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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">KMwTr87djVtYQRFtMLx8T5t</article-id>
      <article-id specific-use="previous-pid" pub-id-type="publisher-id">S0066-782X2021005013202</article-id>
      <article-id specific-use="scielo-v2" pub-id-type="publisher-id">S0066-782X2021001200615</article-id>
      <article-id pub-id-type="publisher-id">abc.20200435</article-id>
      <article-id pub-id-type="doi">10.36660/abc.20200435</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Artigo Original</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Escore de Risco Cl&#237;nico Simples para Prever a Mortalidade P&#243;s-Alta Hospitalar em Pacientes Chineses Hospitalizados por Insufici&#234;ncia Card&#237;aca</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-8896-8176</contrib-id>
          <name>
            <surname>Wang</surname>
            <given-names>Lei</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
          <xref ref-type="fn" rid="fn_ast1">
            <sup>*</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0001-6816-3875</contrib-id>
          <name>
            <surname>Wang</surname>
            <given-names>Li-Qin</given-names>
          </name>
          <xref ref-type="aff" rid="aff2">
            <sup>2</sup>
          </xref>
          <xref ref-type="fn" rid="fn_ast1">
            <sup>*</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0001-7369-6131</contrib-id>
          <name>
            <surname>Gu</surname>
            <given-names>Mo-Li</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0003-3814-8185</contrib-id>
          <name>
            <surname>Li</surname>
            <given-names>Liang</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0003-3778-2782</contrib-id>
          <name>
            <surname>Wang</surname>
            <given-names>Chen</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-2497-629X</contrib-id>
          <name>
            <surname>Xia</surname>
            <given-names>Yun-Feng</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
        </contrib>
      </contrib-group>
      <aff id="aff1">
        <label>1</label>
        <institution content-type="orgdiv2">Departamento de Medicina Geri&#225;trica</institution>
        <institution content-type="orgdiv1">Fourth Medical Center</institution>
        <institution content-type="orgname">Chinese PLA General Hospital</institution>
        <addr-line>
          <named-content content-type="city">Beijng</named-content>
        </addr-line>
        <country country="CN">China</country>
        <institution content-type="original">Departamento de Medicina Geri&#225;trica, the Fourth Medical Center, Chinese PLA General Hospital, Beijng - China</institution>
      </aff>
      <aff id="aff2">
        <label>2</label>
        <institution content-type="orgdiv2">Departamento de Enfermagem</institution>
        <institution content-type="orgdiv1">Eighth Medical Center</institution>
        <institution content-type="orgname">Chinese PLA General Hospital</institution>
        <addr-line>
          <named-content content-type="city">Beijng</named-content>
        </addr-line>
        <country country="CN">China</country>
        <institution content-type="original">Departamento de Enfermagem, the Eighth Medical Center, Chinese PLA General Hospital, Beijng - China</institution>
      </aff>
      <author-notes>
        <corresp id="c01"> Correspond&#234;ncia: Xia Yunfeng &#8226; Fourth Medical Center of PLA General Hospital - No.51 Fucheng Road, Haidian District Beijing 100048 &#8211; China E-mail: <email>yunfengxia111@163.com</email> </corresp>
        <fn fn-type="equal" id="fn_ast1">
          <label>*</label>
          <p> Os autores contribu&#237;ram igualmente para esse artigo</p>
        </fn>
        <fn fn-type="con">
          <p>Contribui&#231;&#227;o dos autores</p>
          <p>Concep&#231;&#227;o e desenho da pesquisa e Reda&#231;&#227;o do manuscrito: Wang L, Yun-Feng X; Obten&#231;&#227;o de dados: Li-Qin W, Mo-Li G; An&#225;lise e interpreta&#231;&#227;o dos dados: Li Liang; An&#225;lise estat&#237;stica: Li-Qin W, Li Liang, Wang C; Obten&#231;&#227;o de financiamento: Mo-Li G, Wang C; Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do intelectual importante: Wang L, Mo-Li G, Li Liang, Yun-Feng X.</p>
        </fn>
        <fn fn-type="conflict">
          <p>Potencial conflito de interesse</p>
          <p>N&#227;o h&#225; conflito com o presente artigo</p>
        </fn>
      </author-notes>
      <pub-date date-type="pub" publication-format="electronic">
        <day>13</day>
        <month>08</month>
        <year>2021</year>
      </pub-date>
      <pub-date date-type="collection" publication-format="electronic">
        <month>10</month>
        <year>2021</year>
      </pub-date>
      <volume>117</volume>
      <issue>4</issue>
      <fpage>615</fpage>
      <lpage>623</lpage>
      <history>
        <date date-type="received">
          <day>07</day>
          <month>05</month>
          <year>2020</year>
        </date>
        <date date-type="rev-recd">
          <day>10</day>
          <month>09</month>
          <year>2020</year>
        </date>
        <date date-type="accepted">
          <day>04</day>
          <month>11</month>
          <year>2020</year>
        </date>
      </history>
      <permissions>
        <license license-type="open-access" xlink:href="https://creativecommons.org/licenses/by/4.0/" xml:lang="en">
          <license-p> This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. </license-p>
        </license>
      </permissions>
      <abstract>
        <title>Resumo</title>
        <sec>
          <title>Fundamento</title>
          <p> Doen&#231;as cardiovasculares s&#227;o a principal causa de morte na China. Entretanto, os esfor&#231;os atuais para se identificar os fatores de risco de morte em pacientes hospitalizados com insufici&#234;ncia card&#237;aca (IC) est&#227;o direcionados principalmente para a mortalidade durante a interna&#231;&#227;o e a mortalidade ap&#243;s 30 dias nos Estados Unidos. Dessa forma, &#233; necess&#225;rio um modelo semelhante ao modelo utilizado para prever o risco considerado para procedimentos cir&#250;rgicos cardiovasculares em pacientes para avaliar o risco de pacientes internados com diagn&#243;stico de IC.</p>
        </sec>
        <sec>
          <title>Objetivo</title>
          <p> Identificar vari&#225;veis que podem prever a mortalidade por IC um ano ap&#243;s a alta hospitalar, e desenvolver um escore de risco para avaliar o risco de morte no per&#237;odo de um ano.</p>
        </sec>
        <sec>
          <title>M&#233;todos</title>
          <p> No presente estudo, 1.742 pacientes chineses com IC foram divididos aleatoriamente em dois grupos: um grupo de amostra de deriva&#231;&#227;o e um grupo de amostra de teste. O m&#233;todo de simula&#231;&#227;o Monte Carlo via Cadeias de Markov foi usado para identificar vari&#225;veis que podem prever a mortalidade um ano ap&#243;s a alta hospitalar. Vari&#225;veis com uma frequ&#234;ncia &gt;1% na an&#225;lise bivariada, e que foram consideradas clinicamente significativas, foram qualificadas para an&#225;lises de modelagens posteriores. A probabilidade posterior de que uma vari&#225;vel estava estat&#237;stica e significativamente associada ao resultado foi calculada como o n&#250;mero total de vezes em que o IC de 95% da vari&#225;vel n&#227;o coincidiu com 1 (ou seja, o ponto de refer&#234;ncia), dividido pelo n&#250;mero total de itera&#231;&#245;es. Uma vari&#225;vel com uma probabilidade de 0,9 ou mais alta foi considerado um fator de risco robusto para prever o resultado, e foi inclu&#237;da na lista final de vari&#225;veis. O n&#237;vel de signific&#226;ncia estat&#237;stica adotado foi 5%.</p>
        </sec>
        <sec>
          <title>Resultados</title>
          <p> Cinco vari&#225;veis que pudessem prever de maneira robusta a mortalidade um ano ap&#243;s a alta hospitalar foram identificadas: idade, sexo feminino, escore da <italic>New York Heart Association</italic> (Associa&#231;&#227;o de Cardiologia de Nova Iorque) &gt;3, di&#226;metro do &#225;trio esquerdo, e &#237;ndice de massa corporal. Os modelos de deriva&#231;&#227;o e de teste tiveram uma &#225;rea de curva caracter&#237;stica de opera&#231;&#227;o do receptor de 0,79. Essas vari&#225;veis selecionadas foram utilizadas para avaliar o escore de risco de mortalidade por IC ap&#243;s um ano, e este foi dividido em tr&#234;s grupos (baixo, moderado e alto). O grupo de alto risco corresponde a aproximadamente 86% das mortes, e o grupo de risco moderado corresponde a 12% das mortes.</p>
        </sec>
        <sec>
          <title>Conclus&#227;o</title>
          <p> Um escore de risco de 5 vari&#225;veis simples pode ser utilizado para avaliar a mortalidade um ano ap&#243;s a alta hospitalar de pacientes internados com IC.</p>
        </sec>
      </abstract>
      <kwd-group xml:lang="pt">
        <kwd>Insufici&#234;ncia Card&#237;aca</kwd>
        <kwd>Pontua&#231;&#227;o de Propens&#227;o</kwd>
        <kwd>Mortalidade</kwd>
        <kwd>Alta Hospitalar</kwd>
        <kwd>Epidemiologia</kwd>
      </kwd-group>
      <counts>
        <fig-count count="6"/>
        <table-count count="6"/>
        <equation-count count="0"/>
        <ref-count count="21"/>
        <page-count count="9"/>
      </counts>
    </article-meta>
  </front>
  <body>
    <sec sec-type="intro">
