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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">VBdrFFYqYbrqWKfJ65rKdPw</article-id>
      <article-id specific-use="scielo-v2" pub-id-type="publisher-id">S0066-782X2025001100309</article-id>
      <article-id pub-id-type="other">00309</article-id>
      <article-id pub-id-type="doi">10.36660/abc.20250189</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Artigo Original</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Proje&#231;&#245;es de Mortalidade por Doen&#231;a Isqu&#234;mica do Cora&#231;&#227;o, Acidente Vascular Cerebral e Doen&#231;a Arterial Perif&#233;rica no Brasil at&#233; 2040: Uma Abordagem de Modelagem Bayesiana</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-5116-5062</contrib-id>
          <name>
            <surname>Salerno</surname>
            <given-names>Pedro Rafael Vieira de Oliveira</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</role>
          <role>An&#225;lise estat&#237;stica</role>
          <role>Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do</role>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Cotton</surname>
            <given-names>Antoinette</given-names>
          </name>
          <role>Concep&#231;&#227;o e desenho da pesquisa</role>
          <role>An&#225;lise estat&#237;stica</role>
          <role>Reda&#231;&#227;o do manuscrito</role>
          <role>Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do</role>
          <xref ref-type="aff" rid="aff3">
            <sup>3</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Nascimento</surname>
            <given-names>Bruno R.</given-names>
          </name>
          <role>Concep&#231;&#227;o e desenho da pesquisa</role>
          <role>Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do</role>
          <xref ref-type="aff" rid="aff4">
            <sup>4</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Chen</surname>
            <given-names>Zhuo</given-names>
          </name>
          <role>Obten&#231;&#227;o de dados</role>
          <role>An&#225;lise estat&#237;stica</role>
          <role>Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do</role>
          <xref ref-type="aff" rid="aff2">
            <sup>2</sup>
          </xref>
          <xref ref-type="aff" rid="aff3">
            <sup>3</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Pereira</surname>
            <given-names>Gabriel Tensol Rodrigues</given-names>
          </name>
          <role>Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do</role>
          <xref ref-type="aff" rid="aff3">
            <sup>3</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Abizaid</surname>
            <given-names>Alexandre A.</given-names>
          </name>
          <role>Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do</role>
          <xref ref-type="aff" rid="aff5">
            <sup>5</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-8122-6647</contrib-id>
          <name>
            <surname>Dallan</surname>
            <given-names>Luis Augusto Palma</given-names>
          </name>
          <role>Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do</role>
          <xref ref-type="aff" rid="aff2">
            <sup>2</sup>
          </xref>
          <xref ref-type="aff" rid="aff6">
            <sup>6</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0009-0007-4241-0656</contrib-id>
          <name>
            <surname>Salerno</surname>
            <given-names>Pedro Rafael</given-names>
          </name>
          <role>Reda&#231;&#227;o do manuscrito</role>
          <xref ref-type="aff" rid="aff7">
            <sup>7</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Al-Kindi</surname>
            <given-names>Sadeer</given-names>
          </name>
          <role>Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do</role>
          <xref ref-type="aff" rid="aff8">
            <sup>8</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Petermann-Rocha</surname>
            <given-names>Fanny</given-names>
          </name>
          <role>Concep&#231;&#227;o e desenho da pesquisa</role>
          <role>Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do</role>
          <xref ref-type="aff" rid="aff9">
            <sup>9</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Deo</surname>
            <given-names>Salil V.</given-names>
          </name>
          <role>Concep&#231;&#227;o e desenho da pesquisa</role>
          <role>An&#225;lise e interpreta&#231;&#227;o dos dados</role>
          <role>An&#225;lise estat&#237;stica</role>
          <role>Reda&#231;&#227;o do manuscrito</role>
          <role>Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do</role>
          <xref ref-type="aff" rid="aff3">
            <sup>3</sup>
          </xref>
          <xref ref-type="aff" rid="aff10">
            <sup>10</sup>
          </xref>
          <xref ref-type="aff" rid="aff11">
            <sup>11</sup>
          </xref>
        </contrib>
      </contrib-group>
      <aff id="aff1">
        <label>1</label>
        <institution content-type="orgname">Icahn School of Medicine at Mt. Sinai</institution>
        <addr-line>
          <named-content content-type="city">Queens</named-content>
          <named-content content-type="state">NY</named-content>
        </addr-line>
        <country country="US">EUA</country>
        <institution content-type="original">Department of Medicine, NYC Health + Hospitals/Elmhurst, Icahn School of Medicine at Mt. Sinai, Queens, NY &#8211; EUA</institution>
      </aff>
      <aff id="aff2">
        <label>2</label>
        <institution content-type="orgname">University Hospitals of Cleveland</institution>
        <addr-line>
          <named-content content-type="city">Cleveland</named-content>
          <named-content content-type="state">Ohio</named-content>
        </addr-line>
        <country country="US">EUA</country>
        <institution content-type="original">University Hospitals of Cleveland, Cleveland, Ohio &#8211; EUA</institution>
      </aff>
      <aff id="aff3">
        <label>3</label>
        <institution content-type="orgname">Case Western Reserve University</institution>
        <addr-line>
          <named-content content-type="city">Cleveland </named-content>
        </addr-line>
        <country country="US">EUA</country>
        <institution content-type="original">Case Western Reserve University, Cleveland &#8211; EUA</institution>
      </aff>
      <aff id="aff4">
        <label>4</label>
        <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">Universidade Federal de Minas Gerais, Belo Horizonte, MG &#8211; Brasil</institution>
      </aff>
      <aff id="aff5">
        <label>5</label>
        <institution content-type="orgname">Hospital Israelita Albert Einstein</institution>
        <addr-line>
          <named-content content-type="city">S&#227;o Paulo</named-content>
          <named-content content-type="state">SP</named-content>
        </addr-line>
        <country country="BR">Brasil</country>
        <institution content-type="original">Hospital Israelita Albert Einstein, S&#227;o Paulo, SP &#8211; Brasil</institution>
      </aff>
      <aff id="aff6">
        <label>6</label>
        <institution content-type="orgdiv2">Instituto do Cora&#231;&#227;o do Hospital das Cl&#237;nicas</institution>
        <institution content-type="orgdiv1">Faculdade de Medicina</institution>
        <institution content-type="orgname">Universidade de S&#227;o Paulo</institution>
        <addr-line>
          <named-content content-type="city">S&#227;o Paulo</named-content>
          <named-content content-type="state">SP</named-content>
        </addr-line>
        <country country="BR">Brasil</country>
        <institution content-type="original">Instituto do Cora&#231;&#227;o do Hospital das Cl&#237;nicas da Faculdade de Medicina da Universidade de S&#227;o Paulo, S&#227;o Paulo, SP &#8211; Brasil</institution>
      </aff>
      <aff id="aff7">
        <label>7</label>
        <institution content-type="orgname">Universidade Cat&#243;lica de Pernambuco</institution>
        <addr-line>
          <named-content content-type="city">Recife</named-content>
          <named-content content-type="state">PE</named-content>
        </addr-line>
        <country country="BR">Brasil</country>
        <institution content-type="original">Universidade Cat&#243;lica de Pernambuco, Recife, PE &#8211; Brasil</institution>
      </aff>
      <aff id="aff8">
        <label>8</label>
        <institution content-type="orgname">Center for Health and Nature Houston Methodist</institution>
        <addr-line>
          <named-content content-type="city">Houston</named-content>
        </addr-line>
        <country country="US">EUA</country>
        <institution content-type="original">Center for Health and Nature Houston Methodist, Houston &#8211; EUA</institution>
      </aff>
      <aff id="aff9">
        <label>9</label>
        <institution content-type="orgname">Universidad Diego Portales</institution>
        <addr-line>
          <named-content content-type="city">Santiago</named-content>
        </addr-line>
        <country country="CL">Chile</country>
        <institution content-type="original">Universidad Diego Portales, Santiago &#8211; Chile</institution>
      </aff>
      <aff id="aff10">
        <label>10</label>
        <institution content-type="orgname">Louis Stokes VA Medical Center</institution>
        <addr-line>
          <named-content content-type="city">Cleveland</named-content>
          <named-content content-type="state">Ohio</named-content>
        </addr-line>
        <country country="US">EUA</country>
        <institution content-type="original">Louis Stokes VA Medical Center, Cleveland, Ohio &#8211; EUA</institution>
      </aff>
      <aff id="aff11">
        <label>11</label>
        <institution content-type="orgname">University of Glasgow</institution>
        <addr-line>
          <named-content content-type="city">Glasgow</named-content>
        </addr-line>
        <country country="GB">Inglaterra</country>
        <institution content-type="original">University of Glasgow, Glasgow &#8211; Inglaterra</institution>
      </aff>
      <author-notes>
        <corresp id="c01"><label>Correspond&#234;ncia:</label> Salil V. Deo Case Western Reserve University School of Medicine Health Education Campus - 9501 Euclid Ave, Cleveland, OH 44106. Email: <email>svd14@case.edu</email> </corresp>
        <fn fn-type="edited-by">
          <label>Editor respons&#225;vel pela revis&#227;o:</label>
          <p>Marcio Bittencourt</p>
        </fn>
        <fn fn-type="coi-statement">
          <label>Potencial conflito de interesse:</label>
          <p>N&#227;o h&#225; conflito com o presente artigo.</p>
        </fn>
      </author-notes>
      <pub-date date-type="pub" publication-format="electronic">
        <day>16</day>
        <month>01</month>
        <year>2026</year>
      </pub-date>
      <pub-date date-type="collection" publication-format="electronic">
        <month>11</month>
        <year>2025</year>
      </pub-date>
      <volume>122</volume>
      <issue>11</issue>
      <elocation-id>e20250189</elocation-id>
      <history>
        <date date-type="received">
          <day>16</day>
          <month>03</month>
          <year>2025</year>
        </date>
        <date date-type="rev-recd">
          <day>13</day>
          <month>07</month>
          <year>2025</year>
        </date>
        <date date-type="accepted">
          <day>20</day>
          <month>08</month>
          <year>2025</year>
        </date>
      </history>
      <permissions>
        <license license-type="open-access" xlink:href="https://creativecommons.org/licenses/by/4.0/" xml:lang="en">
          <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> As doen&#231;as cardiovasculares ateroscler&#243;ticas &#8212; especialmente a doen&#231;a isqu&#234;mica do cora&#231;&#227;o (DIC), o acidente vascular cerebral (AVC) e a doen&#231;a arterial perif&#233;rica (DAP) &#8212; s&#227;o a principal causa de mortalidade cardiovascular no Brasil.</p>
        </sec>
        <sec>
          <title>Objetivos</title>
          <p> Projetar as tend&#234;ncias de mortalidade por DIC, AVC e DAP no Brasil at&#233; 2040.</p>
        </sec>
        <sec>
          <title>M&#233;todos</title>
          <p> As contagens anuais de &#243;bitos (1990-2021) por DIC, AVC e DAP entre indiv&#237;duos de 40 a 79 anos foram obtidas a partir do estudo Carga Global de Doen&#231;as (<italic>Global Burden of Disease</italic>, GBD) de 2021. Utilizaram-se estimativas populacionais de meio de ano tanto para o per&#237;odo observado (1990-2021) quanto para o projetado (2022-2040). Foram calculadas as taxas de mortalidade brutas e padronizadas por idade. Modelos bayesianos idade-per&#237;odo-coorte foram aplicados para projetar as taxas de mortalidade de 2022 a 2040. Foram computadas as varia&#231;&#245;es percentuais relativas e as estimativas anuais de varia&#231;&#227;o percentual (EAVPs). As proje&#231;&#245;es (por 100.000 habitantes) s&#227;o apresentadas como medianas com intervalos de incerteza (IIs) de 95%, e as EAVPs incluem intervalos de confian&#231;a (ICs) de 95% derivados por <italic>bootstrap</italic>.</p>
        </sec>
        <sec>
          <title>Resultados</title>
          <p> Entre 1990 e 2040, estima-se que a popula&#231;&#227;o brasileira de 40 a 79 anos aumente em 237,82%. A taxa de mortalidade padronizada por idade para DIC dever&#225; apresentar uma redu&#231;&#227;o de 14,16% [de 118,61 em 2021 para 101,82 em 2040 (II 95%, 0,36-203,27)] (EAVP: -0,83% [IC 95%, -0,84 a -0,83]); e, para AVC, uma redu&#231;&#227;o de 17,36% [de 84,58 para 69,90 (II 95%, 0-152,48)] (EAVP: -1,07% [IC 95%, -1,10 a -1,04]). Em contraste, projeta-se que a mortalidade por DAP aumente em 10,99% [de 1,82 para 2,02 (II 95%, 0-5,03)] (EAVP: 0,45% [IC 95%, 0,30-0,59]). Adicionalmente, as taxas de mortalidade padronizadas por idade, espec&#237;ficas por sexo, mostraram varia&#231;&#245;es consider&#225;veis. Para a DIC, projeta-se uma redu&#231;&#227;o de 25,31% entre homens (EAVP, -1,56% [IC 95%, -1,57 a -1,55]), enquanto entre mulheres dever&#225; haver um aumento de 4,12% (EAVP: 0,14% [IC 95%, 0,13-0,16]). A mortalidade por AVC dever&#225; reduzir em 30,00% entre homens (EAVP, -1,94% [IC 95%: -1,96 a -1,91]) e em 4,52% entre mulheres (EAVP: -0,33% [IC 95%, -0,37 a -0,29]). Em contrapartida, a mortalidade por DAP dever&#225; crescer 14,64% entre homens (EAVP, 0,55% [IC 95%: 0,38-0,71]) e 21,92% entre mulheres (EAVP: 0,91% [IC 95%: 0,78-1,02]).</p>
        </sec>
        <sec>
          <title>Conclus&#227;o</title>
          <p> Embora se preveja redu&#231;&#227;o nas taxas de mortalidade por DIC e AVC, espera-se um aumento na mortalidade por DAP &#8212; especialmente entre as mulheres &#8212;, o que evidencia a necessidade urgente de interven&#231;&#245;es em sa&#250;de p&#250;blica espec&#237;ficas por sexo e por tipo de doen&#231;a.</p>
        </sec>
      </abstract>
      <abstract abstract-type="graphical">
        <p>
          <fig id="f01">
            <label>Figura Central:</label>
            <caption>
              <title>Proje&#231;&#245;es de Mortalidade por Doen&#231;a Isqu&#234;mica do Cora&#231;&#227;o, Acidente Vascular Cerebral e Doen&#231;a Arterial Perif&#233;rica no Brasil at&#233; 2040: Uma Abordagem de Modelagem Bayesiana</title>
            </caption>
            <attrib>Taxas de mortalidade padronizadas por idade projetadas (por 100.000 habitantes) para AVC, DIC e DAP no Brasil. As proje&#231;&#245;es foram derivadas por meio de modelagem bayesiana, com base em dados observados de mortalidade de 1990 a 2021 e em estimativas populacionais de meio de ano para o per&#237;odo de 2022 a 2040. Os valores para 2021 e 2040 s&#227;o apresentados, juntamente com seus respectivos II 95%. Os resultados indicam redu&#231;&#245;es projetadas nas taxas de mortalidade por AVC e DIC de 17,36% e 14,16%, respectivamente, enquanto se espera um aumento de 10,99% na mortalidade por DAP. As taxas espec&#237;ficas de mortalidade para 2021 e 2040 est&#227;o apresentadas abaixo de cada condi&#231;&#227;o. AVC: acidente vascular cerebral; BAPC: modelo bayesiano idade-per&#237;odo-coorte; GBD: Global Burden of Disease; DAP: doen&#231;a arterial perif&#233;rica; DIC: doen&#231;a isqu&#234;mica do cora&#231;&#227;o; II: intervalo de incerteza.</attrib>
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        </p>
      </abstract>
      <kwd-group xml:lang="pt">
        <title>Palavras-chave</title>
        <kwd>Isquemia Mioc&#225;rdica</kwd>
        <kwd>Acidente Vascular Cerebral</kwd>
        <kwd>Doen&#231;a Arterial Perif&#233;rica</kwd>
        <kwd>Mortalidade</kwd>
        <kwd>Brasil</kwd>
      </kwd-group>
      <funding-group>
        <funding-statement><bold>Fontes de financiamento:</bold>O presente estudo n&#227;o teve fontes de financiamento externas.</funding-statement>
      </funding-group>
      <counts>
        <fig-count count="10"/>
        <table-count count="2"/>
        <equation-count count="0"/>
        <ref-count count="41"/>
      </counts>
    </article-meta>
  </front>
  <body>
    <sec sec-type="intro">
      <title>Introdu&#231;&#227;o</title>
      <p>As doen&#231;as cardiovasculares (DCVs) ateroscler&#243;ticas englobam 3 condi&#231;&#245;es principais: doen&#231;a isqu&#234;mica do cora&#231;&#227;o (DIC), acidente vascular cerebral (AVC) e doen&#231;a arterial perif&#233;rica (DAP). Em 2013, DIC e AVC juntos foram respons&#225;veis por 247,9 &#243;bitos por 100.000 habitantes em todo o mundo.<sup><xref ref-type="bibr" rid="B1">1</xref></sup> Por muitos anos, ambas t&#234;m figurado consistentemente entre as principais causas de mortalidade cardiovascular na maioria dos pa&#237;ses. Em 2019, o estudo Carga Global de Doen&#231;a (<italic>Global Burden of Disease</italic>, GBD) relatou que 113 milh&#245;es de adultos em todo o mundo eram afetados pela DAP, com 42% dos &#243;bitos relacionados ocorrendo em pa&#237;ses de baixa e m&#233;dia renda, incluindo o Brasil.<sup><xref ref-type="bibr" rid="B2">2</xref></sup> Segundo o relat&#243;rio Estat&#237;stica Cardiovascular &#8211; Brasil 2023, as DCVs continuam sendo a principal causa de morte no pa&#237;s.<sup><xref ref-type="bibr" rid="B3">3</xref></sup></p>
      <p>Embora a taxa de mortalidade padronizada por idade por DCV tenha diminu&#237;do nas &#250;ltimas d&#233;cadas no Brasil, a preval&#234;ncia dessas condi&#231;&#245;es aumentou em 26%.<sup><xref ref-type="bibr" rid="B4">4</xref>,<xref ref-type="bibr" rid="B5">5</xref></sup> As taxas de obesidade e dislipidemia permanecem elevadas e, de acordo com o relat&#243;rio de 2024 da Organiza&#231;&#227;o Mundial da Sa&#250;de (OMS), o Brasil figura entre os pa&#237;ses com maior uso de tabaco. Al&#233;m disso, estima-se que a mortalidade atribu&#237;vel ao diabetes no pa&#237;s aumente em 144% nas pr&#243;ximas 2 d&#233;cadas.<sup><xref ref-type="bibr" rid="B4">4</xref>,<xref ref-type="bibr" rid="B6">6</xref></sup></p>
      <p>Reconhecendo o impacto negativo das condi&#231;&#245;es cardiovasculares na sa&#250;de da popula&#231;&#227;o, o Congresso Nacional Brasileiro promulgou, em 1990, a Lei n&#186; 8.080, que instituiu o Sistema &#218;nico de Sa&#250;de (SUS), sistema p&#250;blico de sa&#250;de gratuito e universal. Atualmente, o SUS atende mais de 70% da popula&#231;&#227;o brasileira.<sup><xref ref-type="bibr" rid="B7">7</xref></sup> Adicionalmente, o Minist&#233;rio da Sa&#250;de implementou o Programa Sa&#250;de da Fam&#237;lia em meados da d&#233;cada de 1990, seguido por estrat&#233;gias de preven&#231;&#227;o prim&#225;ria em 2002 e pela ado&#231;&#227;o de uma pol&#237;tica de cobertura de medicamentos gen&#233;ricos para o tratamento da hipertens&#227;o, diabetes e dislipidemia.<sup><xref ref-type="bibr" rid="B8">8</xref></sup> Essas iniciativas contribu&#237;ram para melhorias na sa&#250;de da popula&#231;&#227;o. No entanto, &#224; medida que as pol&#237;ticas p&#250;blicas evoluem e as op&#231;&#245;es terap&#234;uticas se expandem, a carga atribu&#237;vel &#224;s DCVs e seus componentes pode se modificar. Assim, compreender a trajet&#243;ria futura dessas condi&#231;&#245;es &#233; essencial para orientar estrat&#233;gias nacionais de sa&#250;de.</p>
      <p>Alguns pa&#237;ses, como Estados Unidos, Jap&#227;o e Reino Unido, j&#225; realizaram proje&#231;&#245;es sobre a sa&#250;de cardiovascular.<sup><xref ref-type="bibr" rid="B9">9</xref>,<xref ref-type="bibr" rid="B10">10</xref></sup> Nos EUA e no Jap&#227;o, projeta-se redu&#231;&#227;o na mortalidade por DIC, enquanto a mortalidade por AVC dever&#225; permanecer relativamente est&#225;vel. No entanto, tais achados n&#227;o podem ser generalizados para outros contextos, devido &#224;s varia&#231;&#245;es na estrutura populacional, nas taxas de fecundidade, nos padr&#245;es de envelhecimento e nos fluxos migrat&#243;rios. Como o Brasil est&#225; entre os pa&#237;ses mais populosos do mundo, sua contribui&#231;&#227;o para as estimativas globais &#233; significativa.</p>
      <p>Assim, o presente estudo teve como objetivo projetar as taxas de mortalidade por DIC, AVC e DAP entre adultos brasileiros com idade entre 40 e 79 anos at&#233; 2040, com base em dados observados de 1990 a 2021.</p>
    </sec>
    <sec sec-type="methods">
      <title>M&#233;todos</title>
      <sec>
        <title>Fonte de dados</title>
        <sec>
          <title>Mortalidade por DIC, AVC e DAP</title>
