VHD is more prevalent among older individuals. Participants with moderate/severe VHD had a higher burden of cardiovascular risk factors, more pronounced cardiac remodeling, lower LV ejection fraction, and poorer survival compared with those without significant valve disease.</p>
        <p>In our population, the prevalence of moderate/severe VHD was similar to that reported in a Hispanic/Latino cohort from the United States and in a recent community-based study of asymptomatic elderly individuals.<sup><xref ref-type="bibr" rid="B1">1</xref>,<xref ref-type="bibr" rid="B3">3</xref></sup> Consistent with previous studies, we found that age was independently associated with all types of moderate/severe valvular regurgitation.<sup><xref ref-type="bibr" rid="B1">1</xref>,<xref ref-type="bibr" rid="B5">5</xref>,<xref ref-type="bibr" rid="B13">13</xref></sup> However, studies with a higher proportion of elderly participants have reported a greater prevalence of moderate/severe VHD than observed in our cohort.<sup><xref ref-type="bibr" rid="B5">5</xref>,<xref ref-type="bibr" rid="B7">7</xref>,<xref ref-type="bibr" rid="B14">14</xref></sup> The progressive hemodynamic stress imposed on cardiac valves over time likely contributes to degenerative changes, supporting the increase in VHD prevalence with advancing age. Among the various lesions, MR was the most frequent, consistent with most previously published population-based studies.<sup><xref ref-type="bibr" rid="B1">1</xref>-<xref ref-type="bibr" rid="B3">3</xref>,<xref ref-type="bibr" rid="B7">7</xref></sup> Aortic stenosis is also a highly prevalent valvular disease, but its frequency increases substantially with population aging.<sup><xref ref-type="bibr" rid="B5">5</xref>,<xref ref-type="bibr" rid="B15">15</xref>-<xref ref-type="bibr" rid="B19">19</xref></sup> In our sample, we observed a higher overall prevalence of aortic regurgitation than aortic stenosis, likely reflecting the relatively younger mean age of our cohort (60 years).</p>
        <p>The ELSA-Brasil cohort, which includes participants from six states across three major regions of the country, captures Brazil&#8217;s socioeconomic, racial, and climatic diversity. Notably, 44% of our sample consisted of non-White participants, and individuals who self-identified as Black had higher rates of moderate/severe MR and TR. We were unable to determine whether genetic factors, social determinants, or differences in access to health care contributed to these findings. Nonetheless, by including a population group that has been underrepresented in prior research, our study underscores the need for broader and more inclusive investigations.</p>
        <p>As in other studies, we found that the moderate/severe VHD group had a higher prevalence of cardiovascular diseases.<sup><xref ref-type="bibr" rid="B2">2</xref>,<xref ref-type="bibr" rid="B3">3</xref>,<xref ref-type="bibr" rid="B7">7</xref></sup> Notably, hypertension was independently associated with AR, consistent with reports suggesting that hypertension may predispose individuals to aortic root enlargement and, consequently, to aortic regurgitation.<sup><xref ref-type="bibr" rid="B20">20</xref></sup></p>
        <p>We observed larger cardiac chambers in the moderate/severe VHD group, consistent with the ventricular and atrial remodeling that occurs in response to the hemodynamic burden imposed by VHD. Most previous studies have also reported larger left atrial and ventricular dimensions, higher LV mass, lower LV ejection fraction, and pulmonary hypertension in participants with VHD.<sup><xref ref-type="bibr" rid="B1">1</xref>,<xref ref-type="bibr" rid="B5">5</xref>,<xref ref-type="bibr" rid="B7">7</xref></sup> This phenotype was particularly evident in moderate/severe MR, which may reflect the consequences of chronic volume overload and increased wall stress on cardiac structure and function.</p>
        <p>Socioeconomic factors may also influence the burden of VHD, as delays and barriers in accessing diagnosis, treatment, and preventive care can critically affect disease outcomes. In middle-income countries such as Brazil, where social conditions may be more precarious, the prevalence of VHD and the likelihood of unfavorable outcomes may be higher.</p>
        <p>Structural and functional cardiac changes associated with VHD may contribute to worse clinical outcomes and could explain the lower survival observed in participants with moderate/severe VHD in our study, as well as in previous research.<sup><xref ref-type="bibr" rid="B5">5</xref>,<xref ref-type="bibr" rid="B21">21</xref></sup> Given global population aging and the strong association between moderate/severe VHD and advancing age, understanding the progression and mortality associated with VHD is increasingly important.</p>