      <title>Introdu&#231;&#227;o</title>
      <p>Doen&#231;as cardiovasculares s&#227;o a principal causa de morte na China, correspondendo a aproximadamente 22,5% de todas as mortes.<sup><xref ref-type="bibr" rid="B1">1</xref></sup> A insufici&#234;ncia card&#237;aca (IC) &#233; a d&#233;cima-segunda principal causa de interna&#231;&#227;o hospitalar na China, e quatro milh&#245;es de chineses sofrem dessa doen&#231;a.<sup><xref ref-type="bibr" rid="B1">1</xref></sup> No geral, a IC na China tem um progn&#243;stico especialmente ruim, com at&#233; 40% dos pacientes morrendo por IC no per&#237;odo de um ano.<sup><xref ref-type="bibr" rid="B1">1</xref></sup> A carga financeira da IC tamb&#233;m &#233; consider&#225;vel.<sup><xref ref-type="bibr" rid="B2">2</xref></sup></p>
      <p>Entretanto, os esfor&#231;os atuais para se identificar os fatores de risco de morte em pacientes hospitalizados por IC, tais como o escore de risco de Framingham, est&#227;o voltados principalmente para a mortalidade durante a interna&#231;&#227;o hospitalar<sup><xref ref-type="bibr" rid="B3">3</xref> , <xref ref-type="bibr" rid="B4">4</xref></sup> e a mortalidade ap&#243;s 30 dias nos Estados Unidos.<sup><xref ref-type="bibr" rid="B5">5</xref> , <xref ref-type="bibr" rid="B6">6</xref></sup> Como a IC &#233; uma doen&#231;a cr&#244;nica, a identifica&#231;&#227;o dos fatores de risco de mortalidade de pacientes com IC no longo prazo poderia beneficiar os pacientes. Um modelo semelhante ao modelo utilizado para prever o risco considerado para procedimentos cir&#250;rgicos cardiovasculares em pacientes pode ser utilizado para avaliar o risco de pacientes internados com diagn&#243;stico de IC.<sup><xref ref-type="bibr" rid="B7">7</xref></sup> Considerando-se o aumento da carga de IC na China, &#233; importante encontrar meios para a estratifica&#231;&#227;o de pacientes com base no risco, no momento do diagn&#243;stico inicial e no momento da alta. Al&#233;m disso, como a popula&#231;&#227;o asi&#225;tica representa aproximadamente 5% da popula&#231;&#227;o dos Estados Unidos e a popula&#231;&#227;o chinesa representa 20% da popula&#231;&#227;o mundial, os escores de risco desenvolvidos com base em popula&#231;&#245;es ocidentais geralmente estimam incorretamente o risco para popula&#231;&#245;es asi&#225;ticas.<sup><xref ref-type="bibr" rid="B8">8</xref></sup> Portanto, &#233; importante desenvolver ferramentas clinicamente relevantes para chineses e outros grupos asi&#225;ticos. Uma ferramenta que pudesse especificamente indicar a probabilidade de mortalidade ap&#243;s um ano em pacientes chineses com IC teria grande utilidade cl&#237;nica, pois teria o potencial de orientar a tomada de decis&#227;o cl&#237;nica e de identificar pacientes que t&#234;m mais probabilidade de precisar de um monitoramento p&#243;s-alta intenso. Al&#233;m disso, como a ra&#231;a, a etnia, e o pa&#237;s de origem t&#234;m um grande impacto nos resultados cl&#237;nicos, &#233; importante desenvolver uma avalia&#231;&#227;o de risco espec&#237;fica para o grupo de interesse, ou seja, os pacientes chineses com IC.</p>
      <p>O presente estudo tem o objetivo de identificar fatores de risco que est&#227;o mais fortemente correlacionados &#224; mortalidade ap&#243;s um ano entre pacientes chineses com IC, e de desenvolver um escore de risco simples para avaliar o risco de mortalidade um ano ap&#243;s a alta hospitalar nesses pacientes.</p>
    </sec>
    <sec sec-type="methods">
      <title>M&#233;todos</title>
      <sec>
        <title>Sujeitos</title>
        <p>O presente estudo foi aprovado pelo Comit&#234; de &#201;tica de nosso hospital, e todos os pacientes assinaram o termo de consentimento informado.</p>
        <p>O coorte do estudo foi extra&#237;do do <italic>Beijing Monitoring Heart Failure Patients and Building Heart Failure Management Network Study</italic> (Estudo de monitoramento de pacientes com insufici&#234;ncia card&#237;aca e de constru&#231;&#227;o de rede de gest&#227;o da insufici&#234;ncia card&#237;aca de Pequim), que incluiu todos os pacientes com idade &#8805;20 anos hospitalizados por IC em dos 14 hospitais designados em Pequim, na China, entre 10 de outubro de 2015 e 9 de outubro de 2017. Esses pacientes foram divididos aleatoriamente em dois grupos usando um m&#233;todo de tabela aleat&#243;ria: um grupo de amostra de deriva&#231;&#227;o e um grupo de amostra de teste. As informa&#231;&#245;es sobre mortalidade ap&#243;s um ano foram obtidas por entrevistas telef&#244;nicas p&#243;s-alta hospitalar.</p>
      </sec>
      <sec>
        <title>Candidatas a vari&#225;veis de risco e vari&#225;veis de resultado</title>
        <p>As candidatas a vari&#225;veis de risco inclu&#237;ram as caracter&#237;sticas demogr&#225;ficas (idade, sexo, e &#237;ndice de massa corporal [IMC]), hist&#243;rico m&#233;dico e comorbidades, fatores de estilo de vida, cirurgias card&#237;acas pr&#233;vias, achados cl&#237;nicos e resultados de testes laboratoriais. A idade e o IMC foram medidos como vari&#225;veis cont&#237;nuas, enquanto sexo foi codificado como feminino (sim/n&#227;o). O hist&#243;rico m&#233;dico incluiu hist&#243;rico de infarto do mioc&#225;rdio agudo (IMA), hist&#243;rico de IC, e hist&#243;rico de doen&#231;a card&#237;aca coron&#225;ria (DCC), diabetes tipo I ou tipo II, e hipertens&#227;o. Cirurgias card&#237;acas pr&#233;vias inclu&#237;ram cirurgias de v&#225;lvula anteriores. Os achados cl&#237;nicos inclu&#237;ram o escore de classifica&#231;&#227;o funcional da <italic>New York Heart Association</italic> (NYHA) (classe &gt;3) e fra&#231;&#227;o de eje&#231;&#227;o ventricular esquerda (&lt;40%). Fatores de estilo de vida inclu&#237;ram hist&#243;rico de tabagismo, tabagismo atual e consumo de &#225;lcool. Os dados de testes laboratoriais inclu&#237;ram a frequ&#234;ncia card&#237;aca, a press&#227;o arterial, e o di&#226;metro do &#225;trio esquerdo (em mil&#237;metros), que foi medido como vari&#225;vel cont&#237;nua.</p>
        <p>A vari&#225;vel de resultado foi a mortalidade por IC um ano ap&#243;s a alta hospitalar, definida como morte por qualquer causa que tenha ocorrido ap&#243;s uma interna&#231;&#227;o hospitalar por IC registrada. As informa&#231;&#245;es sobre mortalidade foram obtidas por meio de entrevistas telef&#244;nicas com esses pacientes. A &#250;ltima entrevista foi realizada em 19 de fevereiro de 2019. Se um paciente tivesse morrido dentro de um ano ap&#243;s a alta, a data da morte era obtida de familiares. Pacientes foram exclu&#237;dos da amostra do estudo quando nem eles, nem seus familiares puderam ser contactados.</p>
      </sec>
      <sec>
        <title>An&#225;lise estat&#237;stica</title>
        <p>Os dados do grupo de amostra de deriva&#231;&#227;o e o grupo de amostra de teste foram comparados pelo teste qui-quadrado em rela&#231;&#227;o &#224;s vari&#225;veis categ&#243;ricas e testes t n&#227;o pareados em rela&#231;&#227;o &#224;s vari&#225;veis cont&#237;nuas. Em seguida, o julgamento cl&#237;nico e a an&#225;lise de correla&#231;&#227;o bivariada de Spearman foram utilizados para identificar candidatas a vari&#225;veis que possam estar associadas &#224; mortalidade um ano ap&#243;s a alta hospitalar. Vari&#225;veis com uma frequ&#234;ncia &gt;1% na an&#225;lise bivariada, e que foram consideradas clinicamente significativas, foram qualificadas para an&#225;lises de modelagens posteriores. Para as observa&#231;&#245;es em que faltavam dados, foi criada uma vari&#225;vel dummy para atribuir um valor de 0 quando o valor da vari&#225;vel estava presente, e um valor de 1 quando a vari&#225;vel n&#227;o estava presente. Em seguida, os valores que faltavam foram substitu&#237;dos pela mediana dos valores presentes daquela vari&#225;vel cont&#237;nua, e as vari&#225;veis cont&#237;nuas e dummy foram inclu&#237;das no modelo. Esse m&#233;todo para modelagem dos dados faltantes considerou que esses dados faltavam aleatoriamente, e permitiu a inclus&#227;o de todos os casos dispon&#237;veis, embora n&#227;o tenha sido t&#227;o eficiente quanto procedimentos de imputa&#231;&#227;o m&#250;ltipla.</p>
        <p>O m&#233;todo de simula&#231;&#227;o Monte Carlo via Cadeias de Markov (MCMC) foi usado juntamente com a t&#233;cnica de regress&#227;o log&#237;stica para identificar um conjunto final de fatores de risco que podem prever a mortalidade por IC um ano ap&#243;s a alta hospitalar. As simula&#231;&#245;es foram feitas com 10.000 itera&#231;&#245;es para a amostra de deriva&#231;&#227;o, e um modelo log&#237;stico foi ajustado a cada itera&#231;&#227;o, produzindo um conjunto de vari&#225;veis que s&#227;o &#8220;estatisticamente significativas&#8221;, ou associadas ao resultado. Dessa forma, 10.000 itera&#231;&#245;es da simula&#231;&#227;o produziram 10.000 conjuntos de raz&#245;es de chance (RC) e intervalos de confian&#231;a (IC) de 95%, indicando o n&#237;vel de signific&#226;ncia da associa&#231;&#227;o de cada vari&#225;vel com o resultado. A probabilidade posterior de que uma vari&#225;vel estava estatisticamente e significativamente associada ao resultado foi calculada como o n&#250;mero total de vezes em que o IC de 95% da vari&#225;vel n&#227;o coincidiu com 1 (ou seja, o ponto de refer&#234;ncia), dividido pelo n&#250;mero total de itera&#231;&#245;es. Uma vari&#225;vel com uma probabilidade de 0,9 ou mais alto foi considerado um fator de risco robusto para prever o resultado, e foi inclu&#237;do na lista final de vari&#225;veis. Esse m&#233;todo foi utilizado em outros estudos.<sup><xref ref-type="bibr" rid="B9">9</xref></sup> A &#225;rea sob a curva caracter&#237;stica de opera&#231;&#227;o do receptor (ROC) foi calculada para cada modelo ajustado por itera&#231;&#227;o, para se avaliar seu poder discriminat&#243;rio.<sup><xref ref-type="bibr" rid="B10">10</xref></sup></p>