          <p>A principal fonte de dados deste estudo foi o estudo GBD 2021.<sup><xref ref-type="bibr" rid="B11">11</xref></sup> O GBD, um cons&#243;rcio global com mais de 12.000 colaboradores, fornece dados padronizados sobre incapacidade e mortalidade atribu&#237;veis a diversas condi&#231;&#245;es de sa&#250;de e fatores de risco em 204 pa&#237;ses e territ&#243;rios.<sup><xref ref-type="bibr" rid="B12">12</xref></sup> A atualiza&#231;&#227;o de 2021 oferece acesso p&#250;blico por meio da ferramenta de consulta da <italic>Global Health Data Exchange</italic> (GHDx) (http://ghdx.healthdata.org/gbd-results-tool).<sup><xref ref-type="bibr" rid="B11">11</xref></sup> Como signat&#225;rio das <italic>Guidelines for Accurate and Transparent Health Estimates Reporting</italic> da OMS, o GBD aplica um processamento padronizado de dados para garantir a comparabilidade entre os pa&#237;ses.<sup><xref ref-type="bibr" rid="B12">12</xref></sup></p>
          <p>Utilizando o GHDx, extra&#237;mos as contagens anuais de &#243;bitos atribu&#237;dos &#224; DIC, AVC e DAP no Brasil em intervalos et&#225;rios de 5 anos (40-44, 45-49, 50-54, 55-59, 60-64, 65-69, 70-74 e 75-79 anos), de 1990 a 2021. O GBD 2021 define DIC como um composto de infarto agudo do mioc&#225;rdio, angina est&#225;vel cr&#244;nica, doen&#231;a arterial coronariana e miocardiopatia isqu&#234;mica, e define DAP como &#237;ndice tornozelo-braquial &lt; 0,9.<sup><xref ref-type="bibr" rid="B13">13</xref></sup> De acordo com o GBD, a fonte original dos dados de mortalidade foi o Sistema de Informa&#231;&#245;es sobre Mortalidade (SIM), um banco de dados nacional de atestados de &#243;bito curado e avaliado quanto &#224; qualidade, gerenciado pelo Minist&#233;rio da Sa&#250;de do Brasil.<sup><xref ref-type="bibr" rid="B14">14</xref></sup> Os dados brutos foram processados utilizando o modelo <italic>Cause of Death Ensemble</italic> (CODEm), uma estrutura de regress&#227;o geoespacial bayesiana desenvolvida pelo <italic>Institute for Health Metrics and Evaluation</italic> (Seattle, WA).<sup><xref ref-type="bibr" rid="B13">13</xref></sup> Informa&#231;&#245;es adicionais sobre os dados do GBD 2021 utilizados neste estudo est&#227;o dispon&#237;veis no <xref ref-type="supplementary-material" rid="suppl01">material suplementar</xref>.</p>
        </sec>
        <sec>
          <title>Estimativas populacionais</title>
          <p>Tamb&#233;m obtivemos estimativas populacionais de meio de ano para os mesmos intervalos et&#225;rios (40-44 a 75-79 anos) no per&#237;odo de 1990 a 2040, a partir do GBD 2021.<sup><xref ref-type="bibr" rid="B15">15</xref>,<xref ref-type="bibr" rid="B16">16</xref></sup> Tais estimativas s&#227;o oriundas do Instituto Brasileiro de Geografia e Estat&#237;stica, respons&#225;vel pelos censos nacionais no Brasil.<sup><xref ref-type="bibr" rid="B15">15</xref></sup> Os dados foram extra&#237;dos para a popula&#231;&#227;o geral, bem como desagregados por sexo.</p>
        </sec>
      </sec>
    </sec>
    <sec>
      <title>An&#225;lise estat&#237;stica</title>
      <p>Inicialmente, calculamos as taxas de mortalidade anuais observadas, brutas e padronizadas por idade (por 100.000 habitantes), para DIC, AVC e DAP entre 1990 e 2021. As taxas padronizadas por idade e os respectivos intervalos de confian&#231;a (ICs) 95% foram calculados utilizando a popula&#231;&#227;o de meio de ano de 1990 como padr&#227;o, com os ICs estimados por meio do m&#233;todo delta.</p>
      <p>Em seguida, aplicamos modelos bayesianos idade-per&#237;odo-coorte (IPC) aos dados observados (1990-2021) para projetar as taxas de mortalidade por DIC, AVC e DAP at&#233; 2040. Os modelos IPC permitem a modelagem simult&#226;nea dos efeitos de idade, per&#237;odo e coorte em uma &#250;nica equa&#231;&#227;o de regress&#227;o e podem acomodar rela&#231;&#245;es n&#227;o lineares.<sup><xref ref-type="bibr" rid="B17">17</xref></sup> Utilizamos <italic>priors</italic> do tipo <italic>random walk 2</italic> com distribui&#231;&#227;o log-gama, e modelamos a vari&#225;vel desfecho (eventos de mortalidade) por meio de uma estrutura de regress&#227;o linear generalizada com fun&#231;&#227;o <italic>log-link</italic> e distribui&#231;&#227;o de Poisson.</p>
      <p>Embora existam diversas formula&#231;&#245;es poss&#237;veis para os modelos IPC, estudos recentes de simula&#231;&#227;o demonstraram que os modelos bayesianos IPC oferecem melhor acur&#225;cia preditiva.<sup><xref ref-type="bibr" rid="B18">18</xref></sup> As estimativas dos modelos ajustados foram obtidas utilizando a <italic>integrated nested Laplace approximation</italic>, uma abordagem computacionalmente eficiente, conhecida por produzir estimativas posteriores est&#225;veis e confi&#225;veis sem problemas de converg&#234;ncia, compar&#225;veis &#224;s obtidas por simula&#231;&#245;es de Cadeia de Markov de Monte Carlo.<sup><xref ref-type="bibr" rid="B19">19</xref></sup> Informa&#231;&#245;es detalhadas sobre a especifica&#231;&#227;o dos priors, metodologia de proje&#231;&#227;o e procedimentos de avalia&#231;&#227;o dos modelos est&#227;o dispon&#237;veis no material suplementar.</p>
      <p>Os modelos foram ajustados para a popula&#231;&#227;o brasileira total e separadamente para homens e mulheres. Para cada grupo, as taxas de mortalidade foram projetadas para todos os intervalos et&#225;rios de 5 anos definidos, e as taxas padronizadas por idade foram novamente indexadas &#224; popula&#231;&#227;o de meio de ano de 1990. As taxas projetadas s&#227;o apresentadas como medianas com intervalos de incerteza (IIs) de 95%. Tamb&#233;m calculamos a varia&#231;&#227;o percentual relativa e a estimativa anual de varia&#231;&#227;o percentual (EAVP) entre o &#250;ltimo ano observado (2021) e o &#250;ltimo ano projetado (2040). As EAVPs foram estimadas por regress&#227;o linear generalizada com fun&#231;&#227;o log-link, e os ICs 95% foram obtidos por reamostragem <italic>bootstrap</italic>.</p>
      <p>Todas as an&#225;lises foram realizadas no R vers&#227;o 4.3.0 (<italic>R Foundation for Statistical Computing</italic>, Viena, &#193;ustria). Como o estudo utilizou exclusivamente dados p&#250;blicos em n&#237;vel populacional, foi isento de aprova&#231;&#227;o por Comit&#234; de &#201;tica em Pesquisa com Seres Humanos e n&#227;o exigiu consentimento informado. Este estudo foi conduzido e reportado em conformidade com as diretrizes <italic>Strengthening the Reporting of Observational Studies in Epidemiology</italic>.</p>
      <sec>
        <title>Envolvimento de pacientes e do p&#250;blico</title>
        <p>Pacientes e membros do p&#250;blico n&#227;o participaram do delineamento, execu&#231;&#227;o, relato ou plano de dissemina&#231;&#227;o desta pesquisa, uma vez que tal participa&#231;&#227;o n&#227;o foi considerada apropriada ou vi&#225;vel.</p>
      </sec>
    </sec>
    <sec sec-type="results">
      <title>Resultados</title>
      <p>Em 1990, o Brasil possu&#237;a 32.751.825 residentes com idade entre 40 e 79 anos, dos quais 51,7% eram mulheres. Entre 1990 e 2040, projeta-se que esse grupo et&#225;rio aumente em 237,8%, acompanhado por um envelhecimento populacional substancial (Figura S1). A propor&#231;&#227;o de adultos com idade entre 75 e 79 anos dever&#225; praticamente dobrar, enquanto a participa&#231;&#227;o de faixas et&#225;rias mais jovens (p.ex., 40-44 anos) dever&#225; diminuir.</p>
      <p>A taxa de mortalidade padronizada por idade por DIC apresentou uma redu&#231;&#227;o substancial entre 1990 e 2021 (Tabela S1, Figura S2), e essa tend&#234;ncia dever&#225; se manter at&#233; 2040 (<xref ref-type="table" rid="t1">Tabela 1</xref>, <xref ref-type="fig" rid="f02">Figura 1</xref>). Embora se prevejam redu&#231;&#245;es em todas as faixas et&#225;rias, a maior queda &#233; esperada entre indiv&#237;duos de 60 a 64 anos (<xref ref-type="table" rid="t1">Tabela 1</xref>, Figura S3, <xref ref-type="fig" rid="f04">Figura 2</xref>).</p>
      <p>
        <table-wrap id="t1">
          <label>Tabela 1</label>
          <caption>
            <title>&#8211; Taxas de mortalidade projetadas (por 100.000 habitantes) por DIC, AVC e DAP no Brasil, por grupos et&#225;rios de 5 anos (40-79 anos), para 2021 (observado), 2030 e 2040 (projetado)</title>
          </caption>
          <table frame="hsides" rules="groups">
            <colgroup>
              <col/>
              <col/>
              <col/>
              <col/>
              <col/>
              <col/>
              <col/>
              <col/>
              <col/>
              <col/>
              <col/>
              <col/>
            </colgroup>
            <thead>
              <tr>
                <th align="left" style="font-weight:normal"> </th>
                <th align="left" style="font-weight:normal"> </th>
                <th rowspan="2">Ano</th>
                <th rowspan="2">Taxa padronizada por idade</th>
                <th colspan="8">Faixa et&#225;ria (anos)</th>
              </tr>
              <tr>
                <th align="left" style="font-weight:normal"> </th>
                <th align="left" style="font-weight:normal"> </th>
                <th>40-44</th>
                <th>45-49</th>
                <th>50-54</th>
                <th>55-59</th>
                <th>60-64</th>
                <th>65-69</th>
                <th>70-74</th>
                <th>75-79</th>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td rowspan="4">
                  <bold>DIC</bold>
                </td>
                <td>Observado</td>
                <td align="center">2021</td>
                <td align="center">118,61 (117,90-119,32)</td>
                <td align="center">21,37 (20,68-22,09)</td>
                <td align="center">40,30 (39,27-41,36)</td>
                <td align="center">70,76 (69,33-72,23)</td>
                <td align="center">112,61 (110,70-114,54)</td>
                <td align="center">173,32 (170,74-175,94)</td>
                <td align="center">249,85 (246,35-253,40)</td>
                <td align="center">354,19 (349,37-359,08)</td>
                <td align="center">516,39 (509,22-523,65)</td>
              </tr>
              <tr>
                <td rowspan="2">Projetado</td>
                <td align="center">2030</td>
                <td align="center">110,76 (72,36-149,16)</td>
                <td align="center">19,88 (13,48-29,54)</td>
                <td align="center">37,16 (25,90-53,67)</td>
                <td align="center">62,84 (44,09-90,21)</td>
                <td align="center">99,91 (70,11-143,41)</td>
                <td align="center">155,50 (109,13-223,17)</td>
                <td align="center">232,25 (162,99-333,31)</td>
                <td align="center">347,29 (243,72-498,40)</td>
                <td align="center">506,23 (355,24-726,46)</td>
              </tr>
              <tr>
                <td align="center">2040</td>
                <td align="center">101,82 (0,36-203,27)</td>
                <td align="center">19,04 (6,38-57,74)</td>
                <td align="center">35,59 (12,40-103,55)</td>
                <td align="center">60,20 (21,46-171,18)</td>
                <td align="center">93,99 (33,83-264,76)</td>
                <td align="center">141,99 (51,21-399,30)</td>
                <td align="center">210,94 (76,06-593,26)</td>
                <td align="center">309,77 (111,71-871,19)</td>
                <td align="center">453,55 (163,55-1275,56)</td>
              </tr>
              <tr>
                <td>Varia&#231;&#227;o percentual relativa</td>
                <td> </td>
                <td align="center">-14,16%</td>
                <td align="center">-10,90%</td>
                <td align="center">-11,69%</td>
                <td align="center">-14,92%</td>
                <td align="center">-16,53%</td>
                <td align="center">-18,08%</td>
                <td align="center">-15,58%</td>
                <td align="center">-12,54%</td>
                <td align="center">-12,17%</td>
              </tr>
              <tr>
                <td> </td>
                <td>EAVP</td>
                <td> </td>
                <td align="center">-0,83 (-0,84a-0,83)</td>
                <td align="center">-1,58 (-1,73a-1,43)</td>
                <td align="center">-1,63 (-1,76a-1,5)</td>
                <td align="center">-1,66 (-1,78a-1,54)</td>
                <td align="center">-1,69 (-1,79a-1,58)</td>
                <td align="center">-1,7 (-1,79a-1,6)</td>
                <td align="center">-1,68 (-1,77a-1,59)</td>
                <td align="center">-1,69 (-1,81a-1,59)</td>
                <td align="center">-1,72 (-1,86a-1,6)</td>
              </tr>
              <tr>
                <td rowspan="4">
                  <bold>AVC</bold>
                </td>
                <td>Observado</td>
                <td align="center">2021</td>
                <td align="center">84,58 (83,99-85,18)</td>
                <td align="center">15,24 (14,66-15,85)</td>
                <td align="center">27,11 (26,27-27,98)</td>
                <td align="center">44,48 (43,35-45,65)</td>
                <td align="center">67,22 (65,75-68,72)</td>
                <td align="center">106,10 (104,09-108,16)</td>
                <td align="center">170,44 (167,56-173,38)</td>
                <td align="center">280,48 (276,18-284,83)</td>
                <td align="center">467,18 (460,37-474,10)</td>
              </tr>
              <tr>
                <td rowspan="2">Projetado</td>
                <td align="center">2030</td>
                <td align="center">78,38 (46,18-110,59)</td>
                <td align="center">13,56 (8,62-21,37)</td>
                <td align="center">23,28 (15,19-35,71)</td>
                <td align="center">37,83 (24,84-57,66)</td>
                <td align="center">58,81 (38,63-89,63)</td>
                <td align="center">94,08 (61,80-143,37)</td>
                <td align="center">155,30 (102,02-236,67)</td>
                <td align="center">273,05 (179,36-416,09)</td>
                <td align="center">466,67 (306,54-711,13)</td>
              </tr>
              <tr>
                <td align="center">2040</td>
                <td align="center">69,90 (0-152,48)</td>
                <td align="center">12,35 (3,44-44,46)</td>
                <td align="center">21,20 (6,13-73,40)</td>
                <td align="center">34,45 (10,18-116,68)</td>
                <td align="center">52,89 (15,77-177,51)</td>
                <td align="center">83,52 (24,96-279,82)</td>
                <td align="center">139,11 (41,57-466,15)</td>
                <td align="center">240,41 (71,84-805,53)</td>
                <td align="center">410,59 (122,69-1375,73)</td>
              </tr>
              <tr>
                <td>Varia&#231;&#227;o percentual relativa</td>
                <td> </td>
                <td align="center">-17,36%</td>
                <td align="center">-18,96%</td>
                <td align="center">-21,80%</td>
                <td align="center">-22,55%</td>
                <td align="center">-21,32%</td>
                <td align="center">-21,28%</td>
                <td align="center">-18,38%</td>
                <td align="center">-14,29%</td>
                <td align="center">-12,11%</td>
              </tr>
              <tr>
                <td> </td>
                <td>EAVP</td>
                <td> </td>
                <td align="center">-1,07 (-1,10a-1,04)</td>
                <td align="center">-2,77 (-3,02a-2,52)</td>
                <td align="center">-2,75 (-2,97a-2,52)</td>
                <td align="center">-2,72 (-2,94a-2,51)</td>
                <td align="center">-2,67 (-2,87a-2,47)</td>
                <td align="center">-2,57 (-2,75a-2,39)</td>
                <td align="center">-2,41 (-2,57a-2,26)</td>
                <td align="center">-2,27 (-2,42a-2,12)</td>
                <td align="center">-2,11 (-2,28a-1,96)</td>
              </tr>
              <tr>
                <td rowspan="4">
                  <bold>DAP</bold>
                </td>
                <td>Observado</td>
                <td align="center">2021</td>
                <td align="center">1,82 (1,73-1,91)</td>
                <td align="center">0,13 (0,09-0,20)</td>
                <td align="center">0,27 (0,20-0,38)</td>
                <td align="center">0,58 (0,46-0,73)</td>
                <td align="center">1,28 (1,09-1,50)</td>
                <td align="center">2,38 (2,10-2,71)</td>
                <td align="center">4,05 (3,62-4,53)</td>
                <td align="center">7,12 (6,46-7,85)</td>
                <td align="center">12,08 (11,03-13,24)</td>
              </tr>
              <tr>
                <td rowspan="2">Projetado</td>
                <td align="center">2030</td>
                <td align="center">2.01 (0,91, 3,10)</td>
                <td align="center">0,12 (0,06-0,24)</td>
                <td align="center">0,26 (0,14-0,48)</td>
                <td align="center">0,56 (0,31-0,98)</td>
                <td align="center">1,17 (0,64-2,01)</td>
                <td align="center">2,34 (1,29-4,00)</td>
                <td align="center">4,52 (2,50-7,72)</td>
                <td align="center">8,44 (4,68-14,42)</td>
                <td align="center">14,92 (8,27-25,49)</td>
              </tr>
              <tr>
                <td align="center">2040</td>
                <td align="center">2,02 (0-5,03)</td>
                <td align="center">0,12 (0,02-0,63)</td>
                <td align="center">0,26 (0,05-1,24)</td>
                <td align="center">0,55 (0,11-2,51)</td>
                <td align="center">1,14 (0,23-5,06)</td>
                <td align="center">2,28 (0,47-9,94)</td>
                <td align="center">4,41 (0,90-19,10)</td>
                <td align="center">8,49 (1,74-36,74)</td>
                <td align="center">16,23 (3,33-70,24)</td>
              </tr>
              <tr>
                <td>Varia&#231;&#227;o percentual relativa</td>
                <td> </td>
                <td align="center">+10,99%</td>
                <td align="center">-7,69%</td>
                <td align="center">-3,70%</td>
                <td align="center">-5,17%</td>
                <td align="center">-10,94%</td>
                <td align="center">-4,20%</td>
                <td align="center">+8,89%</td>
                <td align="center">+19,24%</td>
                <td align="center">+34,35%</td>
              </tr>
              <tr>
                <td> </td>
                <td>EAVP</td>
                <td> </td>
                <td align="center">0,45 (0,30-0,59)</td>
                <td align="center">-0,21 (-0,22a-0,21)</td>
                <td align="center">-0,21 (-0,21a-0,21)</td>
                <td align="center">-0,21 (-0,21a-0,21)</td>
                <td align="center">-0,23 (-0,24a-0,23)</td>
                <td align="center">-0,21 (-0,24a-0,21)</td>
                <td align="center">0,07 (-0,08-0,07)</td>
                <td align="center">0,70 (0,45-0,70)</td>
                <td align="center">1,4 (1,17-1,40)</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN1">
              <p>As taxas padronizadas por idade e espec&#237;ficas por faixa et&#225;ria s&#227;o apresentadas como medianas com intervalo de incerteza (II) para as proje&#231;&#245;es de 2030 e 2040, e como taxas brutas com IC 95% para o ano observado (2021). Tamb&#233;m s&#227;o fornecidas a varia&#231;&#227;o percentual relativa e a EAVP entre 2021 e 2040. DAP: doen&#231;a arterial perif&#233;rica; DIC: doen&#231;a isqu&#234;mica do cora&#231;&#227;o; EAVP: estimativa anual de varia&#231;&#227;o percentual; IC: intervalo de confian&#231;a.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
      </p>
      <p>
        <fig id="f02">
          <label>Figura 1</label>
          <caption>
            <title>&#8211; Proje&#231;&#245;es das taxas de mortalidade padronizadas por idade no Brasil at&#233; 2040. Os pain&#233;is A, B e C apresentam, respectivamente, as taxas de mortalidade padronizadas por idade (por 100.000 habitantes) para DIC, AVC e DAP. As estimativas foram obtidas por meio de modelos bayesianos idade-per&#237;odo-coorte, com base em dados observados de 1990 a 2021. Os pontos pretos representam os valores observados (1990-2021), enquanto os gr&#225;ficos em leque ilustram as estimativas projetadas para 2022-2040. As &#225;reas sombreadas indicam os intervalos de incerteza: as faixas mais escuras representam o intervalo interquartil (25&#186; ao 75&#186; percentil) e as faixas mais claras representam o II 95% (2,5&#186; ao 97,5&#186; percentil). AVC: acidente vascular cerebral; DAP: doen&#231;a arterial perif&#233;rica; DIC: doen&#231;a isqu&#234;mica do cora&#231;&#227;o; II: intervalo de incerteza.</title>
          </caption>
          <graphic xlink:href="1678-4170-abc-122-11-e20250189-50189-gf01.tif"/></fig>
      </p>
      <p>
        <fig id="f03">
          <label>Figura 2</label>
          <caption>
            <title>&#8211; Varia&#231;&#227;o projetada na mortalidade por DIC, AVC e DAP no Brasil por faixa et&#225;ria, 2021-2040. Esta figura apresenta a EAVP nas taxas de mortalidade (por 100.000 habitantes) por DIC, AVC e DAP em faixas et&#225;rias de 5 anos no Brasil, projetadas para o per&#237;odo de 2021 a 2040. As barras representam as estimativas pontuais, e as linhas de erro indicam os IC 95%. Os valores completos da EAVP por faixa et&#225;ria e condi&#231;&#227;o est&#227;o apresentados na Tabela 2. AVC: acidente vascular cerebral; EAVP: estimativa anual de varia&#231;&#227;o percentual; DAP: doen&#231;a arterial perif&#233;rica; DIC: doen&#231;a isqu&#234;mica do cora&#231;&#227;o; IC: intervalo de confian&#231;a.</title>
          </caption>
          <graphic xlink:href="1678-4170-abc-122-11-e20250189-50189-gf02.tif"/></fig>