        <p>We were not able to identify a specific echocardiographic pattern typical of rheumatic heart disease within this middle-aged population. In younger individuals, the presence of combined valve regurgitation or mixed valve disease is an important marker of rheumatic involvement and is commonly used in large-scale screening. However, in older populations, the specificity of these findings is limited, as degenerative and functional etiologies become more prevalent and overshadow rheumatic patterns.<sup><xref ref-type="bibr" rid="B22">22</xref></sup></p>
        <p>Our study has several limitations. The cohort consisted of civil servants from universities and research institutions, which may not fully represent the general Brazilian population. As an occupational cohort, it is possible that individuals with more disabling illnesses were not included. The relatively narrow age range, with most participants being middle-aged, may have led to an underestimation of moderate to severe cases, and we were unable to determine the etiology of major native VHD. Additionally, the cross-sectional design prevents assessment of how VHD influences long-term outcomes, including its direct contribution to mortality. Furthermore, the study followed a predefined protocol, and echocardiographic assessments were qualitative, without detailed quantification of specific valvular lesions.</p>
        <p>In this Brazilian middle-aged cohort, VHD was found to be prevalent and increased with age. Participants with moderate/severe VHD had a higher burden of comorbidities, more pronounced cardiac remodeling, worse systolic function, and poorer survival. Understanding VHD within the current Brazilian context may contribute to improved public health planning and earlier identification and management of the disease.</p>
      </sec>
      <sec id="suppl001" sec-type="supplementary-material">
        <title>Supplemental Materials</title>
        <supplementary-material id="suppl01en">
          <label>Supplementary material</label>
          <media mime-subtype="pdf" mimetype="application" xlink:href="https://minio.scielo.br/documentstore/1678-4170/x3gGf3xfXWcCqWZQQ7CxYHz/8739ebc0e09fdbd59f25339fa691d33af5f01879.pdf"/>
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    <back>
      <ack>
        <title>Acknowledgments</title>
        <p>The authors would like to acknowledge all ELSA-Brasil participants for their valuable contribution to this study.</p>
      </ack>
      <fn-group>
        <fn fn-type="other">
          <label>Study Association:</label>
          <p> This article is part of the thesis of Doctoral submitted by Giulia Bevilacqua Schmitz, from Post-Graduate Program in Cardiology and Cardiovascular Sciences, Medical School, Universidade Federal do Rio Grande do Sul.</p>
        </fn>
        <fn fn-type="other">
          <label>Ethics Approval and Consent to Participate:</label>
          <p> This study was approved by the Ethics Committee of the Hospital de Cl&#237;nicas de Porto Alegre under the protocol number 0017.1.069.000-6,194/06. All the procedures in this study were in accordance with the 1975 Helsinki Declaration, updated in 2013. Informed consent was obtained from all participants included in the study.</p>
        </fn>
        <fn fn-type="other">
          <label>Use of Artificial Intelligence:</label>
          <p> The authors did not use any artificial intelligence tools in the development of this work.</p>
        </fn>
        <fn fn-type="data-availability" specific-use="data-available-upon-request">
          <label>Availability of Research Data:</label>
          <p> All datasets supporting the results of this study are available upon request from the corresponding author</p>
        </fn>
        <fn fn-type="supplementary-material" id="supplfn001">
          <label>*Supplemental Materials</label>
          <p> For additional information, please <ext-link ext-link-type="uri" xlink:href="https://abccardiol.org/supplementary-material/2026/12306/2026_0060_supplementary_material.pdf">click here</ext-link>.</p>
        </fn>
        <fn fn-type="financial-disclosure">
          <label>Sources of Funding:</label>
          <p> This study was funded by Brazilian Ministry of Health (Science and Technology Department) and the Brazilian Ministry of Science, Technology, and Innovation (Financiadora de Estudos e Projetos &#8211; grants 01 06 0010.00, 01 10 0643.00 RS, 01 06 0212.00 BA, 01 06 0300.00 ES, 01 06 0278.00 MG, 01 06 0115.00 SP, 01 06 0071.00 RJ), as well as by CNPq (the Brazilian National Council for Scientific and Technological Development).</p>
        </fn>
      </fn-group>
    </back>
  </sub-article>
</article>