      </sec>
      <sec>
        <title>Desenvolvimento do escore de risco</title>
        <p>Com base nos resultados da simula&#231;&#227;o, foi constru&#237;do um escore de risco simples, baseado em vari&#225;veis selecionadas para avaliar a mortalidade ap&#243;s um ano. Cada vari&#225;vel foi ponderada utilizando-se o coeficiente padronizado (CP) espec&#237;fico da vari&#225;vel obtido de um modelo log&#237;stico baseado na amostra de deriva&#231;&#227;o original, com a mortalidade ap&#243;s um ano como resultado, e as vari&#225;veis selecionadas como vari&#225;veis independentes. O CP, que mediu a mudan&#231;a de coeficiente para uma altera&#231;&#227;o de desvio padr&#227;o (DP) na vari&#225;vel independente, teve o objetivo de representar a import&#226;ncia relativa da vari&#225;vel independente num modelo de regress&#227;o. Isso permite fazer a compara&#231;&#227;o entre vari&#225;veis independentes utilizando-se unidades comuns. O escore de risco para cada observa&#231;&#227;o, nas amostras de deriva&#231;&#227;o e de valida&#231;&#227;o, foi calculado como: Escore = &#8721; Peso<sub>i</sub> &#8901; Vari&#225;vel<sub>i</sub>, em que peso<sub>i</sub> = SC<sub>i</sub> / &#8721; |SC|, e i = 1, 2, 3, &#8230;, n&#250;mero total de vari&#225;veis selecionadas finais. Em seguida, cada peso foi redimensionado por 100 para permitir que o escore seja uma pr&#225;tica de f&#225;cil utiliza&#231;&#227;o, com exce&#231;&#227;o do peso da idade, que &#233; dimensionado apenas em 10. Cada peso foi posteriormente arredondado para cima ou para baixo, at&#233; seu n&#250;mero inteiro mais pr&#243;ximo em intervalos de 5 (por exemplo, 32,5 para 30,0, ou 18,0 para 20,0). A idade foi arredondada para baixo at&#233; seu patamar mais pr&#243;ximo, com um ponto decimal. Por &#250;ltimo, uma base de 100 foi adicionada ao risco para garantir que n&#227;o houvesse valores negativos nos escores. Para validar e testar esse escore de risco, dois modelos log&#237;sticos foram ajustados. Um modelo utilizou vari&#225;veis individuais que foram selecionadas na simula&#231;&#227;o MCMC como vari&#225;veis independentes, e o outro modelo utilizou o escore de risco como vari&#225;vel independente. Esses dois modelos foram ajustados com amostras de deriva&#231;&#227;o e de teste, e os valores de r quadrado e ROC foram calculados de ambos os modelos para avaliar o desempenho do escore de risco. Todos os testes estat&#237;sticos foram bilaterais e tiveram um n&#237;vel de signific&#226;ncia de 5%, e todas as an&#225;lises foram realizadas utilizando-se a o software SAS vers&#227;o 9.3 vers&#227;o de 64 bits (SAS Institute Inc., Cary, Carolina do Norte, EUA). Todas as vari&#225;veis cont&#237;nuas foram distribu&#237;das normalmente como testadas pelos testes de Shapiro-Wilk. As vari&#225;veis cont&#237;nuas com distribui&#231;&#227;o normal s&#227;o descritas utilizando-se m&#233;dia e desvio padr&#227;o.</p>
      </sec>
    </sec>
    <sec sec-type="results">
      <title>Resultados</title>
      <sec>
        <title>Caracter&#237;sticas do paciente</title>
        <p>O coorte final do estudo incluiu um total de 1.742 pacientes com IC. Entre esses pacientes, as amostras de deriva&#231;&#227;o e de teste inclu&#237;ram 882 e 860 pacientes, respectivamente. A idade m&#233;dia (DP) do coorte foi de 57,0 (12,5) anos, e 9,5% desses pacientes tinham 40 anos de idade ou menos, enquanto 30,9% desses pacientes tinham idade igual ou superior a 65 anos. Al&#233;m disso, 19,9% desses pacientes eram mulheres. As caracter&#237;sticas dos pacientes nas amostras de deriva&#231;&#227;o e de valida&#231;&#227;o eram compar&#225;veis ( <xref ref-type="table" rid="t1">Tabela 1</xref> ). N&#227;o houve diferen&#231;as significativas entre esses dois grupos em termos de idade, sexo, di&#226;metro do &#225;trio esquerdo, frequ&#234;ncia card&#237;aca, FEVE &lt;40 (%), IMA (%), NYHA &gt;3 (%), DCC (%), DM (%), HTN (%), cirurgia de v&#225;lvula (%), hist&#243;rico de tabagismo (%), consumo de &#225;lcool (%), e mortalidade ap&#243;s um ano (%). Entretanto, n&#227;o houve diferen&#231;as significativas entre esses dois grupos em termos de frequ&#234;ncia card&#237;aca &gt;100 (%) e IC (%). N&#227;o houve diferen&#231;as significativas em termos de medicamentos e consultas m&#233;dicas durante o acompanhamento, nem diferen&#231;as significativas em resultados de testes laboratoriais entre todos os pacientes.</p>
        <p>
          <table-wrap id="t1">
            <label>Tabela 1</label>
            <caption>
              <title>&#8211; Caracter&#237;sticas de linha de base da popula&#231;&#227;o do estudo</title>
            </caption>
            <table frame="hsides" rules="groups">
              <colgroup>
                <col/>
                <col/>
                <col/>
                <col/>
                <col/>
              </colgroup>
              <thead>
                <tr>
                  <th align="left">Caracter&#237;sticas do paciente</th>
                  <th>Geral (n=1742)</th>
                  <th>Amostra de deriva&#231;&#227;o (n=882)</th>
                  <th>Amostra de teste (n=860)</th>
                  <th>Valor de p</th>
                </tr>
              </thead>
              <tbody>
                <tr>
                  <td>Dados demogr&#225;ficos Idade, m&#233;dia (DP) anos</td>
                  <td align="center">57,1 (12,4)</td>
                  <td align="center">57,0 (12,4)</td>
                  <td align="center">57,1 (12,5)</td>
                  <td align="center">0,9295</td>
                </tr>
                <tr>
                  <td>Idade faltante, n=4 (%)</td>
                  <td align="center">0,2</td>
                  <td align="center">0,2</td>
                  <td align="center">0,2</td>
                  <td align="center">0,9798</td>
                </tr>
                <tr>
                  <td>Feminino (%)</td>
                  <td align="center">19,9</td>
                  <td align="center">19,8</td>
                  <td align="center">19,9</td>
                  <td align="center">0,9823</td>
                </tr>
                <tr>
                  <td>IMC, m&#233;dia (DP)</td>
                  <td align="center">25,1 (3,4)</td>
                  <td align="center">25,1 (3,4)</td>
                  <td align="center">25,0 (3,4)</td>
                  <td align="center">0,3455</td>
                </tr>
                <tr>
                  <td>IMC faltante, n=0 (%)</td>
                  <td align="center">0</td>
                  <td align="center">0</td>
                  <td align="center">0</td>
                  <td> </td>
                </tr>
                <tr>
                  <td>
                    <bold>Achados cl&#237;nicos e testes laboratoriais</bold>
                  </td>
                  <td> </td>
                  <td> </td>
                  <td> </td>
                  <td> </td>
                </tr>
                <tr>
                  <td>Di&#226;metro do &#225;trio esquerdo (mm), m&#233;dia (DP)</td>
                  <td align="center">39,9 (7,9)</td>
                  <td align="center">40,0 (8,1)</td>
                  <td align="center">39,9 (7,7)</td>
                  <td align="center">0,823</td>
                </tr>
                <tr>
                  <td>Tamanho do &#225;trio esquerdo faltante, n=66 (%)</td>
                  <td align="center">3,8</td>
                  <td align="center">4,2</td>
                  <td align="center">3,1</td>
                  <td align="center">0,1611</td>
                </tr>
                <tr>
                  <td>Frequ&#234;ncia card&#237;aca, m&#233;dia (DP)</td>
                  <td align="center">73,0 (14,0)</td>
                  <td align="center">73,3 (14,8)</td>
                  <td align="center">72,7 (13,2)</td>
                  <td align="center">0,8762</td>
                </tr>
                <tr>
                  <td>Frequ&#234;ncia card&#237;aca faltante, n=12 (%)</td>
                  <td align="center">0,7</td>
                  <td align="center">0,5</td>
                  <td align="center">0,9</td>
                  <td align="center">0,2291</td>
                </tr>
                <tr>
                  <td>Frequ&#234;ncia card&#237;aca &gt;100 (%)</td>
                  <td align="center">4,5</td>
                  <td align="center">5,6</td>
                  <td align="center">3,4</td>
                  <td align="center">0,0276</td>
                </tr>
                <tr>
                  <td>FEVE &lt;40 (%)</td>
                  <td align="center">35,5</td>
                  <td align="center">35,8</td>
                  <td align="center">35,1</td>
                  <td align="center">0,7564</td>
                </tr>
                <tr>
                  <td>FEVE faltante, n=0(%)</td>
                  <td align="center">0</td>
                  <td align="center">0</td>
                  <td align="center">0</td>
                  <td> </td>
                </tr>
                <tr>
                  <td>
                    <bold>Hist&#243;rico m&#233;dico</bold>
                  </td>