      </p>
      <p>Entre 1990 e 2021, a mortalidade padronizada por idade por DIC caiu tanto em homens quanto em mulheres, embora as taxas tenham se mantido consistentemente mais altas entre os homens (Tabela S1). Entre 2021 e 2040, projeta-se que a taxa padronizada por idade por DIC diminua 25,33% em homens, mas aumente 4,13% em mulheres (Tabela S2, <xref ref-type="fig" rid="f04">Figura 3</xref> e <xref ref-type="fig" rid="f05">Figura 4</xref>). Conforme mostrado na <xref ref-type="fig" rid="f05">Figura 4</xref>, a diferen&#231;a na mortalidade por DIC entre homens e mulheres dever&#225; se estreitar ao longo do tempo.</p>
      <p>
        <fig id="f04">
          <label>Figura 3</label>
          <caption>
            <title>&#8211; Varia&#231;&#227;o projetada na mortalidade por DIC, AVC e DAP no Brasil at&#233; 2040. Esta figura apresenta a EAVP nas taxas de mortalidade padronizadas por idade (por 100.000 habitantes) para DIC (Painel A), AVC (Painel B) e DAP (Painel C) entre 2021 e 2040. Os resultados s&#227;o apresentados para a popula&#231;&#227;o total, bem como desagregados por sexo (homens e mulheres). AVC: acidente vascular perif&#233;rico; DAP: doen&#231;a arterial perif&#233;rica; DIC: doen&#231;a isqu&#234;mica do cora&#231;&#227;o; EAVP: estimativa anual de varia&#231;&#227;o.</title>
          </caption>
          <graphic xlink:href="1678-4170-abc-122-11-e20250189-50189-gf03.tif"/></fig>
      </p>
      <p>
        <fig id="f05">
          <label>Figura 4</label>
          <caption>
            <title>&#8211; Proje&#231;&#245;es das taxas de mortalidade padronizadas por idade em homens e mulheres no Brasil at&#233; 2040. Os pain&#233;is A, B e C apresentam as taxas de mortalidade padronizadas por idade (por 100.000 habitantes) para doen&#231;a isqu&#234;mica do cora&#231;&#227;o, acidente vascular cerebral e doen&#231;a arterial perif&#233;rica, respectivamente, estratificadas por sexo &#8212; homens (vermelho) e mulheres (azul). Os pontos representam os dados observados de 1990 a 2021, enquanto as linhas correspondem &#224;s proje&#231;&#245;es para 2022&#8211;2040, com base em modelos bayesianos idade-per&#237;odo-coorte. As linhas cont&#237;nuas indicam as estimativas medianas; as linhas tracejadas representam o intervalo interquartil (25&#186; ao 75&#186; percentil); e as linhas pontilhadas refletem o intervalo de incerteza de 95% (2,5&#186; ao 97,5&#186; percentil).</title>
          </caption>
          <graphic xlink:href="1678-4170-abc-122-11-e20250189-50189-gf04.tif"/></fig>
      </p>
      <p>De forma semelhante, a mortalidade padronizada por idade por AVC tamb&#233;m apresentou decl&#237;nio substancial entre 1990 e 2021 (Tabela S3, Figura S2). Espera-se que essa tend&#234;ncia de queda persista at&#233; 2040, com uma redu&#231;&#227;o global de 17,36% no Brasil (<xref ref-type="table" rid="t1">Tabela 1</xref>, <xref ref-type="fig" rid="f02">Figura 1</xref>). Entre os grupos et&#225;rios, a maior queda &#233; projetada para indiv&#237;duos de 50-54 anos (<xref ref-type="table" rid="t1">Tabela 1</xref>, Figura S4, <xref ref-type="fig" rid="f03">Figura 2</xref>).</p>
      <p>De 1990 a 2021, as taxas de mortalidade por AVC diminu&#237;ram em ambos os sexos (Tabela S3). Entre 2021 e 2040, novas redu&#231;&#245;es s&#227;o projetadas; no entanto, a queda ser&#225; significativamente maior entre os homens (30,02%) em compara&#231;&#227;o &#224;s mulheres (4,51%) (Tabela S4, <xref ref-type="fig" rid="f04">Figura 3</xref> e <xref ref-type="fig" rid="f05">Figura 4</xref>). Como ilustrado na <xref ref-type="fig" rid="f05">Figura 4</xref>, a diferen&#231;a entre os sexos na mortalidade por AVC tamb&#233;m dever&#225; se reduzir ao longo do tempo.</p>
      <p>Com rela&#231;&#227;o &#224; DAP, a taxa de mortalidade padronizada por idade apresentou decl&#237;nio inicial entre 1990 e 2015, seguido por um aumento acentuado at&#233; 2021 (Tabela S5, Figura S2). Entre 2021 e 2040, projeta-se que a mortalidade por DAP no Brasil aumente 10,99% (<xref ref-type="table" rid="t1">Tabela 1</xref>, <xref ref-type="fig" rid="f02">Figura 1</xref>). Notadamente, as tend&#234;ncias projetadas variam substancialmente por faixa et&#225;ria. Enquanto se espera uma redu&#231;&#227;o de 7,69% no grupo de 40&#8211;44 anos, a mortalidade dever&#225; aumentar 34,35% entre os indiv&#237;duos de 75 a 79 anos (<xref ref-type="table" rid="t1">Tabela 1</xref>, Figura S5, <xref ref-type="fig" rid="f04">Figura 2</xref>).</p>
      <p>A tend&#234;ncia de queda inicial seguida por aumento acentuado na mortalidade por DAP foi observada tanto em homens quanto em mulheres. Ao longo de todo o per&#237;odo observado, os homens apresentaram taxas consistentemente mais elevadas de mortalidade por DAP (Tabela S5). Entre 2021 e 2040, projeta-se que a mortalidade padronizada por idade por DAP aumente 14,61% em homens e 21,99% em mulheres (Tabela S6, <xref ref-type="fig" rid="f04">Figura 3</xref> e <xref ref-type="fig" rid="f05">Figura 4</xref>).</p>
      <p>A <xref ref-type="fig" rid="f01">Figura Central</xref> fornece um resumo gr&#225;fico dos principais achados do estudo e da abordagem metodol&#243;gica empregada.</p>
    </sec>
    <sec sec-type="discussion">
      <title>Discuss&#227;o</title>
      <p>Examinamos a carga observada de mortalidade por DIC, AVC e DAP entre adultos brasileiros de 1990 a 2021 e ajustamos modelos para projetar estimativas futuras at&#233; 2040. Nossos achados indicam que as taxas de mortalidade padronizadas por idade para DIC e AVC v&#234;m diminuindo de forma cont&#237;nua nas &#250;ltimas 3 d&#233;cadas, com proje&#231;&#245;es que apontam para a manuten&#231;&#227;o dessa tend&#234;ncia. Em contraste, espera-se que a mortalidade por DAP aumente entre 2021 e 2040, com um crescimento desproporcionalmente maior entre as mulheres.</p>
      <p>A redu&#231;&#227;o observada na mortalidade por DIC e AVC desde 1990 est&#225; em conson&#226;ncia com achados pr&#233;vios relatados por Bastos et al., que observaram tend&#234;ncias semelhantes, mas destacaram que as melhorias foram atenuadas em regi&#245;es socioeconomicamente vulner&#225;veis, especialmente nas regi&#245;es Norte e Nordeste do Brasil.<sup><xref ref-type="bibr" rid="B20">20</xref></sup> A Sociedade Brasileira de Cardiologia (SBC) tamb&#233;m relatou redu&#231;&#245;es cont&#237;nuas na mortalidade por DIC e AVC, apesar do impacto adverso da COVID-19 nos desfechos cardiovasculares.<sup><xref ref-type="bibr" rid="B3">3</xref>,<xref ref-type="bibr" rid="B21">21</xref></sup> Proje&#231;&#245;es compar&#225;veis foram publicadas para pa&#237;ses como Estados Unidos, Reino Unido e Jap&#227;o.<sup><xref ref-type="bibr" rid="B9">9</xref>,<xref ref-type="bibr" rid="B10">10</xref>,<xref ref-type="bibr" rid="B22">22</xref></sup> Em conjunto com nossos achados, esse corpo de evid&#234;ncias &#233; encorajador, pois sugere que a mortalidade por DIC e AVC pode continuar a declinar, mesmo diante do expressivo envelhecimento populacional.</p>
      <p>No entanto, nosso estudo tamb&#233;m revelou que a queda projetada na mortalidade por AVC ser&#225; consideravelmente menor entre os idosos. Um estudo anterior com dados dos EUA relatou redu&#231;&#245;es m&#237;nimas na mortalidade por AVC entre indiv&#237;duos com 65-74, 75-84 e 85 anos ou mais, de ambos os sexos.<sup><xref ref-type="bibr" rid="B9">9</xref></sup> Esses achados ressaltam a necessidade de estrat&#233;gias espec&#237;ficas de preven&#231;&#227;o e cuidados com o AVC nas popula&#231;&#245;es idosas. &#201; importante destacar que DIC e AVC compartilham diversos fatores de risco modific&#225;veis. Uma meta-an&#225;lise recente envolvendo 50.000 pacientes mostrou que aproximadamente um ter&#231;o dos pacientes com AVC agudo tamb&#233;m apresenta DIC e possui risco aumentado de infarto do mioc&#225;rdio dentro de 1 ano ap&#243;s o AVC.<sup><xref ref-type="bibr" rid="B23">23</xref></sup></p>
      <p>No Brasil, o cuidado agudo do AVC &#233; dificultado por popula&#231;&#245;es rurais extensas e pela distribui&#231;&#227;o desigual dos recursos de sa&#250;de. Embora unidades dedicadas ao atendimento do AVC e programas de fibrin&#243;lise tenham sido implementados em diversos centros metropolitanos, o acesso permanece limitado em regi&#245;es rurais e desassistidas.<sup><xref ref-type="bibr" rid="B24">24</xref></sup> Embora as pol&#237;ticas p&#250;blicas de sa&#250;de existentes tenham contribu&#237;do para a melhora da mortalidade por DIC e AVC, esfor&#231;os adicionais s&#227;o necess&#225;rios para consolidar esses avan&#231;os &#8212; especialmente diante do r&#225;pido envelhecimento da popula&#231;&#227;o brasileira.</p>
      <p>Nosso estudo tamb&#233;m destaca 2 aspectos particularmente preocupantes: (i) a crescente carga de mortalidade por DAP no Brasil e (ii) diferen&#231;as significativas entre os sexos nas taxas projetadas de mortalidade por DIC, AVC e DAP. Segundo o GBD, a carga global de DAP aumentou 72% entre 1990 e 2019.<sup><xref ref-type="bibr" rid="B25">25</xref></sup> Proje&#231;&#245;es do <italic>Institute for Health Metrics and Evaluation</italic> &#8212; respons&#225;vel pelo GBD &#8212; indicam que os pa&#237;ses de baixa e m&#233;dia renda dever&#227;o arcar com uma parcela desproporcionalmente maior dessa carga.<sup><xref ref-type="bibr" rid="B2">2</xref></sup> A DAP avan&#231;ada est&#225; associada a elevadas taxas de amputa&#231;&#227;o de membros inferiores, baixa qualidade de vida, morbidade substancial e mortalidade elevada em 5 a 10 anos.<sup><xref ref-type="bibr" rid="B27">27</xref>,<xref ref-type="bibr" rid="B28">28</xref></sup> Esses desfechos ressaltam a urg&#234;ncia de implementa&#231;&#227;o de pol&#237;ticas p&#250;blicas voltadas para a detec&#231;&#227;o precoce e o manejo adequado da DAP.</p>
      <p>A segunda quest&#227;o-chave identificada refere-se &#224; acentuada disparidade nos desfechos cardiovasculares entre os sexos. Um estudo realizado na Espanha observou que, em compara&#231;&#227;o aos homens, as mulheres apresentaram maiores atrasos no diagn&#243;stico e tratamento do infarto agudo do mioc&#225;rdio.<sup><xref ref-type="bibr" rid="B28">28</xref></sup> No contexto da DAP, os desfechos da cirurgia vascular tamb&#233;m s&#227;o piores para as mulheres, que t&#234;m maior probabilidade de se apresentar com isquemia aguda de membros.<sup><xref ref-type="bibr" rid="B26">26</xref>,<xref ref-type="bibr" rid="B29">29</xref></sup> Segundo o relat&#243;rio de 2023 do Minist&#233;rio da Sa&#250;de do Brasil e da SBC, as taxas de obesidade s&#227;o mais elevadas entre mulheres do que entre homens, e as mulheres t&#234;m 44% mais probabilidade de apresentar dislipidemia.<sup><xref ref-type="bibr" rid="B3">3</xref></sup> A maior preval&#234;ncia e mortalidade por DAP entre mulheres pode tamb&#233;m refletir a presen&#231;a de aterosclerose n&#227;o diagnosticada ou n&#227;o tratada, condi&#231;&#227;o sabidamente mais prevalente entre mulheres. Em conjunto, esses achados refor&#231;am a necessidade urgente de iniciativas de sa&#250;de direcionadas &#224; redu&#231;&#227;o das disparidades de sexo nos desfechos cardiovasculares.</p>
      <p>Em 2011, o Minist&#233;rio da Sa&#250;de do Brasil lan&#231;ou um plano estrat&#233;gico de 10 anos para redu&#231;&#227;o das taxas de doen&#231;as cr&#244;nicas n&#227;o transmiss&#237;veis. Desde ent&#227;o, o pa&#237;s obteve conquistas importantes, incluindo uma redu&#231;&#227;o de 30% na preval&#234;ncia de tabagismo e um aumento de 10% na pr&#225;tica de atividade f&#237;sica entre adultos.<sup><xref ref-type="bibr" rid="B30">30</xref></sup> Esses avan&#231;os s&#227;o expressivos, considerando que aproximadamente 70% da carga total de DCVs &#233; atribu&#237;vel a fatores de risco modific&#225;veis.<sup><xref ref-type="bibr" rid="B2">2</xref></sup> No entanto, como observado em muitos outros pa&#237;ses, o Brasil continua enfrentando aumento nas taxas de obesidade em adultos, bem como maior preval&#234;ncia de hipertens&#227;o, diabetes e dislipidemia.<sup><xref ref-type="bibr" rid="B30">30</xref></sup></p>
      <p>Em resposta, o governo brasileiro &#8212; em parceria com a SBC e outras sociedades m&#233;dicas &#8212; apresentou, em 2023, um novo plano nacional de enfrentamento das DCVs, atualmente em an&#225;lise pelo Senado.<sup><xref ref-type="bibr" rid="B31">31</xref></sup> Essa proposta legislativa busca enfrentar os desafios atuais por meio da implementa&#231;&#227;o de interven&#231;&#245;es direcionadas e da cria&#231;&#227;o de um fundo federal dedicado ao combate das DCV. A aloca&#231;&#227;o proposta para esse fundo inclui: 30% para pesquisa relacionada &#224;s DCV; 15% para campanhas p&#250;blicas de conscientiza&#231;&#227;o sobre fatores de risco cardiovasculares; 30% para capacita&#231;&#227;o de profissionais de sa&#250;de, com &#234;nfase na aten&#231;&#227;o prim&#225;ria; e 15% para programas voltados &#224; redu&#231;&#227;o do tabagismo, do consumo de &#225;lcool e de outros fatores de risco modific&#225;veis. Al&#233;m disso, 10% do fundo seriam administrados pelo Conselho Federal de Medicina para apoiar a forma&#231;&#227;o especializada em cuidados cardiovasculares. Tais iniciativas podem contribuir para reverter as tend&#234;ncias recentes de subfinanciamento do sistema p&#250;blico de sa&#250;de no Brasil.<sup><xref ref-type="bibr" rid="B32">32</xref></sup></p>
      <p>Melhorar a ades&#227;o ao tratamento medicamentoso e ampliar o acesso aos cuidados &#8212; especialmente por meio da forma&#231;&#227;o e distribui&#231;&#227;o geogr&#225;fica de profissionais de sa&#250;de capacitados em cardiologia preventiva &#8212; tamb&#233;m s&#227;o estrat&#233;gias fundamentais para enfrentar de forma eficaz a carga nacional de DCV.<sup><xref ref-type="bibr" rid="B5">5</xref>,<xref ref-type="bibr" rid="B33">33</xref>,<xref ref-type="bibr" rid="B34">34</xref></sup></p>
      <p>Al&#233;m dos fatores de risco cardiovasculares tradicionais, &#233; essencial reconhecer o papel das exposi&#231;&#245;es ambientais, como a polui&#231;&#227;o do ar por part&#237;culas finas, que foi associada causalmente &#224;s DCV. De forma encorajadora, dados recentes mostram que a mortalidade atribu&#237;vel &#224; polui&#231;&#227;o do ar no Brasil diminuiu entre 2010 e 2019.<sup><xref ref-type="bibr" rid="B35">35</xref></sup> Contudo, o mesmo estudo relatou que os n&#237;veis de polui&#231;&#227;o em determinadas regi&#245;es permaneceram m&#250;ltiplas vezes acima dos limites recomendados pela OMS.<sup><xref ref-type="bibr" rid="B35">35</xref></sup> Assim, os futuros esfor&#231;os em pol&#237;ticas p&#250;blicas devem n&#227;o apenas manter o foco nos fatores de risco convencionais para DCV, mas tamb&#233;m se expandir para contemplar os determinantes ambientais da sa&#250;de cardiovascular.</p>
      <p>Por fim, conforme amplamente discutido na comunidade cardiol&#243;gica, o desenvolvimento de diretrizes de cardiologia preventiva especificamente voltadas &#224;s mulheres constitui um passo crucial para reduzir as disparidades de sexo identificadas em nosso estudo.<sup><xref ref-type="bibr" rid="B36">36</xref>-<xref ref-type="bibr" rid="B39">39</xref></sup></p>
      <sec>
        <title>Pontos fortes e limita&#231;&#245;es</title>
        <p>Este estudo apresenta v&#225;rias limita&#231;&#245;es que devem ser reconhecidas. Tanto as taxas de eventos quanto as estimativas populacionais de meio de ano foram obtidas a partir do conjunto de dados do GBD 2021. Embora esses dados tenham como fonte primeira o SIM, o GBD aplica seus pr&#243;prios procedimentos de modelagem. Como resultado, nossos achados podem divergir de estudos que extraem diretamente os dados da fonte original.<sup><xref ref-type="bibr" rid="B40">40</xref>,<xref ref-type="bibr" rid="B41">41</xref></sup> Ainda assim, por harmonizar os dados entre pa&#237;ses, o GBD permite que nossos resultados sejam mais facilmente compar&#225;veis a estudos internacionais.</p>
        <p>Embora o SIM realize rotineiramente verifica&#231;&#245;es de qualidade para garantir a precis&#227;o dos dados, os atestados de &#243;bito permanecem como principal fonte de informa&#231;&#227;o sobre mortalidade. A acur&#225;cia desses registros pode variar, especialmente em regi&#245;es rurais com recursos limitados. No entanto, a metodologia do GBD &#233; especificamente desenvolvida para lidar com quest&#245;es de completude e classifica&#231;&#227;o incorreta dos dados.</p>
        <p>Nosso estudo n&#227;o considera fatores de risco em n&#237;vel individual ou populacional. Tend&#234;ncias futuras na mortalidade por DIC, AVC e DAP podem ser significativamente influenciadas por altera&#231;&#245;es nesses fatores. Embora estrat&#233;gias mais agressivas de mitiga&#231;&#227;o possam reduzir as taxas de eventos no futuro, as tend&#234;ncias atuais &#8212; como o aumento da preval&#234;ncia de obesidade, diabetes e tabagismo &#8212; podem potencialmente resultar em mortalidade ainda mais elevada do que a projetada.</p>
        <p>Utilizamos modelos bayesianos IPC para projetar estimativas futuras de mortalidade. Como toda abordagem de modelagem, esses modelos requerem certas premissas. Embora n&#227;o se possa descartar a possibilidade de especifica&#231;&#227;o inadequada, apresentamos II 95% para contemplar tais limita&#231;&#245;es. Ademais, os desfechos em sa&#250;de p&#250;blica s&#227;o influenciados por uma ampla gama de fatores &#8212; incluindo mudan&#231;as pol&#237;ticas, culturais, migrat&#243;rias e ambientais &#8212; muitos dos quais n&#227;o podem ser totalmente capturados pelos modelos matem&#225;ticos utilizados neste estudo.</p>
      </sec>
    </sec>
    <sec sec-type="conclusions">
      <title>Conclus&#227;o</title>
      <p>Com base nos dados observados de 1990 a 2021, projeta-se que a mortalidade padronizada por idade por DIC e AVC no Brasil continue em decl&#237;nio at&#233; 2040. Em contraste, espera-se que a mortalidade padronizada por idade atribu&#237;vel &#224; DAP aumente substancialmente ao longo do mesmo per&#237;odo. Enquanto as redu&#231;&#245;es projetadas na mortalidade por DIC e AVC ser&#227;o mais acentuadas entre os homens, o aumento na mortalidade por DAP dever&#225; ser consideravelmente maior entre as mulheres. Esses achados ressaltam a necessidade urgente de interven&#231;&#245;es sustentadas e direcionadas em sa&#250;de p&#250;blica, com o objetivo de reduzir disparidades cardiovasculares, ampliar a conscientiza&#231;&#227;o e melhorar o acesso equitativo a cuidados embasados em evid&#234;ncias em todo o Brasil.</p>
    </sec>
    <sec sec-type="supplementary-material">
      <title>*Material suplementar</title>
      <supplementary-material id="suppl01">
        <p>Para informa&#231;&#227;o adicional, por favor, clique aqui.<ext-link ext-link-type="uri" xlink:href="https://abccardiol.org/supplementary-material/2025/12212/2025-0189_final_supplemental_section.pdf">https://abccardiol.org/supplementary-material/2025/12212/2025-0189_final_supplemental_section.pdf</ext-link> </p>
        <media mime-subtype="pdf" mimetype="application" xlink:href="https://minio.scielo.br/documentstore/1678-4170/VBdrFFYqYbrqWKfJ65rKdPw/0b0f9e5209bc9501e18a86ca8d4e8a4dc3fb4518.pdf"/>
      </supplementary-material>
    </sec>
  </body>
  <back>
    <ref-list>
      <title>Refer&#234;ncias</title>
      <ref id="B1">
        <label>1</label>
        <mixed-citation>1. Barquera S, Pedroza-Tob&#237;as A, Medina C, Hern&#225;ndez-Barrera L, Bibbins-Domingo K, Lozano R, et al. Global Overview of the Epidemiology of Atherosclerotic Cardiovascular Disease. Arch Med Res. 2015;46(5):328-38. doi: 10.1016/j.arcmed.2015.06.006.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Barquera</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Pedroza-Tob&#237;as</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Medina</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Hern&#225;ndez-Barrera</surname>
              <given-names>L</given-names>
            </name>
            <name>
              <surname>Bibbins-Domingo</surname>
              <given-names>K</given-names>
            </name>
            <name>
              <surname>Lozano</surname>
              <given-names>R</given-names>
            </name>
            <etal>et al</etal>
          </person-group>
          <article-title>Global Overview of the Epidemiology of Atherosclerotic Cardiovascular Disease</article-title>
          <source>Arch Med Res</source>
          <year>2015</year>
          <volume>46</volume>
          <issue>5</issue>
          <fpage>328</fpage>
          <lpage>338</lpage>
          <pub-id pub-id-type="doi">10.1016/j.arcmed.2015.06.006</pub-id>
        </element-citation>
      </ref>
      <ref id="B2">
        <label>2</label>
        <mixed-citation>2. GBD 2019 Peripheral Artery Disease Collaborators. Global Burden of Peripheral Artery Disease and Its Risk Factors, 1990-2019: A Systematic Analysis for the Global Burden of Disease Study 2019. Lancet Glob Health. 2023;11(10):e1553-65. doi: 10.1016/S2214-109X(23)00355-8.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <collab>GBD 2019 Peripheral Artery Disease Collaborators</collab>
          </person-group>
          <article-title>Global Burden of Peripheral Artery Disease and Its Risk Factors, 1990-2019: A Systematic Analysis for the Global Burden of Disease Study 2019</article-title>
          <source>Lancet Glob Health</source>
          <year>2023</year>
          <volume>11</volume>
          <issue>10</issue>
          <fpage>e1553</fpage>
          <lpage>e1565</lpage>
          <pub-id pub-id-type="doi">10.1016/S2214-109X(23)00355-8</pub-id>
        </element-citation>
      </ref>
      <ref id="B3">