                  <td> </td>
                  <td> </td>
                  <td> </td>
                  <td> </td>
                </tr>
                <tr>
                  <td>IC (%)</td>
                  <td align="center">18,1</td>
                  <td align="center">20,2</td>
                  <td align="center">15,8</td>
                  <td align="center">0,0177</td>
                </tr>
                <tr>
                  <td>IMA (%)</td>
                  <td align="center">22,6</td>
                  <td align="center">23,4</td>
                  <td align="center">21,9</td>
                  <td align="center">0,4557</td>
                </tr>
                <tr>
                  <td>NYHA &gt;3(%)</td>
                  <td align="center">42,7</td>
                  <td align="center">42,6</td>
                  <td align="center">42,8</td>
                  <td align="center">0,9461</td>
                </tr>
                <tr>
                  <td>DCC (%)</td>
                  <td align="center">71,2</td>
                  <td align="center">70,4</td>
                  <td align="center">72,0</td>
                  <td align="center">0,4699</td>
                </tr>
                <tr>
                  <td>DM (%)</td>
                  <td align="center">27,8</td>
                  <td align="center">27,2</td>
                  <td align="center">28,4</td>
                  <td align="center">0,5885</td>
                </tr>
                <tr>
                  <td>TxC (%)</td>
                  <td align="center">63,6</td>
                  <td align="center">62,7</td>
                  <td align="center">64,5</td>
                  <td align="center">0,4258</td>
                </tr>
                <tr>
                  <td>Cirurgia de v&#225;lvula (%)</td>
                  <td align="center">6,1</td>
                  <td align="center">6,8</td>
                  <td align="center">5,4</td>
                  <td align="center">0,2044</td>
                </tr>
                <tr>
                  <td>
                    <bold>Estilo de vida</bold>
                  </td>
                  <td> </td>
                  <td> </td>
                  <td> </td>
                  <td> </td>
                </tr>
                <tr>
                  <td>Tabagismo (%)</td>
                  <td align="center">57,8</td>
                  <td align="center">57,6</td>
                  <td align="center">57,9</td>
                  <td align="center">0,8956</td>
                </tr>
                <tr>
                  <td>Consumo de &#225;lcool (%)</td>
                  <td align="center">35,1</td>
                  <td align="center">34,5</td>
                  <td align="center">35,8</td>
                  <td align="center">0,5561</td>
                </tr>
                <tr>
                  <td>Mortalidade ap&#243;s um ano (%)</td>
                  <td align="center">6,5</td>
                  <td align="center">7,3</td>
                  <td align="center">5,8</td>
                  <td align="center">0,2236</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN1">
                <p>
                  <italic>NYHA: Escore de classifica&#231;&#227;o funcional da New York Heart Association, IMC: &#205;ndice de massa corporal, DCC: Doen&#231;a card&#237;aca coron&#225;ria, IC: Insufici&#234;ncia card&#237;aca, IMA: Infarto do mioc&#225;rdio agudo, DM: Diabetes tipo I ou tipo II, HTN: Hipertens&#227;o. Dados cont&#237;nuos foram analisados por teste t. Dados categ&#243;ricos foram analisados por teste qui-quadrado. P&lt;0,05 &#233; significativo.</italic>
                </p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
        </p>
      </sec>
      <sec>
        <title>Vari&#225;veis de risco para previs&#227;o da mortalidade por IC ap&#243;s um ano</title>
        <p>Os &#237;ndices de mortalidade ap&#243;s um ano observados nas amostras de deriva&#231;&#227;o e valida&#231;&#227;o foram 7,3% e 5,8%, respectivamente (p = 0,2236). A <xref ref-type="fig" rid="f01">Figura 1</xref> apresenta a probabilidade de que cada vari&#225;vel seja associada &#224; mortalidade por IC ap&#243;s um ano. Cinco vari&#225;veis, incluindo idade, sexo feminino, IMC, di&#226;metro do &#225;trio esquerdo, e classe NYHA &gt;3, tinham uma probabilidade de 0,9 ou mais alta de associa&#231;&#227;o significativa com a mortalidade ap&#243;s um ano. Elas foram identificadas como as vari&#225;veis finais ( <xref ref-type="fig" rid="f01">Figuras 1a</xref> e <xref ref-type="fig" rid="f01">1b</xref> ). A <xref ref-type="table" rid="t2">Tabela 2</xref> ilustra as RC, CP, e IC de 95% para cada uma das cinco vari&#225;veis selecionadas no conjunto de dados de deriva&#231;&#227;o. A &#225;rea sob a curva ROC desse modelo baseado em 5 vari&#225;veis foi 0,789, com um r quadrado de 0,1761 e uma bondade do ajuste de 0,9013. A capacidade preditiva variou de 0,04, no decil mais baixo, a 0,43 no decil mais alto, indicando que o modelo tem bom poder discriminat&#243;rio ( <xref ref-type="fig" rid="f01">Figura 1c</xref> ). Esse modelo tamb&#233;m se comportou de maneira semelhante ao conjunto de dados de teste ( <xref ref-type="fig" rid="f01">Figura 1d</xref> e <xref ref-type="table" rid="t3">Tabela 3</xref> ).</p>
        <p>
          <fig id="f01">
            <label>Figura 1</label>
            <caption>
              <title>&#8211; <italic>Sele&#231;&#227;o vari&#225;vel e desenvolvimento de modelo para escore de risco.</italic></title>
            </caption>
            <graphic xlink:href="1678-4170-abc-117-04-0615-00435-gf01.tif"/></fig>
        </p>
        <p>
          <table-wrap id="t2">
            <label>Tabela 2</label>
            <caption>
              <title>&#8211; Fatores de risco e pesos correspondentes no escore de risco cl&#237;nico</title>
            </caption>
            <table frame="hsides" rules="groups">
              <colgroup>
                <col/>
                <col/>
                <col/>
                <col/>
                <col/>
                <col/>
                <col/>
              </colgroup>
              <thead>
                <tr>
                  <th align="left">Caracter&#237;sticas do paciente</th>
                  <th>Probabilidade posterior*</th>
                  <th>Raz&#245;es de chance (IC 95%)</th>
                  <th>Coeficiente padronizado</th>
                  <th>Peso inicial</th>
                  <th>Dire&#231;&#227;o</th>
                  <th>Peso redimensionado</th>
                </tr>
              </thead>
              <tbody>
                <tr>
                  <td>Idade, anos</td>
                  <td align="center">0,969</td>
                  <td align="center">1,03 (1.01-1.05)</td>
                  <td align="center">0,1864</td>
                  <td align="center">0,155891946</td>
                  <td> </td>
                  <td align="center">1,5</td>
                </tr>
                <tr>
                  <td>Feminino</td>
                  <td align="center">0,02</td>
                  <td align="center">0,44 (0.20-0.97)</td>
                  <td align="center">-0,1796</td>
                  <td align="center">0,150204901</td>
                  <td align="center">(-)</td>
                  <td align="center">-15</td>
                </tr>
                <tr>
                  <td>di&#226;metro do &#225;trio esquerdo (mm)</td>
                  <td align="center">0,993</td>
                  <td align="center">1,05 (1.02-1.09)</td>
                  <td align="center">0,2157</td>
                  <td align="center">0,180396421</td>
                  <td> </td>
                  <td align="center">20</td>
                </tr>
                <tr>
                  <td>IMC</td>
                  <td align="center">0,001</td>
                  <td align="center">0,89 (0.82-0.96)</td>
                  <td align="center">-0,2254</td>
                  <td align="center">0,188508823</td>
                  <td align="center">(-)</td>
                  <td align="center">-20</td>
                </tr>
                <tr>
                  <td>NYHA <underline>&gt;</underline> 3</td>
                  <td align="center">1,000</td>
                  <td align="center">4,2 (2.07-8.34)</td>
                  <td align="center">0,3886</td>
                  <td align="center">0,324997909</td>
                  <td> </td>
                  <td align="center">30</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN2">
                <p>
                  <italic>*Probabilidade posterior de que a caracter&#237;stica aumente a probabilidade de morte por IC ap&#243;s um ano. Uso do escore: Score = 100 + 1.5age &#8211; 15female + 20 leftatrium &#8211; 20 BMI + 30 NYHA_3 em que NYHA_3 denota o escore de classifica&#231;&#227;o funcional da New York Heart Association &gt;3. Considerando uma paciente espec&#237;fica, de 45 anos de idade, do sexo feminino, com IC, IMC de 23, e di&#226;metro do &#225;trio esquerdo de 30, e classifica&#231;&#227;o NYHA =2, o escore de risco de mortalidade um ano p&#243;s-alta hospitalar para essa paciente pode ser calculado utilizando-se a seguinte f&#243;rmula: Escore=100 + 1,5&#215;45 -15&#215;1 + 20&#215;30 - 20&#215;23 + 30&#215;0=322,5. O escore de risco fica entre a faixa de risco baixo e a de risco moderado.</italic>
                </p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
        </p>
        <p>