        <label>3</label>
        <mixed-citation>3. Oliveira GMM, Brant LCC, Polanczyk CA, Malta DC, Biolo A, Nascimento BR, et al. Cardiovascular Statistics - Brazil 2023. Arq Bras Cardiol. 2024;121(2):e20240079. doi: 10.36660/abc.20240079.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Oliveira</surname>
              <given-names>GMM</given-names>
            </name>
            <name>
              <surname>Brant</surname>
              <given-names>LCC</given-names>
            </name>
            <name>
              <surname>Polanczyk</surname>
              <given-names>CA</given-names>
            </name>
            <name>
              <surname>Malta</surname>
              <given-names>DC</given-names>
            </name>
            <name>
              <surname>Biolo</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Nascimento</surname>
              <given-names>BR</given-names>
            </name>
            <etal>et al</etal>
          </person-group>
          <article-title>Cardiovascular Statistics - Brazil 2023</article-title>
          <source>Arq Bras Cardiol</source>
          <year>2024</year>
          <volume>121</volume>
          <issue>2</issue>
          <elocation-id>e20240079</elocation-id>
          <pub-id pub-id-type="doi">10.36660/abc.20240079</pub-id>
        </element-citation>
      </ref>
      <ref id="B4">
        <label>4</label>
        <mixed-citation>4. Oliveira GMM, Brant LCC, Polanczyk CA, Malta DC, Biolo A, Nascimento BR, et al. Cardiovascular Statistics - Brazil 2021. Arq Bras Cardiol. 2022;118(1):115-373. doi: 10.36660/abc.20211012.</mixed-citation>
        <element-citation publication-type="report">
          <person-group person-group-type="author">
            <name>
              <surname>Oliveira</surname>
              <given-names>GMM</given-names>
            </name>
            <name>
              <surname>Brant</surname>
              <given-names>LCC</given-names>
            </name>
            <name>
              <surname>Polanczyk</surname>
              <given-names>CA</given-names>
            </name>
            <name>
              <surname>Malta</surname>
              <given-names>DC</given-names>
            </name>
            <name>
              <surname>Biolo</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Nascimento</surname>
              <given-names>BR</given-names>
            </name>
            <etal>et al</etal>
          </person-group>
          <article-title>Cardiovascular Statistics - Brazil 2021</article-title>
          <source>Arq Bras Cardiol</source>
          <year>2022</year>
          <volume>118</volume>
          <issue>1</issue>
          <fpage>115</fpage>
          <lpage>373</lpage>
          <pub-id pub-id-type="doi">10.36660/abc.20211012</pub-id>
        </element-citation>
      </ref>
      <ref id="B5">
        <label>5</label>
        <mixed-citation>5. Berwanger O, Santo K. Cardiovascular Care in Brazil: Current Status, Challenges, and Opportunities. Circulation. 2022;146(6):435-7. doi: 10.1161/CIRCULATIONAHA.122.059320.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Berwanger</surname>
              <given-names>O</given-names>
            </name>
            <name>
              <surname>Santo</surname>
              <given-names>K</given-names>
            </name>
          </person-group>
          <article-title>Cardiovascular Care in Brazil: Current Status, Challenges, and Opportunities</article-title>
          <source>Circulation</source>
          <year>2022</year>
          <volume>146</volume>
          <issue>6</issue>
          <fpage>435</fpage>
          <lpage>437</lpage>
          <pub-id pub-id-type="doi">10.1161/CIRCULATIONAHA.122.059320</pub-id>
        </element-citation>
      </ref>
      <ref id="B6">
        <label>6</label>
        <mixed-citation>6. Duncan BB, Cousin E, Naghavi M, Afshin A, Fran&#231;a EB, Passos VMA, et al. The Burden of Diabetes and Hyperglycemia in Brazil: A Global Burden of Disease Study 2017. Popul Health Metr. 2020;18(Suppl 1):9. doi: 10.1186/s12963-020-00209-0.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Duncan</surname>
              <given-names>BB</given-names>
            </name>
            <name>
              <surname>Cousin</surname>
              <given-names>E</given-names>
            </name>
            <name>
              <surname>Naghavi</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Afshin</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Fran&#231;a</surname>
              <given-names>EB</given-names>
            </name>
            <name>
              <surname>Passos</surname>
              <given-names>VMA</given-names>
            </name>
            <etal>et al</etal>
          </person-group>
          <article-title>The Burden of Diabetes and Hyperglycemia in Brazil: A Global Burden of Disease Study 2017</article-title>
          <source>Popul Health Metr</source>
          <year>2020</year>
          <volume>18</volume>
          <supplement>Suppl 1</supplement>
          <size units="pages">9</size>
          <pub-id pub-id-type="doi">10.1186/s12963-020-00209-0</pub-id>
        </element-citation>
      </ref>
      <ref id="B7">
        <label>7</label>
        <mixed-citation>7. Menicucci TM. The History of the Public Health Reform in Brazil and of the Sistema &#218;nico de Sa&#250;de: Changes, Continuities, and the Current Agenda. Hist Cienc Saude Manguinhos. 2014;21(1):77-92. doi: 10.1590/s0104-59702014000100004.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Menicucci</surname>
              <given-names>TM</given-names>
            </name>
          </person-group>
          <article-title>The History of the Public Health Reform in Brazil and of the Sistema &#218;nico de Sa&#250;de: Changes, Continuities, and the Current Agenda</article-title>
          <source>Hist Cienc Saude Manguinhos</source>
          <year>2014</year>
          <volume>21</volume>
          <issue>1</issue>
          <fpage>77</fpage>
          <lpage>92</lpage>
          <pub-id pub-id-type="doi">10.1590/s0104-59702014000100004</pub-id>
        </element-citation>
      </ref>
      <ref id="B8">
        <label>8</label>
        <mixed-citation>8. Fonseca EM, Shadlen KC. Promoting and Regulating Generic Medicines: Brazil in Comparative Perspective. Rev Panam Salud Publica. 2017;41:e5. doi: 10.26633/RPSP.2017.5.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Fonseca</surname>
              <given-names>EM</given-names>
            </name>
            <name>
              <surname>Shadlen</surname>
              <given-names>KC</given-names>
            </name>
          </person-group>
          <article-title>Promoting and Regulating Generic Medicines: Brazil in Comparative Perspective</article-title>
          <source>Rev Panam Salud Publica</source>
          <year>2017</year>
          <volume>41</volume>
          <elocation-id>e5</elocation-id>
          <pub-id pub-id-type="doi">10.26633/RPSP.2017.5</pub-id>
        </element-citation>
      </ref>
      <ref id="B9">
        <label>9</label>
        <mixed-citation>9. Pearson-Stuttard J, Guzman-Castillo M, Penalvo JL, Rehm CD, Afshin A, Danaei G, et al. Modeling Future Cardiovascular Disease Mortality in the United States: National Trends and Racial and Ethnic Disparities. Circulation. 2016;133(10):967-78. doi: 10.1161/CIRCULATIONAHA.115.019904.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Pearson-Stuttard</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Guzman-Castillo</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Penalvo</surname>
              <given-names>JL</given-names>
            </name>
            <name>
              <surname>Rehm</surname>
              <given-names>CD</given-names>
            </name>
            <name>
              <surname>Afshin</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Danaei</surname>
              <given-names>G</given-names>
            </name>
            <etal>et al</etal>
          </person-group>
          <article-title>Modeling Future Cardiovascular Disease Mortality in the United States: National Trends and Racial and Ethnic Disparities</article-title>
          <source>Circulation</source>
          <year>2016</year>
          <volume>133</volume>
          <issue>10</issue>
          <fpage>967</fpage>
          <lpage>978</lpage>
          <pub-id pub-id-type="doi">10.1161/CIRCULATIONAHA.115.019904</pub-id>
        </element-citation>
      </ref>
      <ref id="B10">
        <label>10</label>
        <mixed-citation>10. Kiyoshige E, Ogata S, O'Flaherty M, Capewell S, Takegami M, Iihara K, et al. Projections of Future Coronary Heart Disease and Stroke Mortality in Japan Until 2040: A Bayesian Age-Period-Cohort Analysis. Lancet Reg Health West Pac. 2022;31:100637. doi: 10.1016/j.lanwpc.2022.100637.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Kiyoshige</surname>
              <given-names>E</given-names>
            </name>
            <name>
              <surname>Ogata</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>O'Flaherty</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Capewell</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Takegami</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Iihara</surname>
              <given-names>K</given-names>
            </name>
            <etal>et al</etal>
          </person-group>
          <article-title>Projections of Future Coronary Heart Disease and Stroke Mortality in Japan Until 2040: A Bayesian Age-Period-Cohort Analysis</article-title>
          <source>Lancet Reg Health West Pac</source>
          <year>2022</year>
          <volume>31</volume>
          <size units="pages">100637</size>
          <pub-id pub-id-type="doi">10.1016/j.lanwpc.2022.100637</pub-id>
        </element-citation>
      </ref>
      <ref id="B11">
        <label>11</label>
        <mixed-citation>11. Institute for Health Metrics and Evaluation. GBD Results [Internet]. Seattle: IHME; 2023 [cited 2025 Sep 30]. Available from: <ext-link ext-link-type="uri" xlink:href="https://vizhub.healthdata.org/gbd-results">https://vizhub.healthdata.org/gbd-results</ext-link>.</mixed-citation>
        <element-citation publication-type="webpage">
          <person-group person-group-type="author">
            <collab>Institute for Health Metrics and Evaluation</collab>
          </person-group>
          <source>GBD Results</source>
          <comment>Internet</comment>
          <publisher-loc>Seattle</publisher-loc>
          <publisher-name>IHME</publisher-name>
          <year>2023</year>
          <date-in-citation content-type="cited-date">cited 2025 Sep 30</date-in-citation>
          <comment>
            <ext-link ext-link-type="uri" xlink:href="https://vizhub.healthdata.org/gbd-results">https://vizhub.healthdata.org/gbd-results</ext-link>
          </comment>
        </element-citation>
      </ref>
      <ref id="B12">
        <label>12</label>
        <mixed-citation>12. Institute for Health Metrics and Evaluation. GBD History [Internet]. Seattle: IHME; 2014 [cited 2025 Sep 30]. Available from: <ext-link ext-link-type="uri" xlink:href="https://www.healthdata.org/gbd/about/history">https://www.healthdata.org/gbd/about/history</ext-link>.</mixed-citation>
        <element-citation publication-type="webpage">
          <person-group person-group-type="author">
            <collab>Institute for Health Metrics and Evaluation</collab>
          </person-group>
          <source>GBD History</source>
          <comment>Internet</comment>
          <publisher-loc>Seattle</publisher-loc>
          <publisher-name>IHME</publisher-name>
          <year>2014</year>
          <date-in-citation content-type="cited-date">cited 2025 Sep 30</date-in-citation>
          <comment>
            <ext-link ext-link-type="uri" xlink:href="https://www.healthdata.org/gbd/about/history">https://www.healthdata.org/gbd/about/history</ext-link>
          </comment>
        </element-citation>
      </ref>
      <ref id="B13">
        <label>13</label>
        <mixed-citation>13. Roth GA, Mensah GA, Johnson CO, Addolorato G, Ammirati E, Baddour LM, et al. Global Burden of Cardiovascular Diseases and Risk Factors, 1990-2019: Update from the GBD 2019 Study. J Am Coll Cardiol. 2020;76(25):2982-3021. doi: 10.1016/j.jacc.2020.11.010.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Roth</surname>
              <given-names>GA</given-names>
            </name>
            <name>
              <surname>Mensah</surname>
              <given-names>GA</given-names>
            </name>
            <name>
              <surname>Johnson</surname>
              <given-names>CO</given-names>
            </name>
            <name>
              <surname>Addolorato</surname>
              <given-names>G</given-names>
            </name>
            <name>
              <surname>Ammirati</surname>
              <given-names>E</given-names>
            </name>
            <name>
              <surname>Baddour</surname>
              <given-names>LM</given-names>
            </name>
            <etal>et al</etal>
          </person-group>
          <article-title>Global Burden of Cardiovascular Diseases and Risk Factors, 1990-2019: Update from the GBD 2019 Study</article-title>
          <source>J Am Coll Cardiol</source>
          <year>2020</year>
          <volume>76</volume>
          <issue>25</issue>
          <fpage>2982</fpage>
          <lpage>3021</lpage>
          <pub-id pub-id-type="doi">10.1016/j.jacc.2020.11.010</pub-id>
        </element-citation>
      </ref>
      <ref id="B14">
        <label>14</label>
        <mixed-citation>14. Institute for Health Metrics and Evaluation. Global Burden of Disease Study 2019 (GBD 2019) Data Input Sources Tool [Internet]. Seattle: IHME; 2019 [cited 2025 Sep 30]. Available from: <ext-link ext-link-type="uri" xlink:href="https://ghdx.healthdata.org/gbd-2019/data-input-sources?components=4&amp;causes=491&amp;locations=135">https://ghdx.healthdata.org/gbd-2019/data-input-sources?components=4&amp;causes=491&amp;locations=135</ext-link>.</mixed-citation>
        <element-citation publication-type="webpage">
          <person-group person-group-type="author">
            <collab>Institute for Health Metrics and Evaluation</collab>
          </person-group>
          <source>Global Burden of Disease Study 2019 (GBD 2019) Data Input Sources Tool</source>
          <comment>Internet</comment>
          <publisher-loc>Seattle</publisher-loc>
          <publisher-name>IHME</publisher-name>
          <year>2019</year>
          <date-in-citation content-type="cited-date">cited 2025 Sep 30</date-in-citation>
          <comment>
            <ext-link ext-link-type="uri" xlink:href="https://ghdx.healthdata.org/gbd-2019/data-input-sources?components=4&amp;causes=491&amp;locations=135">https://ghdx.healthdata.org/gbd-2019/data-input-sources?components=4&amp;causes=491&amp;locations=135</ext-link>
          </comment>
        </element-citation>
      </ref>
      <ref id="B15">
        <label>15</label>
        <mixed-citation>15. Institute for Health Metrics and Evaluation. Global Fertility, Mortality, Migration, and Population Forecasts 2017-2100 [Internet]. Seattle: IHME; 2020 [cited 2025 Sep 30]. Available from: <ext-link ext-link-type="uri" xlink:href="http://ghdx.healthdata.org/record/ihme-data/global-population-forecasts-2017-2100">http://ghdx.healthdata.org/record/ihme-data/global-population-forecasts-2017-2100</ext-link>.</mixed-citation>
        <element-citation publication-type="webpage">
          <person-group person-group-type="author">
            <collab>Institute for Health Metrics and Evaluation</collab>
          </person-group>
          <source>Global Fertility, Mortality, Migration, and Population Forecasts 2017-2100</source>
          <comment>Internet</comment>
          <publisher-loc>Seattle</publisher-loc>
          <publisher-name>IHME</publisher-name>
          <year>2020</year>
          <date-in-citation content-type="cited-date">cited 2025 Sep 30</date-in-citation>
          <comment>
            <ext-link ext-link-type="uri" xlink:href="http://ghdx.healthdata.org/record/ihme-data/global-population-forecasts-2017-2100">http://ghdx.healthdata.org/record/ihme-data/global-population-forecasts-2017-2100</ext-link>
          </comment>
        </element-citation>
      </ref>
      <ref id="B16">
        <label>16</label>
        <mixed-citation>16. Vollset SE, Goren E, Yuan CW, Cao J, Smith AE, Hsiao T, et al. Fertility, Mortality, Migration, and Population Scenarios for 195 Countries and Territories from 2017 to 2100: A Forecasting Analysis for the Global Burden of Disease Study. Lancet. 2020;396(10258):1285-306. doi: 10.1016/S0140-6736(20)30677-2.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Vollset</surname>
              <given-names>SE</given-names>
            </name>
            <name>
              <surname>Goren</surname>
              <given-names>E</given-names>
            </name>
            <name>
              <surname>Yuan</surname>
              <given-names>CW</given-names>
            </name>
            <name>
              <surname>Cao</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Smith</surname>
              <given-names>AE</given-names>
            </name>
            <name>
              <surname>Hsiao</surname>
              <given-names>T</given-names>
            </name>
            <etal>et al</etal>
          </person-group>
          <article-title>Fertility, Mortality, Migration, and Population Scenarios for 195 Countries and Territories from 2017 to 2100: A Forecasting Analysis for the Global Burden of Disease Study</article-title>
          <source>Lancet</source>
          <year>2020</year>
          <volume>396</volume>
          <issue>10258</issue>
          <fpage>1285</fpage>
          <lpage>1306</lpage>
          <pub-id pub-id-type="doi">10.1016/S0140-6736(20)30677-2</pub-id>
        </element-citation>
      </ref>
      <ref id="B17">
        <label>17</label>
        <mixed-citation>17. Perea LME, Antunes JLF, Peres MA. Approaches to the Problem of Nonidentifiability in the Age-Period-Cohort Models in the Analysis of Cancer Mortality: A Scoping Review. Eur J Cancer Prev. 2022;31(1):93-103. doi: 10.1097/CEJ.0000000000000713.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Perea</surname>
              <given-names>LME</given-names>
            </name>
            <name>
              <surname>Antunes</surname>
              <given-names>JLF</given-names>
            </name>
            <name>
              <surname>Peres</surname>
              <given-names>MA</given-names>
            </name>
          </person-group>
          <article-title>Approaches to the Problem of Nonidentifiability in the Age-Period-Cohort Models in the Analysis of Cancer Mortality: A Scoping Review</article-title>
          <source>Eur J Cancer Prev</source>
          <year>2022</year>
          <volume>31</volume>
          <issue>1</issue>
          <fpage>93</fpage>
          <lpage>103</lpage>
          <pub-id pub-id-type="doi">10.1097/CEJ.0000000000000713</pub-id>
        </element-citation>
      </ref>
      <ref id="B18">
        <label>18</label>
        <mixed-citation>18. Riebler A, Held L. Projecting the Future Burden of Cancer: Bayesian Age-Period-Cohort Analysis with Integrated Nested Laplace Approximations. Biom J. 2017;59(3):531-49. doi: 10.1002/bimj.201500263.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Riebler</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Held</surname>
              <given-names>L</given-names>
            </name>
          </person-group>
          <article-title>Projecting the Future Burden of Cancer: Bayesian Age-Period-Cohort Analysis with Integrated Nested Laplace Approximations</article-title>
          <source>Biom J</source>
          <year>2017</year>
          <volume>59</volume>
          <issue>3</issue>
          <fpage>531</fpage>
          <lpage>549</lpage>
          <pub-id pub-id-type="doi">10.1002/bimj.201500263</pub-id>
        </element-citation>
      </ref>
      <ref id="B19">
        <label>19</label>
        <mixed-citation>19. Rue H, Martino S, Chopin N. Approximate Bayesian Inference for Latent Gaussian Models by Using Integrated Nested Laplace Approximations. J R Stat Soc Ser B Stat Methodol. 2009;71(2):319-92. doi: 10.1111/j.1467-9868.2008.00700.x.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Rue</surname>
              <given-names>H</given-names>
            </name>
            <name>
              <surname>Martino</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Chopin</surname>
              <given-names>N</given-names>
            </name>
          </person-group>
          <article-title>Approximate Bayesian Inference for Latent Gaussian Models by Using Integrated Nested Laplace Approximations</article-title>
          <source>J R Stat Soc Ser B Stat Methodol</source>
          <year>2009</year>
          <volume>71</volume>
          <issue>2</issue>
          <fpage>319</fpage>
          <lpage>392</lpage>
          <pub-id pub-id-type="doi">10.1111/j.1467-9868.2008.00700.x</pub-id>
        </element-citation>
      </ref>
      <ref id="B20">
        <label>20</label>
        <mixed-citation>20. Bastos LAVM, Bichara JLP, Nascimento GS, Villela PB, Oliveira GMM. Mortality from Diseases of the Circulatory System in Brazil and its Relationship with Social Determinants Focusing on Vulnerability: An Ecological Study. BMC Public Health. 2022;22(1):1947. doi: 10.1186/s12889-022-14294-3.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Bastos</surname>
              <given-names>LAVM</given-names>