          <table-wrap id="t3">
            <label>Tabela 3</label>
            <caption>
              <title>&#8211; Desempenho do modelo nos diferentes escores de risco</title>
            </caption>
            <table frame="hsides" rules="groups">
              <colgroup>
                <col/>
                <col/>
                <col/>
                <col/>
                <col/>
                <col/>
                <col/>
              </colgroup>
              <thead>
                <tr>
                  <th align="left" rowspan="2">Amostra</th>
                  <th colspan="3">Modelo baseado em 5 fatores de risco</th>
                  <th colspan="3">Modelo baseado em fatores de risco</th>
                </tr>
                <tr>
                  <th>ROC</th>
                  <th>R-quadrado redimensionado m&#225;ximo</th>
                  <th>Teste de Hosmer e Lemeshow</th>
                  <th>ROC</th>
                  <th>R-quadrado redimensionado m&#225;ximo</th>
                  <th>Teste de Hosmer e Lemeshow</th>
                </tr>
              </thead>
              <tbody>
                <tr>
                  <td>Deriva&#231;&#227;o</td>
                  <td align="center">0,789</td>
                  <td align="center">0,1761</td>
                  <td align="center">0,9013</td>
                  <td align="center">0,75</td>
                  <td align="center">0,1159</td>
                  <td align="center">0,0243</td>
                </tr>
                <tr>
                  <td>Teste</td>
                  <td align="center">0,792</td>
                  <td align="center">0,1514</td>
                  <td align="center">0,3725</td>
                  <td align="center">0,771</td>
                  <td align="center">0,097</td>
                  <td align="center">0,005</td>
                </tr>
                <tr>
                  <td>Geral</td>
                  <td align="center">0,7858</td>
                  <td align="center">0,1589</td>
                  <td align="center">0,5945</td>
                  <td align="center">0,759</td>
                  <td align="center">0,1069</td>
                  <td align="center">0,003</td>
                </tr>
              </tbody>
            </table>
          </table-wrap>
        </p>
      </sec>
      <sec>
        <title>Escore de risco</title>
        <p>O escore de risco foi constru&#237;do utilizando-se as estimativas de CP da <xref ref-type="table" rid="t2">Tabela 2</xref> . A equa&#231;&#227;o de c&#225;lculo tamb&#233;m est&#225; listada na <xref ref-type="table" rid="t2">Tabela 2</xref> . A m&#233;dia (DP) do escore de risco baseado em amostra de deriva&#231;&#227;o foi de 492,5 (177,1), com uma faixa de 89,9-1195,63, e a m&#233;dia (DP) do escore baseado em amostra de teste foi de 493,0, com uma faixa de 89,9-1073,9. A diferen&#231;a em escores m&#233;dios entre as amostras de deriva&#231;&#227;o e de teste n&#227;o era estatisticamente significativa (p = 0,7324). O escore de risco foi utilizado como vari&#225;vel independente para ajustar a um modelo log&#237;stico, o que produziu uma &#225;rea sob a curva ROC de 0,75 e 0,77 para as amostras de deriva&#231;&#227;o e de teste, respectivamente ( <xref ref-type="table" rid="t3">Tabela 3</xref> ). A <xref ref-type="fig" rid="f02">Figura 2</xref> mostra a distribui&#231;&#227;o do escore de risco ( <xref ref-type="fig" rid="f02">Figura 2a</xref> e <xref ref-type="fig" rid="f02">2b</xref> ) e a rela&#231;&#227;o exponencial entre o escore e a probabilidade de mortalidade por IC um ano ap&#243;s a alta hospitalar ( <xref ref-type="fig" rid="f02">Figura 2c</xref> ).</p>
        <p>
          <fig id="f02">
            <label>Figura 2</label>
            <caption>
              <title>&#8211; <italic>Distribui&#231;&#227;o do escore de risco.</italic></title>
            </caption>
            <graphic xlink:href="1678-4170-abc-117-04-0615-00435-gf02.tif"/></fig>
        </p>
        <p>O escore de risco tem boa capacidade preditiva. Com a amostra de deriva&#231;&#227;o, as probabilidades m&#233;dias previstas para mortalidade ap&#243;s um ano foram de 0,15 e 0,07 para aqueles que morreram dentro do per&#237;odo de um ano e aqueles que sobreviveram ap&#243;s o per&#237;odo de um ano, respectivamente. Esse padr&#227;o foi semelhante para a amostra de teste, as probabilidades m&#233;dias previstas para mortalidade ap&#243;s um ano foram de 0,14 e 0,07 para aqueles que morreram e aqueles que sobreviveram, respectivamente. O escore de risco foi dividido em tr&#234;s faixas baseadas em sua distribui&#231;&#227;o: (1) risco baixo, se o escore fosse &lt;300; (2) risco moderado se o escore fosse &#8805;300 e &#8804;800; (3) risco alto se o escore fosse &gt;800. As propor&#231;&#245;es de pacientes em cada um desses tr&#234;s grupos de risco foram as seguintes: 11,7% para grupos de risco baixo, 73,8% para grupos de risco moderado, e 14,5% para grupos de alto risco. A <xref ref-type="fig" rid="f02">Figura 2d</xref> mostra as taxas de mortalidade ap&#243;s um ano por risco de grupo e pelas amostras de deriva&#231;&#227;o e de teste. A <xref ref-type="fig" rid="f03">Figura 3</xref> mostra a distribui&#231;&#227;o da pontua&#231;&#227;o de risco por grupos que morreram e sobreviveram.</p>
        <p>
          <fig id="f03">
            <label>Figura 3</label>
            <caption>
              <title>&#8211; <italic>Distribui&#231;&#227;o do escore de risco entre os grupos de &#243;bito e sobreviventes.</italic></title>
            </caption>
            <graphic xlink:href="1678-4170-abc-117-04-0615-00435-gf03.tif"/></fig>
        </p>
      </sec>
    </sec>
    <sec sec-type="discussion">
      <title>Discuss&#227;o</title>
      <p>O desenvolvimento de um modelo de risco de IC espec&#237;fico para a popula&#231;&#227;o chinesa &#233; importante, considerando-se que os escores de risco existentes, tais como o amplamente utilizado escore de risco de Framingham, s&#227;o desenvolvidos principalmente nos Estados Unidos, e n&#227;o conseguem estimar corretamente o risco em popula&#231;&#245;es asi&#225;ticas.<sup><xref ref-type="bibr" rid="B8">8</xref> - <xref ref-type="bibr" rid="B12">12</xref></sup> O presente estudo desenvolveu e validou um escore de risco de 5 vari&#225;veis simples para avaliar o risco de mortalidade ap&#243;s um ano em pacientes chineses com IC. Esse escore simples pode ser adicionado &#224; avalia&#231;&#227;o atual de pacientes antes da alta hospitalar, para proporcionar uma base para que os m&#233;dicos possam alocar melhor os recursos e identificar pacientes que possam precisar cuidados ap&#243;s a alta. As vari&#225;veis finais identificadas no presente estudo foram consistentes com os fatores de risco identificados em coortes ocidentais. Al&#233;m da idade e da classifica&#231;&#227;o NYHA, que s&#227;o fatores de risco de mortalidade por IC bem conhecidos, identificou-se que o sexo feminino e o IMC s&#227;o fatores de prote&#231;&#227;o dentro do coorte chin&#234;s, consistente com os achados baseados na popula&#231;&#227;o ocidental.<sup><xref ref-type="bibr" rid="B13">13</xref> , <xref ref-type="bibr" rid="B14">14</xref></sup> Da mesma forma, identificou-se que o di&#226;metro do &#225;trio esquerdo estava associado &#224; hospitaliza&#231;&#227;o por IC e morte.<sup><xref ref-type="bibr" rid="B15">15</xref></sup></p>
      <p>O n&#250;mero de pacientes dentro do presente coorte foi semelhante aos escores de risco desenvolvidos para outras popula&#231;&#245;es com IC.<sup><xref ref-type="bibr" rid="B16">16</xref></sup> Al&#233;m disso, em compara&#231;&#227;o com os estudos anteriores, o presente estudo tem v&#225;rios pontos fortes. Primeiramente, diferentemente de estudos anteriores que avaliaram o risco de mortalidade em curto prazo em pacientes com IC, o presente estudo focou em resultados em longo prazo. Segundo, estes presentes resultados s&#227;o espec&#237;ficos para pacientes chineses, j&#225; que n&#227;o s&#227;o derivados de dados obtidos de outros grupos raciais ou &#233;tnicos. Portanto, isto se aplica mais a pacientes chineses, em compara&#231;&#227;o com escores de risco baseados largamente em coortes ocidentais. Por exemplo, o tamanho de efeito entre IMC e mortalidade por IC pode variar entre a popula&#231;&#227;o ocidental e a chinesa, uma vez que a popula&#231;&#227;o chinesa tem um padr&#227;o de gordura corporal diferente do dos grupos populacionais ocidentais. Como resultado, o crit&#233;rio de IMC universal desenvolvidos pela Organiza&#231;&#227;o Mundial de Sa&#250;de (OMS) n&#227;o &#233; adequado para a popula&#231;&#227;o chinesa e outras popula&#231;&#245;es asi&#225;ticas.<sup><xref ref-type="bibr" rid="B17">17</xref> , <xref ref-type="bibr" rid="B18">18</xref></sup> Da mesma forma, o tamanho de efeito entre o di&#226;metro do &#225;trio esquerdo e a mortalidade por IC entre a popula&#231;&#227;o chinesa e a popula&#231;&#227;o ocidental pode variar, mostrando que caucasianos geralmente t&#234;m um di&#226;metro do &#225;trio esquerdo maior.<sup><xref ref-type="bibr" rid="B19">19</xref></sup> Entretanto, estudos e explora&#231;&#245;es posteriores s&#227;o necess&#225;rios para quantificar essas diferen&#231;as. O presente escore foi desenvolvido usando um m&#233;todo estat&#237;stico robusto e foi validado utilizando-se dados adicionais. Tamb&#233;m houve uma alta concord&#226;ncia com os resultados de deriva&#231;&#227;o. Estas cinco presentes vari&#225;veis parecem atender aos crit&#233;rios de vari&#225;vel ideal. Elas n&#227;o s&#227;o afetadas por interpreta&#231;&#245;es cl&#237;nicas, s&#227;o amplamente aceitas, est&#227;o dispon&#237;veis no momento da interna&#231;&#227;o, e podem ser facilmente coletadas.<sup><xref ref-type="bibr" rid="B20">20</xref></sup> Por &#250;ltimo, ao identificar os componentes modific&#225;veis do presente escore de risco, os servi&#231;os de sa&#250;de p&#250;blica podem ser desenvolvidos para resolver esses problemas espec&#237;ficos. Considerando a extraordinariamente grande popula&#231;&#227;o da China, esse escore poderia permitir o uso direcionado de recursos m&#233;dicos e de sa&#250;de p&#250;blica que n&#227;o inevitavelmente limitados.</p>