            </name>
            <name>
              <surname>Bichara</surname>
              <given-names>JLP</given-names>
            </name>
            <name>
              <surname>Nascimento</surname>
              <given-names>GS</given-names>
            </name>
            <name>
              <surname>Villela</surname>
              <given-names>PB</given-names>
            </name>
            <name>
              <surname>Oliveira</surname>
              <given-names>GMM</given-names>
            </name>
          </person-group>
          <article-title>Mortality from Diseases of the Circulatory System in Brazil and its Relationship with Social Determinants Focusing on Vulnerability: An Ecological Study</article-title>
          <source>BMC Public Health</source>
          <year>2022</year>
          <volume>22</volume>
          <issue>1</issue>
          <size units="pages">1947</size>
          <pub-id pub-id-type="doi">10.1186/s12889-022-14294-3</pub-id>
        </element-citation>
      </ref>
      <ref id="B21">
        <label>21</label>
        <mixed-citation>21. Brant LCC, Pinheiro PC, Passaglia LG, Souza MFM, Malta DC, Banerjee A, et al. Cardiovascular Mortality in Brazil during the COVID-19 Pandemic: A Comparison between Underlying and Multiple Causes of Death. Public Health. 2023;224:131-9. doi: 10.1016/j.puhe.2023.08.027.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Brant</surname>
              <given-names>LCC</given-names>
            </name>
            <name>
              <surname>Pinheiro</surname>
              <given-names>PC</given-names>
            </name>
            <name>
              <surname>Passaglia</surname>
              <given-names>LG</given-names>
            </name>
            <name>
              <surname>Souza</surname>
              <given-names>MFM</given-names>
            </name>
            <name>
              <surname>Malta</surname>
              <given-names>DC</given-names>
            </name>
            <name>
              <surname>Banerjee</surname>
              <given-names>A</given-names>
            </name>
            <etal>et al</etal>
          </person-group>
          <article-title>Cardiovascular Mortality in Brazil during the COVID-19 Pandemic: A Comparison between Underlying and Multiple Causes of Death</article-title>
          <source>Public Health</source>
          <year>2023</year>
          <volume>224</volume>
          <fpage>131</fpage>
          <lpage>139</lpage>
          <pub-id pub-id-type="doi">10.1016/j.puhe.2023.08.027</pub-id>
        </element-citation>
      </ref>
      <ref id="B22">
        <label>22</label>
        <mixed-citation>22. Castillo MG, Gillespie DO, Allen K, Bandosz P, Schmid V, Capewell S, et al. Future Declines of Coronary Heart Disease Mortality in England and Wales Could Counter the Burden of Population Ageing. PLoS One. 2014;9(6):e99482. doi: 10.1371/journal.pone.0099482.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Castillo</surname>
              <given-names>MG</given-names>
            </name>
            <name>
              <surname>Gillespie</surname>
              <given-names>DO</given-names>
            </name>
            <name>
              <surname>Allen</surname>
              <given-names>K</given-names>
            </name>
            <name>
              <surname>Bandosz</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Schmid</surname>
              <given-names>V</given-names>
            </name>
            <name>
              <surname>Capewell</surname>
              <given-names>S</given-names>
            </name>
            <etal>et al</etal>
          </person-group>
          <article-title>Future Declines of Coronary Heart Disease Mortality in England and Wales Could Counter the Burden of Population Ageing</article-title>
          <source>PLoS One</source>
          <year>2014</year>
          <volume>9</volume>
          <issue>6</issue>
          <elocation-id>e99482</elocation-id>
          <pub-id pub-id-type="doi">10.1371/journal.pone.0099482</pub-id>
        </element-citation>
      </ref>
      <ref id="B23">
        <label>23</label>
        <mixed-citation>23. Gunnoo T, Hasan N, Khan MS, Slark J, Bentley P, Sharma P. Quantifying the Risk of Heart Disease Following Acute Ischaemic Stroke: A Meta-Analysis of Over 50,000 Participants. BMJ Open. 2016;6(1):e009535. doi: 10.1136/bmjopen-2015-009535.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Gunnoo</surname>
              <given-names>T</given-names>
            </name>
            <name>
              <surname>Hasan</surname>
              <given-names>N</given-names>
            </name>
            <name>
              <surname>Khan</surname>
              <given-names>MS</given-names>
            </name>
            <name>
              <surname>Slark</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Bentley</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Sharma</surname>
              <given-names>P</given-names>
            </name>
          </person-group>
          <article-title>Quantifying the Risk of Heart Disease Following Acute Ischaemic Stroke: A Meta-Analysis of Over 50,000 Participants</article-title>
          <source>BMJ Open</source>
          <year>2016</year>
          <volume>6</volume>
          <issue>1</issue>
          <elocation-id>e009535</elocation-id>
          <pub-id pub-id-type="doi">10.1136/bmjopen-2015-009535</pub-id>
        </element-citation>
      </ref>
      <ref id="B24">
        <label>24</label>
        <mixed-citation>24. Gagliardi VDB, Gagliardi RJ. Current and Future Conditions of Stroke Care in Brazil. Arq Neuropsiquiatr. 2019;77(1):68-9. doi: 10.1590/0004-282X20180160.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Gagliardi</surname>
              <given-names>VDB</given-names>
            </name>
            <name>
              <surname>Gagliardi</surname>
              <given-names>RJ</given-names>
            </name>
          </person-group>
          <article-title>Current and Future Conditions of Stroke Care in Brazil</article-title>
          <source>Arq Neuropsiquiatr</source>
          <year>2019</year>
          <volume>77</volume>
          <issue>1</issue>
          <fpage>68</fpage>
          <lpage>69</lpage>
          <pub-id pub-id-type="doi">10.1590/0004-282X20180160</pub-id>
        </element-citation>
      </ref>
      <ref id="B25">
        <label>25</label>
        <mixed-citation>25. Eid MA, Mehta K, Barnes JA, Wanken Z, Columbo JA, Stone DH, et al. The Global Burden of Peripheral Artery Disease. J Vasc Surg. 2023;77(4):1119-1126.e1. doi: 10.1016/j.jvs.2022.12.015.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Eid</surname>
              <given-names>MA</given-names>
            </name>
            <name>
              <surname>Mehta</surname>
              <given-names>K</given-names>
            </name>
            <name>
              <surname>Barnes</surname>
              <given-names>JA</given-names>
            </name>
            <name>
              <surname>Wanken</surname>
              <given-names>Z</given-names>
            </name>
            <name>
              <surname>Columbo</surname>
              <given-names>JA</given-names>
            </name>
            <name>
              <surname>Stone</surname>
              <given-names>DH</given-names>
            </name>
            <etal>et al</etal>
          </person-group>
          <article-title>The Global Burden of Peripheral Artery Disease</article-title>
          <source>J Vasc Surg</source>
          <year>2023</year>
          <volume>77</volume>
          <issue>4</issue>
          <fpage>1119</fpage>
          <lpage>1126.e1</lpage>
          <pub-id pub-id-type="doi">10.1016/j.jvs.2022.12.015</pub-id>
        </element-citation>
      </ref>
      <ref id="B26">
        <label>26</label>
        <mixed-citation>26. Demsas F, Joiner MM, Telma K, Flores AM, Teklu S, Ross EG. Disparities in Peripheral Artery Disease Care: A Review and Call for Action. Semin Vasc Surg. 2022;35(2):141-54. doi: 10.1053/j.semvascsurg.2022.05.003.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Demsas</surname>
              <given-names>F</given-names>
            </name>
            <name>
              <surname>Joiner</surname>
              <given-names>MM</given-names>
            </name>
            <name>
              <surname>Telma</surname>
              <given-names>K</given-names>
            </name>
            <name>
              <surname>Flores</surname>
              <given-names>AM</given-names>
            </name>
            <name>
              <surname>Teklu</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Ross</surname>
              <given-names>EG</given-names>
            </name>
          </person-group>
          <article-title>Disparities in Peripheral Artery Disease Care: A Review and Call for Action</article-title>
          <source>Semin Vasc Surg</source>
          <year>2022</year>
          <volume>35</volume>
          <issue>2</issue>
          <fpage>141</fpage>
          <lpage>154</lpage>
          <pub-id pub-id-type="doi">10.1053/j.semvascsurg.2022.05.003</pub-id>
        </element-citation>
      </ref>
      <ref id="B27">
        <label>27</label>
        <mixed-citation>27. Nascimento BR, Brant LC, Lana ML, Lopes EL, Ribeiro AL. Trends in Procedure Type, Morbidity and in-Hospital Outcomes of Patients with Peripheral Artery Disease: Data from the Brazilian Public Health System. Ann Vasc Surg. 2016;31:143-51. doi: 10.1016/j.avsg.2015.08.019.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Nascimento</surname>
              <given-names>BR</given-names>
            </name>
            <name>
              <surname>Brant</surname>
              <given-names>LC</given-names>
            </name>
            <name>
              <surname>Lana</surname>
              <given-names>ML</given-names>
            </name>
            <name>
              <surname>Lopes</surname>
              <given-names>EL</given-names>
            </name>
            <name>
              <surname>Ribeiro</surname>
              <given-names>AL</given-names>
            </name>
          </person-group>
          <article-title>Trends in Procedure Type, Morbidity and in-Hospital Outcomes of Patients with Peripheral Artery Disease: Data from the Brazilian Public Health System</article-title>
          <source>Ann Vasc Surg</source>
          <year>2016</year>
          <volume>31</volume>
          <fpage>143</fpage>
          <lpage>151</lpage>
          <pub-id pub-id-type="doi">10.1016/j.avsg.2015.08.019</pub-id>
        </element-citation>
      </ref>
      <ref id="B28">
        <label>28</label>
        <mixed-citation>28. Juan-Salvadores P, Castro-Rodr&#237;guez M, Jim&#233;nez-D&#237;az VA, Veiga C, Busto L, Fern&#225;ndez-Barbeira S, et al. Sex Differences in Delay Times in ST-Segment Elevation Myocardial Infarction: A Cohort Study. Med Clin. 2024;163(3):115-20. doi: 10.1016/j.medcli.2024.02.015.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Juan-Salvadores</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Castro-Rodr&#237;guez</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Jim&#233;nez-D&#237;az</surname>
              <given-names>VA</given-names>
            </name>
            <name>
              <surname>Veiga</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Busto</surname>
              <given-names>L</given-names>
            </name>
            <name>
              <surname>Fern&#225;ndez-Barbeira</surname>
              <given-names>S</given-names>
            </name>
            <etal>et al</etal>
          </person-group>
          <article-title>Sex Differences in Delay Times in ST-Segment Elevation Myocardial Infarction: A Cohort Study</article-title>
          <source>Med Clin</source>
          <year>2024</year>
          <volume>163</volume>
          <issue>3</issue>
          <fpage>115</fpage>
          <lpage>120</lpage>
          <pub-id pub-id-type="doi">10.1016/j.medcli.2024.02.015</pub-id>
        </element-citation>
      </ref>
      <ref id="B29">
        <label>29</label>
        <mixed-citation>29. Wolosker N, Silva MFA, Portugal MFC, Stabellini N, Zerati AE, Szlejf C, et al. Epidemiological Analysis of Lower Limb Revascularization for Peripheral Arterial Disease Over 12 Years on the Public Healthcare System in Brazil. J Vasc Bras. 2022;21:e20210215. doi: 10.1590/1677-5449.202102152.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Wolosker</surname>
              <given-names>N</given-names>
            </name>
            <name>
              <surname>Silva</surname>
              <given-names>MFA</given-names>
            </name>
            <name>
              <surname>Portugal</surname>
              <given-names>MFC</given-names>
            </name>
            <name>
              <surname>Stabellini</surname>
              <given-names>N</given-names>
            </name>
            <name>
              <surname>Zerati</surname>
              <given-names>AE</given-names>
            </name>
            <name>
              <surname>Szlejf</surname>
              <given-names>C</given-names>
            </name>
            <etal>et al</etal>
          </person-group>
          <article-title>Epidemiological Analysis of Lower Limb Revascularization for Peripheral Arterial Disease Over 12 Years on the Public Healthcare System in Brazil</article-title>
          <source>J Vasc Bras</source>
          <year>2022</year>
          <volume>21</volume>
          <elocation-id>e20210215</elocation-id>
          <pub-id pub-id-type="doi">10.1590/1677-5449.202102152</pub-id>
        </element-citation>
      </ref>
      <ref id="B30">
        <label>30</label>
        <mixed-citation>30. Brasil. Minist&#233;rio da Sa&#250;de. Plano de A&#231;&#245;es Estrat&#233;gicas para o Enfrentamento das Doen&#231;as Cr&#244;nicas e Agravos N&#227;o Transmiss&#237;veis no Brasil, 2021-2030 (Plano de Dant) [Internet]. Bras&#237;lia: Minist&#233;rio da Sa&#250;de; 2021 [cited 2025 Sep 30]. Available from: <ext-link ext-link-type="uri" xlink:href="https://www.gov.br/saude/pt-br/centrais-de-conteudo/publicacoes/svsa/doencas-cronicas-nao-transmissiveis-dcnt/09-plano-de-dant-2022_2030.pdf/view">https://www.gov.br/saude/pt-br/centrais-de-conteudo/publicacoes/svsa/doencas-cronicas-nao-transmissiveis-dcnt/09-plano-de-dant-2022_2030.pdf/view</ext-link>.</mixed-citation>
        <element-citation publication-type="webpage">
          <person-group person-group-type="author">
            <collab>Brasil</collab>
            <collab>Minist&#233;rio da Sa&#250;de</collab>
          </person-group>
          <source>Plano de A&#231;&#245;es Estrat&#233;gicas para o Enfrentamento das Doen&#231;as Cr&#244;nicas e Agravos N&#227;o Transmiss&#237;veis no Brasil, 2021-2030 (Plano de Dant)</source>
          <comment>Internet</comment>
          <publisher-loc>Bras&#237;lia</publisher-loc>
          <publisher-name>Minist&#233;rio da Sa&#250;de</publisher-name>
          <year>2021</year>
          <date-in-citation content-type="cited-date">cited 2025 Sep 30</date-in-citation>
          <ext-link ext-link-type="uri" xlink:href="https://www.gov.br/saude/pt-br/centrais-de-conteudo/publicacoes/svsa/doencas-cronicas-nao-transmissiveis-dcnt/09-plano-de-dant-2022_2030.pdf/view">https://www.gov.br/saude/pt-br/centrais-de-conteudo/publicacoes/svsa/doencas-cronicas-nao-transmissiveis-dcnt/09-plano-de-dant-2022_2030.pdf/view</ext-link>
        </element-citation>
      </ref>
      <ref id="B31">
        <label>31</label>
        <mixed-citation>31. Brasil. C&#226;mara dos Deputados. Projeto de Lei n&#186; 5475/2023 [Internet]. Bras&#237;lia: C&#226;mara dos Deputados; 2023 [cited 2025 Sep 30]. Available from: <ext-link ext-link-type="uri" xlink:href="https://www.camara.leg.br/proposicoesWeb/prop_mostrarintegra?codteor=2364431&amp;filename=PL%205475/2023">https://www.camara.leg.br/proposicoesWeb/prop_mostrarintegra?codteor=2364431&amp;filename=PL%205475/2023</ext-link>.</mixed-citation>
        <element-citation publication-type="webpage">
          <person-group person-group-type="author">
            <collab>Brasil</collab>
            <collab>C&#226;mara dos Deputados</collab>
          </person-group>
          <source>Projeto de Lei n&#186; 5475/2023</source>
          <comment>Internet</comment>
          <publisher-loc>Bras&#237;lia</publisher-loc>
          <publisher-name>C&#226;mara dos Deputados</publisher-name>
          <year>2023</year>
          <date-in-citation content-type="cited-date">cited 2025 Sep 30</date-in-citation>
          <ext-link ext-link-type="uri" xlink:href="https://www.camara.leg.br/proposicoesWeb/prop_mostrarintegra?codteor=2364431&amp;filename=PL%205475/2023">https://www.camara.leg.br/proposicoesWeb/prop_mostrarintegra?codteor=2364431&amp;filename=PL%205475/2023</ext-link>
        </element-citation>
      </ref>
      <ref id="B32">
        <label>32</label>
        <mixed-citation>32. Silva GA, Giovanella L, Camargo KR Jr. Brazil's National Health Care System at Risk for Losing Its Universal Character. Am J Public Health. 2020;110(6):811-2. doi: 10.2105/AJPH.2020.305649.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Silva</surname>
              <given-names>GA</given-names>
            </name>
            <name>
              <surname>Giovanella</surname>
              <given-names>L</given-names>
            </name>
            <name>
              <surname>Camargo</surname>
              <given-names>KR</given-names>
              <suffix>Jr</suffix>
            </name>
          </person-group>
          <article-title>Brazil's National Health Care System at Risk for Losing Its Universal Character</article-title>
          <source>Am J Public Health</source>
          <year>2020</year>
          <volume>110</volume>
          <issue>6</issue>
          <fpage>811</fpage>
          <lpage>812</lpage>
          <pub-id pub-id-type="doi">10.2105/AJPH.2020.305649</pub-id>
        </element-citation>
      </ref>
      <ref id="B33">
        <label>33</label>
        <mixed-citation>33. Silva PGMBE, Berwanger O, Precoma DB, Cavalcante MA, Vilela-Martin JF, Figueiredo EL, et al. Evaluation of 1-Year Follow-up of Patients Included in the Registry of Clinical Practice in Patients at High Cardiovascular Risk (REACT). Arq Bras Cardiol. 2021;116(1):108-16. doi: 10.36660/abc.20190885.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Silva</surname>
              <given-names>PGMBE</given-names>
            </name>
            <name>
              <surname>Berwanger</surname>
              <given-names>O</given-names>
            </name>
            <name>
              <surname>Precoma</surname>
              <given-names>DB</given-names>
            </name>
            <name>
              <surname>Cavalcante</surname>
              <given-names>MA</given-names>
            </name>
            <name>
              <surname>Vilela-Martin</surname>
              <given-names>JF</given-names>
            </name>
            <name>
              <surname>Figueiredo</surname>
              <given-names>EL</given-names>
            </name>
            <etal>et al</etal>
          </person-group>
          <article-title>Evaluation of 1-Year Follow-up of Patients Included in the Registry of Clinical Practice in Patients at High Cardiovascular Risk (REACT)</article-title>
          <source>Arq Bras Cardiol</source>
          <year>2021</year>
          <volume>116</volume>
          <issue>1</issue>
          <fpage>108</fpage>
          <lpage>116</lpage>
          <pub-id pub-id-type="doi">10.36660/abc.20190885</pub-id>
        </element-citation>
      </ref>
      <ref id="B34">
        <label>34</label>
        <mixed-citation>34. European Society of Cardiology. ESC Atlas in General Cardiology [Internet]. Biot: ESC; 2024 [cited 2025 Sep 30]. Available from: <ext-link ext-link-type="uri" xlink:href="https://eatlas.escardio.org/Atlas/ESC-Atlas-of-Cardiology/Cardiovascular-healthcare-delivery/Cardiological-specialists/chr_card_1m_r-cardiologists-total-per-million-people">https://eatlas.escardio.org/Atlas/ESC-Atlas-of-Cardiology/Cardiovascular-healthcare-delivery/Cardiological-specialists/chr_card_1m_r-cardiologists-total-per-million-people</ext-link>.</mixed-citation>
        <element-citation publication-type="webpage">
          <person-group person-group-type="author">
            <collab>European Society of Cardiology</collab>
          </person-group>
          <source>ESC Atlas in General Cardiology</source>
          <comment>Internet</comment>
          <publisher-loc>Biot</publisher-loc>
          <publisher-name>ESC</publisher-name>
          <year>2024</year>
          <date-in-citation content-type="cited-date">cited 2025 Sep 30</date-in-citation>
          <comment>
            <ext-link ext-link-type="uri" xlink:href="https://eatlas.escardio.org/Atlas/ESC-Atlas-of-Cardiology/Cardiovascular-healthcare-delivery/Cardiological-specialists/chr_card_1m_r-cardiologists-total-per-million-people">https://eatlas.escardio.org/Atlas/ESC-Atlas-of-Cardiology/Cardiovascular-healthcare-delivery/Cardiological-specialists/chr_card_1m_r-cardiologists-total-per-million-people</ext-link>
          </comment>
        </element-citation>
      </ref>
      <ref id="B35">
        <label>35</label>
        <mixed-citation>35. Nawsherwan, Khan SA, Mubarik S, Le Z, Akbar F, Wang Y. Epidemiological Trends and Age-Period-Cohort Effects on Cardiovascular Diseases Burden Attributable to Ambient Air Pollution Across BRICS. Sci Rep. 2024;14(1):11464. doi: 10.1038/s41598-024-62295-6.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Nawsherwan</surname>