      <p>O presente estudo tem v&#225;rias limita&#231;&#245;es comumente observadas no desenvolvimento de escores de risco baseados em dados cl&#237;nicos. Isso n&#227;o leva em conta fatores, tais como a qualidade do m&#233;dico e do cuidado hospitalar, influ&#234;ncias socioecon&#244;micas, ou acesso ao cuidado. Os limiares de risco baixo, intermedi&#225;rio e alto foram baseados naquilo que os pesquisadores consideraram ser risco aceit&#225;vel dentro de cada categoria. Al&#233;m disso, informa&#231;&#245;es importantes sobre tratamento, tais como tratamentos farmacol&#243;gicos e por interven&#231;&#227;o, incluindo inibidores de enzima de convers&#227;o de angiotensina, bloqueadores de receptores da angiotensina, betabloqueadores, e diur&#233;ticos, marca-passos biventriculares, e cardioversores desfibriladores implant&#225;veis, n&#227;o foram inclu&#237;dos no modelo. Exames laboratoriais, tais como n&#237;veis de hemoglobina e s&#243;dio, n&#227;o foram inclu&#237;dos no modelo. Finalmente, os pacientes amostrados estavam em 14 hospitais em Pequim, uma das maiores cidades da China. Pode haver diferen&#231;as entre as caracter&#237;sticas e o cuidado desses pacientes com IC em rela&#231;&#227;o a residentes de &#225;reas mais rurais ou remotas, que n&#227;o s&#227;o levados em considera&#231;&#227;o. Esse &#233; um achado que foi observado ao se avaliar o risco cardiovascular na China.<sup><xref ref-type="bibr" rid="B21">21</xref></sup> Al&#233;m disso, 42% dos pacientes t&#234;m classifica&#231;&#227;o NYHA &gt;3, e o &#237;ndice de mortalidade &#233; de apenas 6,5%, o que deve ser avaliado em mais detalhes em detalhes futuros. No entanto, embora v&#225;rios fatores cl&#237;nicos n&#227;o tenham sido incorporados &#224; an&#225;lise, o objetivo do estudo foi desenvolver uma ferramenta simples com vari&#225;veis facilmente defin&#237;veis para ajudar os m&#233;dicos.</p>
      <p>O presente escore pode ser utilizado para identificar pacientes de alto risco para garantir melhor cuidado ap&#243;s a alta. Dessa forma, ele pode ser usado como guia para m&#233;dicos planejarem o cuidado de pacientes com IC, derivado de resultados baseados em evid&#234;ncias de pesquisas relevantes e confi&#225;veis. Portanto, os resultados do presente estudo oferecem uma abordagem ao cuidado de sa&#250;de, que promove a coleta, a interpreta&#231;&#227;o, e a integra&#231;&#227;o de evid&#234;ncias v&#225;lidas, importantes e aplic&#225;veis, que est&#227;o relacionadas ao paciente, s&#227;o observadas pelo cl&#237;nico, e s&#227;o derivadas de pesquisa, al&#233;m do uso dessas evid&#234;ncias para ajudar a tomada de decis&#227;o.</p>
    </sec>
    <sec sec-type="conclusions">
      <title>Conclus&#227;o e direcionamentos futuros</title>
      <p>Foi demonstrado um modelo para desenvolvimento de um escore de risco que &#233; diretamente aplic&#225;vel a pacientes chineses com IC. Isso poderia garantir melhor que fatores gen&#233;ticos e ambientais de um grupo espec&#237;fico sejam levados em considera&#231;&#227;o e possam ser usados como estrutura para o desenvolvimento de escores de riscos em outros grupos raciais e &#233;tnicos.</p>
    </sec>
  </body>
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    <fn-group>
      <fn fn-type="other">
        <p>Vincula&#231;&#227;o acad&#234;mica</p>
        <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">
        <p>Aprova&#231;&#227;o &#233;tica e consentimento informado</p>
        <p>Este estudo foi aprovado pelo Comit&#234; de &#201;tica do Fourth Medical Center of PLA General Hospital sob o n&#250;mero de protocolo 2020KY002-KS001. Todos os procedimentos envolvidos nesse estudo est&#227;o de acordo com a Declara&#231;&#227;o de Helsinki de 1975, atualizada em 2013. O consentimento informado foi obtido de todos os participantes inclu&#237;dos no estudo.</p>
      </fn>
    </fn-group>
    <fn-group>
      <fn fn-type="supported-by">
        <p>Fontes de financiamento: 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-categories>
        <subj-group subj-group-type="heading">
          <subject>Original Article</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>A Simple Clinical Risk Score to Predict Post-Discharge Mortality in Chinese Patients Hospitalized with Heart Failure</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-8896-8176</contrib-id>
          <name>
            <surname>Wang</surname>
            <given-names>Lei</given-names>
          </name>
          <xref ref-type="aff" rid="aff1001">
            <sup>1</sup>
          </xref>
          <xref ref-type="fn" rid="fn_ast1001">
            <sup>*</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0001-6816-3875</contrib-id>
          <name>
            <surname>Wang</surname>
            <given-names>Li-Qin</given-names>
          </name>
          <xref ref-type="aff" rid="aff2001">
            <sup>2</sup>
          </xref>
          <xref ref-type="fn" rid="fn_ast1001">
            <sup>*</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0001-7369-6131</contrib-id>
          <name>
            <surname>Gu</surname>
            <given-names>Mo-Li</given-names>
          </name>
          <xref ref-type="aff" rid="aff1001">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0003-3814-8185</contrib-id>
          <name>
            <surname>Li</surname>
            <given-names>Liang</given-names>
          </name>
          <xref ref-type="aff" rid="aff1001">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0003-3778-2782</contrib-id>
          <name>
            <surname>Wang</surname>
            <given-names>Chen</given-names>
          </name>
          <xref ref-type="aff" rid="aff1001">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-2497-629X</contrib-id>
          <name>
            <surname>Xia</surname>
            <given-names>Yun-Feng</given-names>
          </name>
          <xref ref-type="aff" rid="aff1001">
            <sup>1</sup>
          </xref>
        </contrib>
      </contrib-group>
      <aff id="aff1001">
        <label>1</label>
        <country country="CN">China</country>
        <institution content-type="original">Department of Geriatric Medicine, the Fourth Medical Center,Chinese PLA General Hospital, Beijng - China </institution>
      </aff>
      <aff id="aff2001">
        <label>2</label>
        <country country="CN">China</country>
        <institution content-type="original">Department of Nursing, the Eighth Medical Center, Chinese PLA General Hospital, Beijng - China</institution>
      </aff>
      <author-notes>
        <corresp id="c01001">Mailing Adress: Xia Yunfeng &#8226; Fourth Medical Center of PLA General Hospital - No.51 Fucheng Road, Haidian District Beijing 100048 &#8211; China E-mail: yunfengxia111@163.com</corresp>
        <fn fn-type="equal" id="fn_ast1001">
          <label>*</label>
          <p>The authors contributed equally to this article</p>
        </fn>
        <fn fn-type="con">
          <p>Author Contributions</p>
          <p>Conception and design of the research and Writing of the manuscript: Wang L, Yun-Feng X; Acquisition of data: Li-Qin W, Mo-Li G; Analysis and interpretation of the data: Li Liang; Statistical analysis: Li-Qin W, Li Liang, Wang C; Obtaining financing: Mo-Li G, Wang C; Critical revision of the manuscript for intellectual content: Wang L, Mo-Li G, Li Liang, Yun-Feng X.</p>
        </fn>
        <fn fn-type="conflict">
          <p>Potential Conflict of Interest</p>
          <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>Cardiovascular diseases are the leading causes of death in China. However, present efforts to identify the risk factors for death in patients hospitalized with heart failure (HF) are primarily focused on in-hospital mortality and 30-day mortality in the United States. Thus, a model similar to the model used for predicting the risk in patients considered for cardiovascular surgical procedures is needed to evaluate the risk of the patients admitted with a diagnosis of HF.</p>
        </sec>
        <sec>
          <title>Objective</title>
          <p>To identify variables that can predict post-discharge one-year HF mortality and develop a risk score to assess the risk of dying within one year.</p>
        </sec>
        <sec>
          <title>Methods</title>
          <p>In the present study, 1,742 Chinese patients with HF were randomly divided into two groups: a derivation sample group and a test sample group. A Markov Chain Monte Carlo simulation method was used to identify variables that can predict the one-year post-discharge mortality. Variables with a frequency of &gt;1% in the bivariate analysis and that were considered clinically meaningful were eligible for further modeling analyses. The posterior probability that a variable was statistically and significantly associated with the outcome was calculated as the total number of times that the variable&#8217;s 95% CI did not overlap with 1 (i.e., the reference point) divided by the total number of iterations. A variable with a probability of 0.9 or higher was considered a robust risk factor for predicting the outcome, and this was included in the final variable list. The level of statistical significance adopted was 5%.</p>