              <given-names>Khan SA</given-names>
            </name>
            <name>
              <surname>Mubarik</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Le</surname>
              <given-names>Z</given-names>
            </name>
            <name>
              <surname>Akbar</surname>
              <given-names>F</given-names>
            </name>
            <name>
              <surname>Wang</surname>
              <given-names>Y</given-names>
            </name>
          </person-group>
          <article-title>Epidemiological Trends and Age-Period-Cohort Effects on Cardiovascular Diseases Burden Attributable to Ambient Air Pollution Across BRICS</article-title>
          <source>Sci Rep</source>
          <year>2024</year>
          <volume>14</volume>
          <issue>1</issue>
          <size units="pages">11464</size>
          <pub-id pub-id-type="doi">10.1038/s41598-024-62295-6</pub-id>
        </element-citation>
      </ref>
      <ref id="B36">
        <label>36</label>
        <mixed-citation>36. Brant LCC, Nascimento BR, Veloso GA, Gomes CS, Polanczyk C, Oliveira GMM, et al. Burden of Cardiovascular Diseases Attributable to Risk Factors in Brazil: Data from the "Global Burden of Disease 2019" Study. Rev Soc Bras Med Trop. 2022;55(suppl 1):e0263. doi: 10.1590/0037-8682-0263-2021.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Brant</surname>
              <given-names>LCC</given-names>
            </name>
            <name>
              <surname>Nascimento</surname>
              <given-names>BR</given-names>
            </name>
            <name>
              <surname>Veloso</surname>
              <given-names>GA</given-names>
            </name>
            <name>
              <surname>Gomes</surname>
              <given-names>CS</given-names>
            </name>
            <name>
              <surname>Polanczyk</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Oliveira</surname>
              <given-names>GMM</given-names>
            </name>
            <etal>et al</etal>
          </person-group>
          <article-title>Burden of Cardiovascular Diseases Attributable to Risk Factors in Brazil: Data from the "Global Burden of Disease 2019" Study</article-title>
          <source>Rev Soc Bras Med Trop</source>
          <year>2022</year>
          <volume>55</volume>
          <supplement>suppl 1</supplement>
          <elocation-id>e0263</elocation-id>
          <pub-id pub-id-type="doi">10.1590/0037-8682-0263-2021</pub-id>
        </element-citation>
      </ref>
      <ref id="B37">
        <label>37</label>
        <mixed-citation>37. Malta DC, Felisbino-Mendes MS, Machado &#205;E, Veloso GA, Gomes CS, Brant LCC, et al. Burden of Disease Attributable to Risk Factors in Brazil: An Analysis of National and Subnational Estimates from the 2019 Global Burden of Disease Study. Rev Soc Bras Med Trop. 2022;55(suppl 1):e0262. doi: 10.1590/0037-8682-0262-2021.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Malta</surname>
              <given-names>DC</given-names>
            </name>
            <name>
              <surname>Felisbino-Mendes</surname>
              <given-names>MS</given-names>
            </name>
            <name>
              <surname>Machado</surname>
              <given-names>&#205;E</given-names>
            </name>
            <name>
              <surname>Veloso</surname>
              <given-names>GA</given-names>
            </name>
            <name>
              <surname>Gomes</surname>
              <given-names>CS</given-names>
            </name>
            <name>
              <surname>Brant</surname>
              <given-names>LCC</given-names>
            </name>
            <etal>et al</etal>
          </person-group>
          <article-title>Burden of Disease Attributable to Risk Factors in Brazil: An Analysis of National and Subnational Estimates from the 2019 Global Burden of Disease Study</article-title>
          <source>Rev Soc Bras Med Trop</source>
          <year>2022</year>
          <volume>55</volume>
          <supplement>suppl 1</supplement>
          <elocation-id>e0262</elocation-id>
          <pub-id pub-id-type="doi">10.1590/0037-8682-0262-2021</pub-id>
        </element-citation>
      </ref>
      <ref id="B38">
        <label>38</label>
        <mixed-citation>38. Nascimento BR, Brant LCC, Yadgir S, Oliveira GMM, Roth G, Glenn SD, et al. Trends in Prevalence, Mortality, and Morbidity Associated with High Systolic Blood Pressure in Brazil from 1990 to 2017: Estimates from the "Global Burden of Disease 2017" (GBD 2017) Study. Popul Health Metr. 2020;18(Suppl 1):17. doi: 10.1186/s12963-020-00218-z.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Nascimento</surname>
              <given-names>BR</given-names>
            </name>
            <name>
              <surname>Brant</surname>
              <given-names>LCC</given-names>
            </name>
            <name>
              <surname>Yadgir</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Oliveira</surname>
              <given-names>GMM</given-names>
            </name>
            <name>
              <surname>Roth</surname>
              <given-names>G</given-names>
            </name>
            <name>
              <surname>Glenn</surname>
              <given-names>SD</given-names>
            </name>
            <etal>et al</etal>
          </person-group>
          <article-title>Trends in Prevalence, Mortality, and Morbidity Associated with High Systolic Blood Pressure in Brazil from 1990 to 2017: Estimates from the "Global Burden of Disease 2017" (GBD 2017) Study</article-title>
          <source>Popul Health Metr</source>
          <year>2020</year>
          <volume>18</volume>
          <supplement>Suppl 1</supplement>
          <size units="pages">17</size>
          <pub-id pub-id-type="doi">10.1186/s12963-020-00218-z</pub-id>
        </element-citation>
      </ref>
      <ref id="B39">
        <label>39</label>
        <mixed-citation>39. Zavascki AP. Brazil's Family Health Strategy. N Engl J Med. 2015;373(13):1277-8. doi: 10.1056/NEJMc1509056.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Zavascki</surname>
              <given-names>AP</given-names>
            </name>
          </person-group>
          <article-title>Brazil's Family Health Strategy</article-title>
          <source>N Engl J Med</source>
          <year>2015</year>
          <volume>373</volume>
          <issue>13</issue>
          <fpage>1277</fpage>
          <lpage>1278</lpage>
          <pub-id pub-id-type="doi">10.1056/NEJMc1509056</pub-id>
        </element-citation>
      </ref>
      <ref id="B40">
        <label>40</label>
        <mixed-citation>40. Malta DC, Teixeira R, Oliveira GMM, Ribeiro ALP. Cardiovascular Disease Mortality According to the Brazilian Information System on Mortality and the Global Burden of Disease Study Estimates in Brazil, 2000-2017. Arq Bras Cardiol. 2020;115(2):152-60. doi: 10.36660/abc.20190867.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Malta</surname>
              <given-names>DC</given-names>
            </name>
            <name>
              <surname>Teixeira</surname>
              <given-names>R</given-names>
            </name>
            <name>
              <surname>Oliveira</surname>
              <given-names>GMM</given-names>
            </name>
            <name>
              <surname>Ribeiro</surname>
              <given-names>ALP</given-names>
            </name>
          </person-group>
          <article-title>Cardiovascular Disease Mortality According to the Brazilian Information System on Mortality and the Global Burden of Disease Study Estimates in Brazil, 2000-2017</article-title>
          <source>Arq Bras Cardiol</source>
          <year>2020</year>
          <volume>115</volume>
          <issue>2</issue>
          <fpage>152</fpage>
          <lpage>160</lpage>
          <pub-id pub-id-type="doi">10.36660/abc.20190867</pub-id>
        </element-citation>
      </ref>
      <ref id="B41">
        <label>41</label>
        <mixed-citation>41. Baptista EA, Queiroz BL, Rigotti JIR. Decomposition of Mortality Rates from Cardiovascular Disease in the Adult Population: A Study for Brazilian Micro-Regions between 1996 and 2015. Rev Bras Estud Popul. 2018;35(2):e0050. doi: 10.20947/S102-3098a005.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Baptista</surname>
              <given-names>EA</given-names>
            </name>
            <name>
              <surname>Queiroz</surname>
              <given-names>BL</given-names>
            </name>
            <name>
              <surname>Rigotti</surname>
              <given-names>JIR</given-names>
            </name>
          </person-group>
          <article-title>Decomposition of Mortality Rates from Cardiovascular Disease in the Adult Population: A Study for Brazilian Micro-Regions between 1996 and 2015</article-title>
          <source>Rev Bras Estud Popul</source>
          <year>2018</year>
          <volume>35</volume>
          <issue>2</issue>
          <elocation-id>e0050</elocation-id>
          <pub-id pub-id-type="doi">10.20947/S102-3098a005</pub-id>
        </element-citation>
      </ref>
    </ref-list>
    <fn-group>
      <fn fn-type="other">
        <label>Vincula&#231;&#227;o acad&#234;mica:</label>
        <p> N&#227;o h&#225; vincula&#231;&#227;o deste estudo a programas de p&#243;s-gradua&#231;&#227;o.</p>
      </fn>
      <fn fn-type="other">
        <label>Aprova&#231;&#227;o &#233;tica e consentimento informado:</label>
        <p> Este artigo n&#227;o cont&#233;m estudos com humanos ou animais realizados por nenhum dos autores.</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">
        <label>Disponibilidade de Dados:</label>
        <p> Os conte&#250;dos est&#227;o dispon&#237;veis no portal do GBD 2021 que pode ser acessado em: <ext-link ext-link-type="uri" xlink:href="https://vizhub.healthdata.org/gbd-results/">https://vizhub.healthdata.org/gbd-results/</ext-link>. Pesquisadores podem se registrar e baixar os dados gratuitamente por meio dessa plataforma. Todos os dados utilizados neste estudo &#8212; incluindo contagens de mortalidade e estimativas populacionais de meio de ano &#8212;, bem como os scripts em R usados na an&#225;lise, foram depositados em um reposit&#243;rio p&#250;blico no GitHub: <ext-link ext-link-type="uri" xlink:href="https://github.com/svd09/Brazil_CVD">https://github.com/svd09/Brazil_CVD</ext-link>. Alternativamente, leitores interessados podem solicitar um arquivo compactado com todo o material entrando em contato com o autor correspondente.</p>
      </fn>
      <fn fn-type="financial-disclosure">
        <label>Fontes de financiamento:</label>
        <p> O presente estudo n&#227;o teve fontes de financiamento externas.</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.20250189i</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Original Article</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Forecasting Ischemic Heart Disease, Stroke, and Peripheral Artery Disease Mortality in Brazil Through 2040: A Bayesian Modeling Approach</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-5116-5062</contrib-id>
          <name>
            <surname>Salerno</surname>
            <given-names>Pedro Rafael Vieira de Oliveira</given-names>
          </name>
          <role>Conception and design of the research</role>
          <role>Acquisition of data</role>
          <role>Analysis and interpretation of the data</role>
          <role>Statistical analysis</role>
          <role>Writing of the manuscript</role>
          <role>Critical revision of the manuscript for content</role>
          <xref ref-type="aff" rid="aff1001">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Cotton</surname>
            <given-names>Antoinette</given-names>
          </name>
          <role>Conception and design of the research</role>
          <role>Statistical analysis</role>
          <role>Writing of the manuscript</role>
          <role>Critical revision of the manuscript for content</role>
          <xref ref-type="aff" rid="aff3001">
            <sup>3</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Nascimento</surname>
            <given-names>Bruno R.</given-names>
          </name>
          <role>Conception and design of the research</role>
          <role>Critical revision of the manuscript for content</role>
          <xref ref-type="aff" rid="aff4001">
            <sup>4</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Chen</surname>
            <given-names>Zhuo</given-names>
          </name>
          <role>Acquisition of data</role>
          <role>Statistical analysis</role>
          <role>Critical revision of the manuscript for content</role>
          <xref ref-type="aff" rid="aff2001">
            <sup>2</sup>
          </xref>
          <xref ref-type="aff" rid="aff3001">
            <sup>3</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Pereira</surname>
            <given-names>Gabriel Tensol Rodrigues</given-names>
          </name>
          <role>Critical revision of the manuscript for content</role>
          <xref ref-type="aff" rid="aff3001">
            <sup>3</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Abizaid</surname>
            <given-names>Alexandre A.</given-names>
          </name>
          <role>Critical revision of the manuscript for content</role>
          <xref ref-type="aff" rid="aff5001">
            <sup>5</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-8122-6647</contrib-id>
          <name>
            <surname>Dallan</surname>
            <given-names>Luis Augusto Palma</given-names>
          </name>
          <role>Critical revision of the manuscript for content</role>
          <xref ref-type="aff" rid="aff2001">
            <sup>2</sup>
          </xref>
          <xref ref-type="aff" rid="aff6001">
            <sup>6</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0009-0007-4241-0656</contrib-id>
          <name>
            <surname>Salerno</surname>
            <given-names>Pedro Rafael</given-names>
          </name>
          <role>Critical revision of the manuscript for content</role>
          <xref ref-type="aff" rid="aff7001">
            <sup>7</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Al-Kindi</surname>
            <given-names>Sadeer</given-names>
          </name>
          <role>Critical revision of the manuscript for content</role>
          <xref ref-type="aff" rid="aff8001">
            <sup>8</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Petermann-Rocha</surname>
            <given-names>Fanny</given-names>
          </name>
          <role>Conception and design of the research</role>
          <role>Critical revision of the manuscript for content</role>
          <xref ref-type="aff" rid="aff9001">
            <sup>9</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Deo</surname>
            <given-names>Salil V.</given-names>
          </name>
          <role>Conception and design of the research</role>
          <role>Analysis and interpretation of the data</role>
          <role>Statistical analysis</role>
          <role>Writing of the manuscript</role>
          <role>Critical revision of the manuscript for content</role>
          <xref ref-type="aff" rid="aff3001">
            <sup>3</sup>
          </xref>
          <xref ref-type="aff" rid="aff10001">
            <sup>10</sup>
          </xref>
          <xref ref-type="aff" rid="aff11001">
            <sup>11</sup>
          </xref>
        </contrib>
      </contrib-group>
      <aff id="aff1001">
        <label>1</label>
        <country country="US">USA</country>
        <institution content-type="original">Department of Medicine, NYC Health + Hospitals/Elmhurst, Icahn School of Medicine at Mt. Sinai, Queens, NY &#8211; USA</institution>
      </aff>
      <aff id="aff2001">
        <label>2</label>
        <country country="US">USA</country>
        <institution content-type="original">University Hospitals of Cleveland, Cleveland, Ohio &#8211; USA</institution>
      </aff>
      <aff id="aff3001">
        <label>3</label>
        <country country="US">USA</country>
        <institution content-type="original">Case Western Reserve University, Cleveland &#8211; USA</institution>
      </aff>
      <aff id="aff4001">
        <label>4</label>
        <country country="BR">Brazil</country>
        <institution content-type="original">Universidade Federal de Minas Gerais, Belo Horizonte, MG &#8211; Brazil</institution>
      </aff>
      <aff id="aff5001">
        <label>5</label>
        <country country="BR">Brazil</country>
        <institution content-type="original">Hospital Israelita Albert Einstein, S&#227;o Paulo, SP &#8211; Brazil</institution>
      </aff>
      <aff id="aff6001">
        <label>6</label>
        <country country="BR">Brazil</country>
        <institution content-type="original">Instituto do Cora&#231;&#227;o do Hospital das Cl&#237;nicas da Faculdade de Medicina da Universidade de S&#227;o Paulo, S&#227;o Paulo, SP &#8211; Brazil</institution>
      </aff>
      <aff id="aff7001">
        <label>7</label>
        <country country="BR">Brazil</country>
        <institution content-type="original">Universidade Cat&#243;lica de Pernambuco, Recife, PE &#8211; Brazil</institution>
      </aff>
      <aff id="aff8001">
        <label>8</label>
        <country country="US">USA</country>
        <institution content-type="original">Center for Health and Nature Houston Methodist, Houston &#8211; USA</institution>
      </aff>
      <aff id="aff9001">
        <label>9</label>
        <country country="CL">Chile</country>
        <institution content-type="original">Universidad Diego Portales, Santiago &#8211; Chile</institution>
      </aff>
      <aff id="aff10001">
        <label>10</label>
        <country country="US">USA</country>
        <institution content-type="original">Louis Stokes VA Medical Center, Cleveland, Ohio &#8211; USA</institution>
      </aff>
      <aff id="aff11001">
        <label>11</label>
        <country country="GB">England</country>
        <institution content-type="original">University of Glasgow, Glasgow &#8211; England</institution>
      </aff>
      <author-notes>
        <corresp id="c01001"><label>Mailing Address:</label> Salil V. Deo Case Western Reserve University School of Medicine Health Education Campus - 9501 Euclid Ave, Cleveland, OH 44106. Email: svd14@case.edu </corresp>
        <fn fn-type="edited-by">
          <label>Editor responsible for the review:</label>
          <p>Marcio Bittencourt</p>
        </fn>
        <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>
      </author-notes>
      <abstract>
        <title>Abstract</title>
        <sec>
          <title>Background</title>
          <p> Atherosclerotic cardiovascular disease &#8212; particularly ischemic heart disease (IHD), stroke, and peripheral artery disease (PAD) &#8212; is the leading cause of cardiovascular mortality in Brazil.</p>
        </sec>
        <sec>
          <title>Objectives</title>
          <p> This study aimed to project mortality trends for IHD, stroke, and PAD in Brazil through 2040.</p>
        </sec>
        <sec>
          <title>Methods</title>
          <p> Annual death counts (1990-2021) for IHD, stroke, and PAD among individuals aged 40-79 years were obtained from the Global Burden of Disease (GBD) 2021 study. Mid-year population estimates for both observed (1990-2021) and projected (2022-2040) periods were used. Crude and age-standardized mortality rates were calculated. Bayesian age-period-cohort models were applied to project mortality rates from 2022 to 2040. Relative percentage changes and estimated annual percentage changes (EAPCs) were computed. Projections (per 100,000 population) are reported as medians with 95% uncertainty intervals (UIs), and EAPCs include bootstrap-derived confidence intervals (CIs).</p>
        </sec>
        <sec>
          <title>Results</title>
          <p> Between 1990 and 2040, Brazil&#8217;s population aged 40-79 years is projected to grow by 237.82%. The age-standardized mortality rate for IHD is expected to decline by 14.16% [from 118.61 in 2021 to 101.82 in 2040 (95% UI, 0.36-203.27)] (EAPC: -0.83% [95% CI, -0.84 to -0.83]); and for stroke by 17.36% [from 84.58 to 69.90 (95% UI, 0-152.48)] (EAPC: -1.07% [95% CI, -1.10 to -1.04]). In contrast, PAD mortality is projected to increase by 10.99% [from 1.82 to 2.02 (95% UI, 0-5.03)] (EAPC: 0.45% [95% CI, 0.30-0.59]). Additionally, sex-specific age-standardized mortality rates showed considerable variation. For IHD, rates are projected to decline by 25.31% among men (EAPC: -1.56% [95% CI, -1.57 to -1.55]), while increasing by 4.12% among women (EAPC: 0.14% [95% CI, 0.13-0.16]). Stroke mortality is expected to decrease by 30.00% in men (EAPC: -1.94% [95% CI, -1.96 to -1.91]) and by 4.52% in women (EAPC: -0.33% [95% CI, -0.37 to -0.29]). In contrast, PAD mortality is projected to rise by 14.64% in men (EAPC: 0.55% [95% CI, 0.38 to 0.71]) and by 21.92% in women (EAPC: 0.91% [95% CI, 0.78-1.02]).</p>
        </sec>
        <sec>
          <title>Conclusion</title>
          <p> While mortality rates for IHD and stroke are projected to decline, PAD mortality is expected to rise &#8212; particularly among women &#8212; highlighting the urgent need for sex-specific and disease-specific public health interventions.</p>
        </sec>
      </abstract>
      <abstract abstract-type="graphical">
        <p>
          <fig id="f01001">
            <label>Central Illustration:</label>