        </sec>
        <sec>
          <title>Results</title>
          <p>Five variables that could robustly predict the one-year post-discharge mortality were identified: age, female gender, New York Heart Association functional classification score &gt;3, left atrial diameter, and body mass index. Both derivation and test models had a receiver operating curve area of 0.79. These selected variables were used to assess the one-year HF mortality risk score, and these were divided into three groups (low, moderate, and high). The high-risk group corresponds to nearly 86% of the deaths, while the moderate group corresponds to 12% of the deaths.</p>
        </sec>
        <sec>
          <title>Conclusion</title>
          <p>A simple 5-variable risk score can be used to assess the one-year post-discharge mortality of hospitalized Chinese patients with HF.</p>
        </sec>
      </abstract>
      <kwd-group xml:lang="en">
        <kwd>Heart Failure</kwd>
        <kwd>Propensity Score</kwd>
        <kwd>Mortality</kwd>
        <kwd>Patient Discharge</kwd>
        <kwd>Epidemiology</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <sec sec-type="intro">
        <title>Introduction</title>
        <p>Cardiovascular diseases are the leading causes of death in China, accounting for approximately 22.5% of all deaths.<sup><xref ref-type="bibr" rid="B1">1</xref></sup> Heart failure (HF) is the twelfth leading cause of hospitalization in China, and four million Chinese suffer from this condition.<sup><xref ref-type="bibr" rid="B1">1</xref></sup> Overall, HF in China has an especially poor prognosis, with up to 40% of patients with HF dying within one year.<sup><xref ref-type="bibr" rid="B1">1</xref></sup> The financial burden of HF is also substantial.<sup><xref ref-type="bibr" rid="B2">2</xref></sup></p>
        <p>However, present efforts to identify the risk factors for death in patients hospitalized with HF, such as the Framingham risk score, are primarily focused on in-hospital mortality<sup><xref ref-type="bibr" rid="B3">3</xref> , <xref ref-type="bibr" rid="B4">4</xref></sup> and 30-day mortality in the United States.<sup><xref ref-type="bibr" rid="B5">5</xref> , <xref ref-type="bibr" rid="B6">6</xref></sup> Since HF is a chronic condition, identifying risk factors for the long-term mortality of patients with HF could bring more benefits to patients. A model similar to the model used for predicting the risk in patients considered for cardiovascular surgical procedures can be used to evaluate the risk of the patients admitted with a diagnosis of HF.<sup><xref ref-type="bibr" rid="B7">7</xref></sup> Given the increasing burden of HF in China, it is important to find means to stratify patients based on risk, upon initial diagnosis, and upon discharge. Furthermore, with the Asian population encompassing nearly 5% of the population of the United States and the Chinese population representing 20% of the world&#8217;s population, the risk scores developed based on Western populations often incorrectly estimate the risk for Asian populations.<sup><xref ref-type="bibr" rid="B8">8</xref></sup> Thus, it is important to develop clinically relevant tools for Chinese and other Asian groups. A tool that could specifically provide the likelihood of one-year mortality in Chinese patients with HF would be of great clinical utility because this would have the potential to guide clinical decision-making and identify patients who are more likely to require intensive post-discharge monitoring. Furthermore, given that race, ethnicity, and country of origin have a large impact on clinical outcomes, it is important to develop a risk assessment specific to the group of interest, that is, Chinese patients with HF.</p>
        <p>The present study aimed to identify risk factors that are most strongly correlated with one-year mortality among Chinese patients with HF and develop a simple risk score to assess the risk of one-year post-discharge mortality for these patients.</p>
      </sec>
      <sec sec-type="methods">
        <title>Methods</title>
        <sec>
          <title>Subjects</title>
          <p>The present study has been approved by the Ethics Committee of our hospital, and all patients provided signed written informed consent.</p>
          <p>The study cohort was drawn from the Beijing Monitoring Heart Failure Patients and the Building Heart Failure Management Network Study, which included all patients who were &#8805;20 years of age and hospitalized for HF in one of the 14 designated hospitals in Beijing, China, from October 10, 2015, to October 9, 2017. These patients were randomly assigned into two groups, using a random table method: a derivation sample group and a test sample group. The one-year mortality information was obtained from post-discharge phone interviews.</p>
        </sec>
        <sec>
          <title>Candidate risk variables and outcome variables</title>
          <p>The candidate risk variables included the demographic characteristics (age, gender, and body mass index [BMI]), medical history and comorbidities, lifestyle factors, previous cardiac surgeries, clinical findings, and laboratory test results. Age and BMI were measured as continuous variables, while gender was coded as female (yes/no). The medical history included the history of acute myocardial infarction (AMI), history of HF, and history of coronary heart disease (CHD), Type I or Type II diabetes, and hypertension. The previous cardiac surgeries included previous valve surgery. The clinical findings included the New York Heart Association (NYHA) functional classification score (class &gt;3) and left ventricular ejection fraction (&lt;40%). The lifestyle factors included a history of tobacco use, present use of tobacco, and alcohol consumption. The laboratory test data included heart rate, blood pressure, and left atrial diameter (in millimeters), which was measured as a continuous variable.</p>
          <p>The outcome variable was the one-year post-discharge HF mortality, which was defined as all-cause deaths that occurred after an index HF hospitalization. The mortality information was obtained by phone interviews with these patients. The last interview date was February 19, 2019. If a patient died within one year after discharge, the date of death was obtained from family members. Patients were excluded from the study sample when neither themselves nor their family members could be reached.</p>
        </sec>
        <sec>
          <title>Statistical analysis</title>
          <p>The data of the derivation sample group and test sample group were compared by Chi-square tests for categorical variables and unpaired <italic>t</italic> -tests for continuous variables. Then, clinical judgment and Spearman bivariate correlation analysis were used to identify candidate variables that may be associated with one-year post-discharge mortality. Variables with a frequency of &gt;1% in the bivariate analysis and which were considered clinically meaningful were eligible for further modeling analyses. For observations with missing data, a dummy variable was created to assign a value of 0 when the value of a variable was present, and a value of 1 when the variable was missing. The missing values were then replaced by the median of non-missing values from that continuous variable, and both the dummy and continuous variables were included in the model. This method of modeling the missing data assumed that these data were missing at random, and permitted the inclusion of all available cases, although this was not as efficient as multiple imputation procedures.</p>
          <p>The Markov Chain Monte Carlo (MCMC) simulation method was used in conjunction with the logistic regression technique to identify a set of final risk factors for predicting the one-year post-discharge HF mortality. The simulations were carried out with 10,000 iterations for the derivation sample, and a logistic model was fitted for each iteration, yielding a set of variables that are &#8220;statistically significant,&#8221; or associated with the outcome. Thus, 10,000 iterations of the simulation yielded 10,000 sets of odds ratios (ORs) and 95% confidence intervals (CI), indicating the significance level for each variable&#8217;s association with the outcome. The posterior probability that a variable was statistically and significantly associated with the outcome was calculated as the total number of times that the variable&#8217;s 95% CI did not overlap with 1 (i.e., the reference point) divided by the total number of iterations. A variable with a probability of 0.9 or higher was considered a robust risk factor for predicting the outcome, and this was included in the final variable list. This method has been used elsewhere.<sup><xref ref-type="bibr" rid="B9">9</xref></sup> The area under the receiver operating characteristic (ROC) curve was calculated for each fitted model per iteration to evaluate its discriminating power.<sup><xref ref-type="bibr" rid="B10">10</xref></sup></p>
        </sec>
        <sec>