            <caption>
              <title>Forecasting Ischemic Heart Disease, Stroke, and Peripheral Artery Disease Mortality in Brazil Through 2040: A Bayesian Modeling Approach</title>
            </caption>
            <attrib>Projected age-standardized mortality rates (per 100,000 population) for stroke, IHD, and PAD in Brazil. Projections were derived using Bayesian modeling based on observed mortality data from 1990 to 2021 and mid-year population estimates for 2022 to 2040. Values for both 2021 and 2040 are shown, along with their corresponding 95% UIs. The results indicate projected reductions in stroke and IHD mortality rates by 17.36% and 14.16%, respectively, whereas PAD mortality is expected to increase by 10.99%. The specific mortality rates for 2021 and 2040 are displayed below each condition. BAPC: Bayesian age-period-cohort; GBD: Global Burden of Disease; IHD: ischemic heart disease; PAD: peripheral artery disease; UI: uncertainty interval.</attrib>
            <graphic xlink:href="1678-4170-abc-122-11-e20250189-50189-gf01-en.tif"/></fig>
        </p>
      </abstract>
      <kwd-group xml:lang="en">
        <title>Keywords</title>
        <kwd>Myocardial Ischemia</kwd>
        <kwd>Stroke</kwd>
        <kwd>Peripheral Arterial Disease</kwd>
        <kwd>Mortality</kwd>
        <kwd>Brazil</kwd>
      </kwd-group>
      <funding-group>
        <funding-statement><bold>Sources of funding:</bold>There were no external funding sources for this study.</funding-statement>
      </funding-group>
    </front-stub>
    <body>
      <sec sec-type="intro">
        <title>Introduction</title>
        <p>Atherosclerotic cardiovascular disease (CVD) encompasses 3 major conditions: ischemic heart disease (IHD), stroke, and peripheral artery disease (PAD). In 2013, IHD and stroke together accounted for 247.9 deaths per 100,000 population worldwide.<sup><xref ref-type="bibr" rid="B1">1</xref></sup> For many years, both have consistently ranked among the leading causes of cardiovascular mortality across most nations. In 2019, the Global Burden of Disease (GBD) study reported that 113 million adults globally were affected by PAD, with 42% of related deaths occurring in low- and middle-income countries, including Brazil.<sup><xref ref-type="bibr" rid="B2">2</xref></sup> According to the Cardiovascular Statistics &#8211; Brazil 2023, CVD remains the leading cause of death in the country.<sup><xref ref-type="bibr" rid="B3">3</xref></sup></p>
        <p>Although the age-standardized mortality rate from CVD has declined over the past decades in Brazil, the prevalence of these conditions has increased by 26%.<sup><xref ref-type="bibr" rid="B4">4</xref>,<xref ref-type="bibr" rid="B5">5</xref></sup> Rates of obesity and dyslipidemia remain high, and according to the 2024 report by the World Health Organization (WHO), Brazil is among the top-ranking countries in tobacco use. Moreover, mortality attributable to diabetes in the country is projected to rise by 144% over the next 2 decades.<sup><xref ref-type="bibr" rid="B4">4</xref>,<xref ref-type="bibr" rid="B6">6</xref></sup></p>
        <p>Recognizing the detrimental impact of cardiovascular conditions on national health, the Brazilian Congress enacted Law No. 8,080 in 1990, establishing the Brazilian Unified Health System (SUS), a free and universal public health care system. Currently, the SUS serves more than 70% of the Brazilian population.<sup><xref ref-type="bibr" rid="B7">7</xref></sup> In addition, the Ministry of Health introduced the Family Health Program in the mid-1990s, followed by primary prevention strategies in 2002 and the implementation of a generic drug coverage policy for the treatment of hypertension, diabetes, and dyslipidemia.<sup><xref ref-type="bibr" rid="B8">8</xref></sup> These initiatives have contributed to improvements in population health. However, as public policies evolve and therapeutic options advance, the attributable burden of CVD and its components may shift. Therefore, understanding the future trajectory of these conditions is critical to guiding national health strategies.</p>
        <p>Some countries, such as the United States, Japan, and the United Kingdom, have already undertaken projections of future cardiovascular health.<sup><xref ref-type="bibr" rid="B9">9</xref>,<xref ref-type="bibr" rid="B10">10</xref></sup> In the U.S. and Japan, IHD mortality is expected to decline, while stroke-related mortality is projected to remain relatively stable. However, such findings cannot be generalized to other contexts due to variations in population structure, fertility rates, aging patterns, and migration flows. Since Brazil is among the most populous countries globally, its contribution to global estimates is substantial.</p>
        <p>Therefore, the present study aimed to project mortality rates for IHD, stroke, and PAD among Brazilian adults aged 40-79 years through 2040, based on observed data from 1990 to 2021.</p>
      </sec>
      <sec sec-type="methods">
        <title>Methods</title>
        <sec>
          <title>Data source</title>
          <sec>
            <title>IHD, stroke, and PAD mortality</title>
            <p>The primary data source for this study was the GBD 2021 study.<sup><xref ref-type="bibr" rid="B11">11</xref></sup> The GBD, a global consortium of over 12,000 collaborators, provides harmonized data on disability and mortality attributable to various health conditions and risk factors across 204 countries and territories.<sup><xref ref-type="bibr" rid="B12">12</xref></sup> The 2021 update offers public access through the Global Health Data Exchange (GHDx) query tool (http://ghdx.healthdata.org/gbd-results-tool).<sup><xref ref-type="bibr" rid="B11">11</xref></sup> As a signatory of the WHO Guidelines for Accurate and Transparent Health Estimates Reporting, GBD applies standardized data processing to ensure comparability across countries.<sup><xref ref-type="bibr" rid="B12">12</xref></sup></p>
            <p>By using GHDx, we extracted annual death counts attributed to IHD, stroke, and PAD in Brazil across 5-year age intervals (40-44, 45-49, 50-54, 55-59, 60-64, 65-69, 70-74, and 75-79 years) from 1990 to 2021. The GBD 2021 defines IHD as a composite of acute myocardial infarction, chronic stable angina, coronary artery disease, and ischemic cardiomyopathy, and PAD as an ankle-brachial index &lt; 0.9.<sup><xref ref-type="bibr" rid="B13">13</xref></sup> According to the GBD, the original source of mortality data was the Mortality Information System (SIM), a curated and quality-assessed national death certificate database managed by the Brazilian Ministry of Health.<sup><xref ref-type="bibr" rid="B14">14</xref></sup> Raw data were processed using the Cause of Death Ensemble model (CODEm), a Bayesian geospatial regression framework developed by the Institute for Health Metrics and Evaluation (Seattle, WA).<sup><xref ref-type="bibr" rid="B13">13</xref></sup> Additional details on the GBD 2021 data specific to our study are provided in the supplemental material.</p>
          </sec>
          <sec>
            <title>Population estimates</title>
            <p>We also obtained mid-year population estimates for the same age intervals (40-44 to 75-79 years) for the period 1990 to 2040 from the GBD 2021.<sup><xref ref-type="bibr" rid="B15">15</xref>,<xref ref-type="bibr" rid="B16">16</xref></sup> The original source of this estimates was the Brazilian Institute of Geography and Statistics, which conducts national censuses in Brazil.<sup><xref ref-type="bibr" rid="B15">15</xref></sup> Data were extracted for the overall population, as well as disaggregated by sex.</p>
          </sec>
        </sec>
      </sec>
      <sec>
        <title>Statistical analysis</title>
        <p>We first calculated observed annual crude and age-standardized mortality rates (per 100,000 population) for IHD, stroke, and PAD from 1990 to 2021. Age-standardized rates and corresponding 95% confidence intervals (CIs) were computed using the 1990 mid-year population as the standard, with CIs estimated via the delta method.</p>
        <p>We then applied Bayesian age-period-cohort (APC) models to the observed data (1990-2021) to project mortality rates for IHD, stroke, and PAD through 2040. APC models allow for simultaneous modeling of age, period, and cohort effects using a single regression equation and can accommodate non-linear relationships.<sup><xref ref-type="bibr" rid="B17">17</xref></sup> We used random walk 2 priors with a log-gamma distribution, and modeled the outcome variable (mortality events) using a generalized linear regression framework with a log-link and a Poisson distribution.</p>
        <p>Although multiple APC model formulations exist, recent simulation studies have shown that Bayesian APC models offer superior forecasting accuracy.<sup><xref ref-type="bibr" rid="B18">18</xref></sup> Estimates from the fitted models were obtained using the integrated nested Laplace approximation, a computationally efficient approach known to produce stable and reliable posterior estimates without convergence issues, comparable to those derived from Markov Chain Monte Carlo simulations.<sup><xref ref-type="bibr" rid="B19">19</xref></sup> Detailed information on prior specifications, projection methodology, and model assessment procedures is provided in the <xref ref-type="supplementary-material" rid="suppl01-en">supplemental material</xref>.</p>
        <p>Models were fitted for the total Brazilian population and separately for men and women. For each group, mortality rates were projected for all defined 5-year age intervals, and age-standardized rates were again indexed to the 1990 mid-year population. Projected rates are reported as medians with 95% uncertainty intervals (UIs). We also calculated the relative percentage change and the estimated annual percentage change (EAPC) between the final observed year (2021) and the final projected year (2040). EAPCs were computed using generalized linear regression with a log-link function, and 95% CIs were derived using bootstrap resampling.</p>
        <p>All analyses were conducted in R version 4.3.0 (R Foundation for Statistical Computing, Vienna, Austria). As the study relied solely on publicly available, population-level data, it was exempt from Human Research Ethics Committee approval and did not require informed consent. This study was conducted and reported in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology guidelines.</p>
        <sec>
          <title>Patient and public involvement</title>
          <p>Patients and members of the public were not involved in the design, conduct, reporting, or dissemination plans of this research, as such involvement was not deemed appropriate or feasible.</p>
        </sec>
      </sec>
      <sec sec-type="results">
        <title>Results</title>
        <p>In 1990, Brazil had 32,751,825 residents aged 40-79 years, of whom 51.7% were women. Between 1990 and 2040, this age group is projected to grow by 237.8%, accompanied by substantial population aging (Figure S1). The proportion of adults aged 75-79 years is expected to nearly double, while the share of younger age groups (e.g., 40-44 years) will decline.</p>
        <p>The age-standardized IHD mortality rate declined substantially from 1990 to 2021 (Table S1, Figure S2), and this trend is projected to continue through 2040 (<xref ref-type="table" rid="t1001">Table 1</xref>, <xref ref-type="fig" rid="f02001">Figure 1</xref>). Although reductions are expected across all age brackets, the greatest decrease is anticipated in individuals aged 60-64 years (<xref ref-type="table" rid="t1001">Table 1</xref>, Figure S3, <xref ref-type="fig" rid="f03001">Figure 2</xref>).</p>
        <p>
          <table-wrap id="t1001">
            <label>Table 1</label>
            <caption>
              <title>&#8211; Projected mortality rates (per 100,000 population) for IHD, stroke, and PAD in Brazil, by 5-year age groups (40-79 years), for 2021 (observed), 2030, and 2040 (projected)</title>
            </caption>
            <table frame="hsides" rules="groups">
              <colgroup>
                <col/>
                <col/>
                <col/>
                <col/>
                <col/>
                <col/>
                <col/>
                <col/>
                <col/>
                <col/>
                <col/>
                <col/>
              </colgroup>
              <thead>
                <tr>
                  <th align="left" style="font-weight:normal"> </th>
                  <th align="left" style="font-weight:normal"> </th>
                  <th rowspan="2">Year</th>
                  <th rowspan="2">Age- standardized rate</th>
                  <th colspan="8">Age groups (years)</th>
                </tr>
                <tr>
                  <th align="left" style="font-weight:normal"> </th>
                  <th align="left" style="font-weight:normal"> </th>
                  <th>40-44</th>
                  <th>45-49</th>
                  <th>50-54</th>
                  <th>55-59</th>
                  <th>60-64</th>
                  <th>65-69</th>
                  <th>70-74</th>
                  <th>75-79</th>
                </tr>
              </thead>
              <tbody>
                <tr>
                  <td rowspan="4">
                    <bold>IHD</bold>
                  </td>
                  <td>Observed data</td>
                  <td align="center">2021</td>
                  <td align="center">118.61 (117.90-119.32)</td>
                  <td align="center">21.37 (20.68-22.09)</td>
                  <td align="center">40.30 (39.27-41.36)</td>
                  <td align="center">70.76 (69.33-72.23)</td>
                  <td align="center">112.61 (110.70-114.54)</td>
                  <td align="center">173.32 (170.74-175.94)</td>
                  <td align="center">249.85 (246.35-253.40)</td>
                  <td align="center">354.19 (349.37-359.08)</td>
                  <td align="center">516.39 (509.22-523.65)</td>
                </tr>
                <tr>
                  <td rowspan="2">Projected results</td>
                  <td align="center">2030</td>
                  <td align="center">110.76 (72.36-149.16)</td>
                  <td align="center">19.88 (13.48-29.54)</td>
                  <td align="center">37.16 (25.90-53.67)</td>
                  <td align="center">62.84 (44.09-90.21)</td>
                  <td align="center">99.91 (70.11-143.41)</td>
                  <td align="center">155.50 (109.13-223.17)</td>
                  <td align="center">232.25 (162.99-333.31)</td>
                  <td align="center">347.29 (243.72-498.40)</td>
                  <td align="center">506.23 (355.24-726.46)</td>
                </tr>
                <tr>
                  <td align="center">2040</td>
                  <td align="center">101.82 (0.36-203.27)</td>
                  <td align="center">19.04 (6.38-57.74)</td>
                  <td align="center">35.59 (12.40-103.55)</td>
                  <td align="center">60.20 (21.46-171.18)</td>
                  <td align="center">93.99 (33.83-264.76)</td>
                  <td align="center">141.99 (51.21-399.30)</td>
                  <td align="center">210.94 (76.06-593.26)</td>
                  <td align="center">309.77 (111.71-871.19)</td>
                  <td align="center">453.55 (163.55-1275.56)</td>
                </tr>
                <tr>
                  <td>Relative percent change</td>
                  <td> </td>
                  <td align="center">-14.16%</td>
                  <td align="center">-10.90%</td>
                  <td align="center">-11.69%</td>
                  <td align="center">-14.92%</td>
                  <td align="center">-16.53%</td>
                  <td align="center">-18.08%</td>
                  <td align="center">-15.58%</td>
                  <td align="center">-12.54%</td>
                  <td align="center">-12.17%</td>
                </tr>
                <tr>
                  <td> </td>
                  <td>EAPC</td>
                  <td> </td>
                  <td align="center">-0.83 (-0.84a-0.83)</td>
                  <td align="center">-1.58 (-1.73a-1.43)</td>
                  <td align="center">-1.63 (-1.76a-1.5)</td>
                  <td align="center">-1.66 (-1.78a-1.54)</td>
                  <td align="center">-1.69 (-1.79a-1.58)</td>
                  <td align="center">-1.7 (-1.79a-1.6)</td>
                  <td align="center">-1.68 (-1.77a-1.59)</td>
                  <td align="center">-1.69 (-1.81a-1.59)</td>
                  <td align="center">-1.72 (-1.86a-1.6)</td>
                </tr>
                <tr>
                  <td rowspan="4">
                    <bold>Stroke</bold>
                  </td>
                  <td>Observed data</td>
                  <td align="center">2021</td>
                  <td align="center">84.58 (83.99-85.18)</td>
                  <td align="center">15.24 (14.66-15.85)</td>
                  <td align="center">27.11 (26.27-27.98)</td>
                  <td align="center">44.48 (43.35-45.65)</td>
                  <td align="center">67.22 (65.75-68.72)</td>
                  <td align="center">106.10 (104.09-108.16)</td>
                  <td align="center">170.44 (167.56-173.38)</td>
                  <td align="center">280.48 (276.18-284.83)</td>
                  <td align="center">467.18 (460.37-474.10)</td>
                </tr>
                <tr>
                  <td rowspan="2">Projected results</td>
                  <td align="center">2030</td>
                  <td align="center">78.38 (46.18-110.59)</td>
                  <td align="center">13.56 (8.62-21.37)</td>
                  <td align="center">23.28 (15.19-35.71)</td>
                  <td align="center">37.83 (24.84-57.66)</td>
                  <td align="center">58.81 (38.63-89.63)</td>
                  <td align="center">94.08 (61.80-143.37)</td>
                  <td align="center">155.30 (102.02-236.67)</td>
                  <td align="center">273.05 (179.36-416.09)</td>
                  <td align="center">466.67 (306.54-711.13)</td>
                </tr>
                <tr>
                  <td align="center">2040</td>
                  <td align="center">69.90 (0-152.48)</td>
                  <td align="center">12.35 (3.44-44.46)</td>
                  <td align="center">21.20 (6.13-73.40)</td>
                  <td align="center">34.45 (10.18-116.68)</td>
                  <td align="center">52.89 (15.77-177.51)</td>
                  <td align="center">83.52 (24.96-279.82)</td>
                  <td align="center">139.11 (41.57-466.15)</td>
                  <td align="center">240.41 (71.84-805.53)</td>
                  <td align="center">410.59 (122.69-1375.73)</td>
                </tr>
                <tr>
                  <td>Relative percent change</td>
                  <td> </td>
                  <td align="center">-17.36%</td>
                  <td align="center">-18.96%</td>
                  <td align="center">-21.80%</td>
                  <td align="center">-22.55%</td>
                  <td align="center">-21.32%</td>
                  <td align="center">-21.28%</td>
                  <td align="center">-18.38%</td>
                  <td align="center">-14.29%</td>
                  <td align="center">-12.11%</td>
                </tr>
                <tr>
                  <td> </td>
                  <td>EAPC</td>
                  <td> </td>
                  <td align="center">-1.07 (-1.10a-1.04)</td>
                  <td align="center">-2.77 (-3.02a-2.52)</td>
                  <td align="center">-2.75 (-2.97a-2.52)</td>
                  <td align="center">-2.72 (-2.94a-2.51)</td>
                  <td align="center">-2.67 (-2.87a-2.47)</td>
                  <td align="center">-2.57 (-2.75a-2.39)</td>
                  <td align="center">-2.41 (-2.57a-2.26)</td>
                  <td align="center">-2.27 (-2.42a-2.12)</td>
                  <td align="center">-2.11 (-2.28a-1.96)</td>
                </tr>
                <tr>
                  <td rowspan="4">
                    <bold>PAD</bold>
                  </td>
                  <td>Observed data</td>
                  <td align="center">2021</td>
                  <td align="center">1.82 (1.73-1.91)</td>
                  <td align="center">0.13 (0.09-0.20)</td>
                  <td align="center">0.27 (0.20-0.38)</td>
                  <td align="center">0.58 (0.46-0.73)</td>
                  <td align="center">1.28 (1.09-1.50)</td>
                  <td align="center">2.38 (2.10-2.71)</td>
                  <td align="center">4.05 (3.62-4.53)</td>
                  <td align="center">7.12 (6.46-7.85)</td>
                  <td align="center">12.08 (11.03-13.24)</td>
                </tr>
                <tr>
                  <td rowspan="2">Projected results</td>
                  <td align="center">2030</td>
                  <td align="center">2.01 (0.91, 3.10)</td>
                  <td align="center">0.12 (0.06-0.24)</td>
                  <td align="center">0.26 (0.14-0.48)</td>
                  <td align="center">0.56 (0.31-0.98)</td>
                  <td align="center">1.17 (0.64-2.01)</td>
                  <td align="center">2.34 (1.29-4.00)</td>
                  <td align="center">4.52 (2.50-7.72)</td>
                  <td align="center">8.44 (4.68-14.42)</td>
                  <td align="center">14.92 (8.27-25.49)</td>
                </tr>
                <tr>
                  <td align="center">2040</td>
                  <td align="center">2.02 (0-5.03)</td>
                  <td align="center">0.12 (0.02-0.63)</td>
                  <td align="center">0.26 (0.05-1.24)</td>
                  <td align="center">0.55 (0.11-2.51)</td>
                  <td align="center">1.14 (0.23-5.06)</td>
                  <td align="center">2.28 (0.47-9.94)</td>
                  <td align="center">4.41 (0.90-19.10)</td>
                  <td align="center">8.49 (1.74-36.74)</td>
                  <td align="center">16.23 (3.33-70.24)</td>
                </tr>
                <tr>
                  <td>Relative percent change</td>
                  <td> </td>
                  <td align="center">+10.99%</td>
                  <td align="center">-7.69%</td>
                  <td align="center">-3.70%</td>
                  <td align="center">-5.17%</td>
                  <td align="center">-10.94%</td>
                  <td align="center">-4.20%</td>
                  <td align="center">+8.89%</td>
                  <td align="center">+19.24%</td>
                  <td align="center">+34.35%</td>
                </tr>
                <tr>
                  <td> </td>
                  <td>EAPC</td>
                  <td> </td>
                  <td align="center">0.45 (0.30-0.59)</td>
                  <td align="center">-0.21 (-0.22a-0.21)</td>
                  <td align="center">-0.21 (-0.21a-0.21)</td>
                  <td align="center">-0.21 (-0.21a-0.21)</td>
                  <td align="center">-0.23 (-0.24a-0.23)</td>
                  <td align="center">-0.21 (-0.24a-0.21)</td>
                  <td align="center">0.07 (-0.08-0.07)</td>
                  <td align="center">0.70 (0.45-0.70)</td>
                  <td align="center">1.4 (1.17-1.40)</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN1001">
                <p>Age-standardized and age-specific rates are presented as medians with 95% uncertainty interval for 2030 and 2040 projections, and as crude rates with 95% CIs for the observed year (2021). Relative percentage change and EAPC between 2021 and 2040 are also provided. CI: confidence interval; EAPC: estimated annual percent change; IHD: ischemic heart disease; PAD: peripheral artery disease.</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
        </p>
        <p>
          <fig id="f02001">
            <label>Figure 1</label>
            <caption>
              <title>&#8211; Projected age-standardized mortality rates in Brazil through 2040. Panels A, B, and C depict age-standardized mortality rates (per 100,000 population) for IHD, stroke, and PAD, respectively. Estimates were obtained using Bayesian age-period-cohort models based on observed data from 1990 to 2021. Black dots represent observed values (1990-2021), while the fan plots illustrate projected estimates for 2022-2040. Shaded regions indicate uncertainty intervals: the darker bands represent the interquartile range (25th to 75th percentile), and the lighter bands represent the 95% UI (2.5th to 97.5th percentile). IHD: ischemic heart disease; PAD: peripheral artery disease; UI: uncertainty interval.</title>
            </caption>
            <graphic xlink:href="1678-4170-abc-122-11-e20250189-50189-gf02-en.tif"/></fig>
        </p>
        <p>
          <fig id="f03001">
            <label>Figure 2</label>
            <caption>
              <title>&#8211; Projected change in IHD, stroke, and PAD mortality in Brazil by age group, 2021-2040. This figure shows the EAPC in mortality rates (per 100,000 population) for IHD, stroke, and PAD across 5-year age brackets in Brazil, projected from 2021 to 2040. Bars represent point estimates, and error bars indicate 95% CIs. Full EAPC values by age group and condition are presented in Table 2.</title>
            </caption>
            <attrib>EAPC: estimated annual percentage change; IHD: ischemic heart disease; PAD: peripheral artery disease.</attrib>
            <graphic xlink:href="1678-4170-abc-122-11-e20250189-50189-gf03-en.tif"/></fig>
        </p>
        <p>Between 1990 and 2021, age-standardized IHD mortality declined for both men and women, although rates consistently remained higher in men (Table S1). Between 2021 and 2040, the age-standardized IHD mortality rate is projected to decrease by 25.33% in men but increase by 4.13% in women (Table S2, <xref ref-type="fig" rid="f04001">Figure 3</xref>, and <xref ref-type="fig" rid="f05001">Figure 4</xref>). As shown in <xref ref-type="fig" rid="f05001">Figure 4</xref>, the gap in IHD mortality between men and women is expected to narrow over time.</p>
        <p>
          <fig id="f04001">
            <label>Figure 3</label>
            <caption>
              <title>&#8211; Projected change in ischemic heart disease (IHD), stroke, and peripheral artery disease (PAD) mortality in Brazil through 2040. This figure presents the estimated annual percentage change (EAPC) in age-standardized mortality rates (per 100,000 population) for IHD (Panel A), stroke (Panel B), and PAD (Panel C) between 2021 and 2040. Results are shown for the overall population, as well as disaggregated by sex (men and women).</title>
            </caption>
            <graphic xlink:href="1678-4170-abc-122-11-e20250189-50189-gf04-en.tif"/></fig>
        </p>
        <p>
          <fig id="f05001">
            <label>Figure 4</label>
            <caption>
              <title>&#8211; Projected age-standardized mortality rates in men and women in Brazil through 2040. Panels A, B, and C show age-standardized mortality rates (per 100,000 population) for ischemic heart disease, stroke, and peripheral artery disease, respectively, stratified by sex &#8212; men (red) and women (blue). Dots represent observed data from 1990 to 2021, while lines correspond to projections for 2022-2040 based on Bayesian age-period-cohort models. Solid lines indicate median estimates; dashed lines represent the interquartile range (25th to 75th percentile); and dotted lines reflect the 95% UI (2.5th to 97.5th percentile). UI: uncertainty. interval.</title>
            </caption>
            <graphic xlink:href="1678-4170-abc-122-11-e20250189-50189-gf05-en.tif"/></fig>
        </p>
        <p>Similarly, age-standardized stroke mortality declined substantially from 1990 to 2021 (Table S3, Figure S2). This downward trend is projected to persist through 2040, with an overall reduction of 17.36% in Brazil (<xref ref-type="table" rid="t1001">Table 1</xref>, <xref ref-type="fig" rid="f02001">Figure 1</xref>). Among age groups, the greatest decline is expected in individuals aged 50-54 years (<xref ref-type="table" rid="t1001">Table 1</xref>, Figure S4, <xref ref-type="fig" rid="f03001">Figure 2</xref>).</p>
        <p>From 1990 to 2021, stroke mortality rates decreased in both sexes (Table S3). Between 2021 and 2040, further reductions are projected; however, the decline will be markedly greater among men (30.02%) compared to women (4.51%) (Table S4, <xref ref-type="fig" rid="f04001">Figure 3</xref> and <xref ref-type="fig" rid="f05001">Figure 4</xref>). As illustrated in <xref ref-type="fig" rid="f05001">Figure 4</xref>, the sex gap in stroke mortality is also expected to diminish over time.</p>
        <p>Regarding PAD, the age-standardized mortality rate initially declined between 1990 and 2015, followed by a sharp increase up to 2021 (Table S5, Figure S2). Between 2021 and 2040, PAD mortality in Brazil is projected to rise by 10.99% (<xref ref-type="table" rid="t1001">Table 1</xref>, <xref ref-type="fig" rid="f02001">Figure 1</xref>). Notably, the projected trends vary substantially by age. While a 7.69% decline is anticipated in the 40-44 age group, mortality is expected to increase by 34.35% in those aged 75-79 years (<xref ref-type="table" rid="t1001">Table 1</xref>, Figure S5, <xref ref-type="fig" rid="f03001">Figure 2</xref>).</p>
        <p>The trend of an initial decline followed by a subsequent sharp increase in PAD mortality was observed in both men and women. Throughout the observed period, men consistently exhibited higher PAD mortality rates (Table S5). Between 2021 and 2040, age-standardized PAD mortality is projected to increase by 14.61% in men and 21.99% in women (Table S6, <xref ref-type="fig" rid="f04001">Figure 3</xref> and <xref ref-type="fig" rid="f05001">Figure 4</xref>).</p>
        <p>The <xref ref-type="fig" rid="f01001">Central Illustration</xref> provides a graphical summary of the study&#8217;s key findings and methodological approach.</p>
      </sec>
      <sec sec-type="discussion">
        <title>Discussion</title>
        <p>We examined the observed burden of IHD, stroke, and PAD mortality among Brazilian adults from 1990 to 2021 and fitted models to project future estimates through 2040. Our findings indicate that age-standardized mortality rates for IHD and stroke have steadily declined over the past 3 decades and are projected to continue decreasing. In contrast, PAD mortality is expected to rise between 2021 and 2040, with a disproportionately greater increase among women.</p>
        <p>The observed decline in IHD and stroke mortality since 1990 aligns with prior findings reported by Bastos et al., who noted similar trends but highlighted that improvements were attenuated in socioeconomically vulnerable regions, particularly in North and Northeast Brazil.<sup><xref ref-type="bibr" rid="B20">20</xref></sup> The Brazilian Society of Cardiology (SBC) has also reported continued reductions in IHD and stroke mortality, despite the adverse impact of COVID-19 on cardiovascular outcomes.<sup><xref ref-type="bibr" rid="B3">3</xref>,<xref ref-type="bibr" rid="B21">21</xref></sup> Comparable projections have been published for countries such as the United States, United Kingdom, and Japan.<sup><xref ref-type="bibr" rid="B9">9</xref>,<xref ref-type="bibr" rid="B10">10</xref>,<xref ref-type="bibr" rid="B22">22</xref></sup> Together with our findings, this body of evidence is encouraging, as it suggests that IHD and stroke mortality may continue to decline despite significant population aging.</p>
        <p>However, our study also revealed that the projected decline in stroke mortality will be considerably smaller among older adults. A previous study analyzing U.S. data reported minimal reductions in stroke mortality among individuals aged 65-74, 75-84, and 85 years or older for both sexes.<sup><xref ref-type="bibr" rid="B9">9</xref></sup> These findings underscore the need for targeted stroke prevention and care strategies in older populations. Importantly, IHD and stroke share several modifiable risk factors. A recent meta-analysis involving 50,000 patients showed that approximately one-third of acute stroke patients also have IHD and are at increased risk of myocardial infarction within 1 year following a stroke.<sup><xref ref-type="bibr" rid="B23">23</xref></sup></p>
        <p>In Brazil, effective acute stroke care is challenged by large rural populations and unequal distribution of health care resources. Although dedicated stroke units and fibrinolysis programs have been implemented in several metropolitan centers, access remains limited in rural and underserved regions.<sup><xref ref-type="bibr" rid="B24">24</xref></sup> While existing health care policies have contributed to improvements in IHD and stroke mortality, further efforts are necessary to consolidate these gains &#8212; especially in view of Brazil&#8217;s rapidly aging population.</p>
        <p>Our study also highlights 2 particularly concerning issues: (i) the growing burden of PAD mortality in Brazil, and (ii) significant sex differences in the projected mortality rates for IHD, stroke, and PAD. According to the GBD, the global burden of PAD increased by 72% between 1990 and 2019.<sup><xref ref-type="bibr" rid="B25">25</xref></sup> Projections by the Institute for Health Metrics and Evaluation &#8212; developers of the GBD &#8212; indicate that low- and middle-income countries will bear a disproportionately greater share of this burden.<sup><xref ref-type="bibr" rid="B2">2</xref></sup> Advanced PAD is associated with high rates of lower limb amputation, poor quality of life, substantial morbidity, and elevated 5- to 10-year mortality.<sup><xref ref-type="bibr" rid="B27">27</xref>,<xref ref-type="bibr" rid="B28">28</xref></sup> These outcomes underscore the urgency of implementing public policies focused on early PAD detection and management.</p>
        <p>The second key issue identified is the marked disparity in cardiovascular outcomes between sexes. A study from Spain found that, compared to men, women experienced longer delays in the diagnosis and treatment of acute myocardial infarction.<sup><xref ref-type="bibr" rid="B28">28</xref></sup> In the context of PAD, vascular surgery outcomes are also poorer for women, who are more likely to present with acute limb ischemia.<sup><xref ref-type="bibr" rid="B26">26</xref>,<xref ref-type="bibr" rid="B29">29</xref></sup> According to the 2023 report from the Brazilian Ministry of Health and the SBC, obesity rates are higher among women than men, and women are 44% more likely to have dyslipidemia.<sup><xref ref-type="bibr" rid="B3">3</xref></sup> Higher PAD prevalence and mortality in women may also serve as a surrogate for undiagnosed or untreated atherosclerosis, which is known to be more prevalent in women. Taken together, these findings emphasize the urgent need for targeted health initiatives aimed at addressing the observed sex disparities in cardiovascular outcomes.</p>
        <p>In 2011, Brazil&#8217;s Ministry of Health launched a 10-year strategic plan to reduce non-communicable disease rates. Since then, the country has achieved important gains, including a 30% reduction in smoking prevalence and a 10% increase in physical activity among adults.<sup><xref ref-type="bibr" rid="B30">30</xref></sup> These are significant achievements, considering that approximately 70% of the total burden of CVD is attributable to modifiable risk factors.<sup><xref ref-type="bibr" rid="B2">2</xref></sup> However, as observed in many other countries, Brazil continues to experience rising rates of adult obesity as well as increased prevalence of hypertension, diabetes, and dyslipidemia.<sup><xref ref-type="bibr" rid="B30">30</xref></sup></p>
        <p>In response, the Brazilian government &#8212; alongside the SBC and other medical associations &#8212; introduced a new national CVD plan in 2023, which is currently under review by the Senate.<sup><xref ref-type="bibr" rid="B31">31</xref></sup> This proposed legislation seeks to address current challenges by implementing targeted interventions and establishing a dedicated federal fund to combat CVD. The proposed allocation of this fund includes: 30% for CVD-related research; 15% for public awareness campaigns on cardiovascular risk factors; 30% for training health professionals, particularly in primary care; and 15% for programs aimed at reducing smoking, alcohol consumption, and other modifiable risk factors. Additionally, 10% of the fund would be managed by the Brazilian Federal Council of Medicine to support specialized training in cardiovascular care. Such initiatives could help reverse the recent trends of underinvestment in Brazil&#8217;s public health care system.<sup><xref ref-type="bibr" rid="B32">32</xref></sup></p>
        <p>Improving medication adherence and expanding access to care &#8212; especially by increasing the number and geographic distribution of health professionals trained in preventive cardiology &#8212; are also critical strategies for effectively addressing the national CVD burden.<sup><xref ref-type="bibr" rid="B5">5</xref>,<xref ref-type="bibr" rid="B33">33</xref>,<xref ref-type="bibr" rid="B34">34</xref></sup></p>
        <p>Beyond traditional cardiovascular risk factors, it is essential to recognize the role of environmental exposures, such as air pollution from fine particulate matter, which has been causally linked to CVD. Encouragingly, recent data show that air pollution-related mortality in Brazil declined between 2010 and 2019.<sup><xref ref-type="bibr" rid="B35">35</xref></sup> However, the same study reported that pollution levels in certain regions remained multiple times higher than the limits recommended by the WHO.<sup><xref ref-type="bibr" rid="B35">35</xref></sup> Thus, future policy efforts should not only continue to address conventional CVD risk factors but also expand to include environmental determinants of cardiovascular health.</p>
        <p>Finally, as increasingly discussed within the cardiology community, the development of preventive cardiology guidelines specifically tailored to women is a crucial step toward reducing the sex-based disparities identified in our study.<sup><xref ref-type="bibr" rid="B36">36</xref>-<xref ref-type="bibr" rid="B39">39</xref></sup></p>
        <sec>
          <title>Strengths and limitations</title>
          <p>This study has several limitations that should be acknowledged. Both event rates and mid-year population estimates were obtained from the GBD 2021 dataset. While these data are originally sourced from the SIM, the GBD applies its own modeling procedures. As a result, our findings may differ from studies that directly abstract data from the original source.<sup><xref ref-type="bibr" rid="B40">40</xref>,<xref ref-type="bibr" rid="B41">41</xref></sup> Nevertheless, because the GBD harmonizes data across countries, our results are more readily comparable to international studies.</p>
          <p>Although the SIM routinely conducts quality checks to ensure accuracy, death certification remains the primary source of mortality information. The accuracy of these records may vary, particularly in resource-limited rural regions. However, the GBD methodology is specifically designed to address issues of data completeness and misclassification.</p>
          <p>Our study does not account for individual-level or population-level risk factors. Future trends in IHD, stroke, and PAD mortality may be significantly influenced by changes in these factors. While more aggressive mitigation strategies could reduce future event rates, current trends &#8212; such as rising prevalence of obesity, diabetes, and tobacco use &#8212; could potentially lead to even higher mortality than projected.</p>
          <p>We employed Bayesian APC models to project future mortality estimates. Like all modeling approaches, these require certain assumptions. Although model misspecification remains a possibility, we reported 95% UIs to account for such limitations. Furthermore, public health outcomes are influenced by a broad array of factors &#8212; including political, cultural, migratory, and environmental changes &#8212; many of which cannot be fully captured by the mathematical models used in this study.</p>
        </sec>
      </sec>
      <sec sec-type="conclusions">
        <title>Conclusion</title>
        <p>Based on observed data from 1990 to 2021, age-standardized mortality from IHD and stroke in Brazil is projected to continue declining through 2040. In contrast, age-standardized mortality attributable to PAD is expected to rise substantially over the same period. While the projected reductions in IHD and stroke mortality will be more pronounced among men, the increase in PAD mortality is anticipated to be considerably higher among women. These findings underscore the urgent need for sustained and targeted public health interventions to reduce cardiovascular health disparities, increase awareness, and improve equitable access to evidence-based care across Brazil.</p>
      </sec>
      <sec sec-type="supplementary-material">
        <title>*Supplemental Materials</title>
        <supplementary-material id="suppl01-en">
          <p>For additional information, please click here. <ext-link ext-link-type="uri" xlink:href="https://abccardiol.org/supplementary-material/2025/12212/2025-0189_final_supplemental_section.pdf">https://abccardiol.org/supplementary-material/2025/12212/2025-0189_final_supplemental_section.pdf</ext-link> </p>
          <media mime-subtype="pdf" mimetype="application" xlink:href="https://minio.scielo.br/documentstore/1678-4170/VBdrFFYqYbrqWKfJ65rKdPw/0b0f9e5209bc9501e18a86ca8d4e8a4dc3fb4518.pdf"/>
        </supplementary-material>
      </sec>
    </body>
    <back>
      <fn-group>
        <fn fn-type="other">
          <label>Study association:</label>
          <p> This study is not associated with any thesis or dissertation work.</p>
        </fn>
        <fn fn-type="other">
          <label>Ethics approval and consent to participate:</label>
          <p> This article does not contain any studies with human participants or animals performed by any of the authors.</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">
          <label>Data Availability Statement:</label>
          <p> GBD 2021 data is accessible from <ext-link ext-link-type="uri" xlink:href="https://vizhub.healthdata.org/gbd-results/">https://vizhub.healthdata.org/gbd-results/</ext-link>. Researchers may register and download data free of charge from this platform. All data used in this study &#8212; including mortality counts and mid-year population estimates &#8212; along with the R scripts used for analysis, have been deposited in a publicly available GitHub repository: <ext-link ext-link-type="uri" xlink:href="https://github.com/svd09/Brazil_CVD">https://github.com/svd09/Brazil_CVD</ext-link>. Alternatively, interested readers may request a zipped archive of all materials by contacting the corresponding author.</p>
        </fn>
        <fn fn-type="financial-disclosure">
          <label>Sources of funding:</label>
          <p> There were no external funding sources for this study.</p>
        </fn>
      </fn-group>
    </back>
  </sub-article>
</article>