          <title>Development of risk score</title>
          <p>Based on the simulation results, a simple risk score was constructed based on the variables selected to assess the one-year mortality. Each variable was weighted using the variable-specific standardized coefficient (SC) obtained from a logistic model based on the original derivation sample, with one-year mortality as the outcome and the selected variables as independent variables. The SC, which measured the change in coefficient for one standard deviation (SD) change in the independent variable, was designed to represent the relative importance of the independent variable in a regression model. This allows for the comparison among independent variables using common units. The risk score for each observation in both derivation and validation samples was calculated as: Score = &#8721; Weight<sub>i</sub>&#8901; Variable<sub>i</sub>, where weight<sub>i</sub>= SC<sub>i</sub>/ &#8721; |SC|, and i = 1, 2, 3, &#8230;, total number of the final selected variables. Each weight was then rescaled by 100 to allow the score to be user-friendly in practice, except for the weight for age, which only scales to 10. Each weight was further rounded up or down to its close integer by 5-interval (for example, 32.5 to 30.0, 18.0 to 20.0). Age was rounded down to its close floor with one decimal point. Finally, a base of 100 was added to the score to ensure that there were no negative values in the scores. To validate and test the risk score, two logistic models were fitted. One model used individual variables that were selected from the MCMC simulation as independent variables, while the other model used the risk score as an independent variable. These two models were fitted with both derivation and test samples, and the r-squared and ROC values were calculated from both models to assess the performance of the risk score. All statistical tests were two-sided and had a significance level of 5%, and all analyses were performed using SAS version 9.3 64-bit version (SAS Institute Inc., Cary, North Carolina, USA). All continuous variables were normally distributed as tested by Shapiro&#8211;Wilk tests. Continuous variables with normal distribution are described using mean and standard deviation.</p>
        </sec>
      </sec>
      <sec sec-type="results">
        <title>Results</title>
        <sec>
          <title>Patient characteristics</title>
          <p>The final study cohort included a total of 1,742 patients with HF. Among these patients, the derivation and test samples included 882 patients and 860 patients, respectively. The mean (SD) age of the cohort was 57.0 (12.5) years, and 9.5% of these patients were 40 or younger, while 30.9% of these patients were 65 or older. Furthermore, 19.9% of these patients were women. The characteristics of patients in the derivation and validation samples were comparable ( <xref ref-type="table" rid="t1001">Table 1</xref> ). There were no significant differences between these two groups in terms of age, gender, left atrial diameter, heart rate, LVEF &lt;40 (%), AMI (%), NYHA &gt;3 (%), CHD (%), DM (%), HTN (%), valve surgery (%), smoking history (%), alcohol consumption (%), and one-year mortality (%). However, there were significant differences between these two groups in terms of heart rate &gt;100 (%) and HF (%). There was no significant difference in drugs and medical appointments during the follow-up and no significant difference in lab test results among all patients.</p>
          <p>
            <table-wrap id="t1001">
              <label>Table 1</label>
              <caption>
                <title>&#8211; Baseline characteristics of the study population</title>
              </caption>
              <table frame="hsides" rules="groups">
                <colgroup width="20%">
                  <col/>
                  <col/>
                  <col/>
                  <col/>
                  <col/>
                </colgroup>
                <thead>
                  <tr>
                    <th align="left">Patient characteristics</th>
                    <th>Overall (n=1742)</th>
                    <th>Derivation sample (n=882)</th>
                    <th>Test sample (n=860)</th>
                    <th>P-value</th>
                  </tr>
                </thead>
                <tbody>
                  <tr>
                    <td>Demographics Age, mean (SD) years</td>
                    <td align="center">57.1 (12.4)</td>
                    <td align="center">57.0 (12.4)</td>
                    <td align="center">57.1 (12.5)</td>
                    <td align="center">0.9295</td>
                  </tr>
                  <tr>
                    <td>Age missing, n=4 (%)</td>
                    <td align="center">0.2</td>
                    <td align="center">0.2</td>
                    <td align="center">0.2</td>
                    <td align="center">0.9798</td>
                  </tr>
                  <tr>
                    <td>Female (%)</td>
                    <td align="center">19.9</td>
                    <td align="center">19.8</td>
                    <td align="center">19.9</td>
                    <td align="center">0.9823</td>
                  </tr>
                  <tr>
                    <td>BMI, mean (SD)</td>
                    <td align="center">25.1 (3.4)</td>
                    <td align="center">25.1 (3.4)</td>
                    <td align="center">25.0 (3.4)</td>
                    <td align="center">0.3455</td>
                  </tr>
                  <tr>
                    <td>BMI missing, n=0 (%)</td>
                    <td align="center">0</td>
                    <td align="center">0</td>
                    <td align="center">0</td>
                    <td> </td>
                  </tr>
                  <tr>
                    <td>
                      <bold>Clinical findings, and laboratory test</bold>
                    </td>
                    <td> </td>
                    <td> </td>
                    <td> </td>
                    <td> </td>
                  </tr>
                  <tr>
                    <td>Left atrial diameter (mm), mean (SD)</td>
                    <td align="center">39.9 (7.9)</td>
                    <td align="center">40.0 (8.1)</td>
                    <td align="center">39.9 (7.7)</td>
                    <td align="center">0.823</td>
                  </tr>
                  <tr>
                    <td>Left atrial size missing, n=66 (%)</td>
                    <td align="center">3.8</td>
                    <td align="center">4.2</td>
                    <td align="center">3.1</td>
                    <td align="center">0.1611</td>
                  </tr>
                  <tr>
                    <td>Heart rate, mean (SD)</td>
                    <td align="center">73.0 (14.0)</td>
                    <td align="center">73.3 (14.8)</td>
                    <td align="center">72.7 (13.2)</td>
                    <td align="center">0.8762</td>
                  </tr>
                  <tr>
                    <td>Heart rate missing, n=12 (%)</td>
                    <td align="center">0.7</td>
                    <td align="center">0.5</td>
                    <td align="center">0.9</td>
                    <td align="center">0.2291</td>
                  </tr>
                  <tr>
                    <td>Heart rate &gt;100 (%)</td>
                    <td align="center">4.5</td>
                    <td align="center">5.6</td>
                    <td align="center">3.4</td>
                    <td align="center">0.0276</td>
                  </tr>
                  <tr>
                    <td>LVEF &lt;40 (%)</td>
                    <td align="center">35.5</td>
                    <td align="center">35.8</td>
                    <td align="center">35.1</td>
                    <td align="center">0.7564</td>
                  </tr>
                  <tr>
                    <td>LVEF missing, n=0(%)</td>
                    <td align="center">0</td>
                    <td align="center">0</td>
                    <td align="center">0</td>
                    <td> </td>
                  </tr>
                  <tr>
                    <td>
                      <bold>Medical history</bold>
                    </td>
                    <td> </td>
                    <td> </td>
                    <td> </td>
                    <td> </td>
                  </tr>
                  <tr>
                    <td>HF (%)</td>
                    <td align="center">18.1</td>
                    <td align="center">20.2</td>
                    <td align="center">15.8</td>
                    <td align="center">0.0177</td>
                  </tr>
                  <tr>
                    <td>AMI (%)</td>
                    <td align="center">22.6</td>
                    <td align="center">23.4</td>
                    <td align="center">21.9</td>
                    <td align="center">0.4557</td>
                  </tr>
                  <tr>
                    <td>NYHA &gt;3(%)</td>
                    <td align="center">42.7</td>
                    <td align="center">42.6</td>
                    <td align="center">42.8</td>
                    <td align="center">0.9461</td>
                  </tr>
                  <tr>
                    <td>CHD (%)</td>
                    <td align="center">71.2</td>
                    <td align="center">70.4</td>
                    <td align="center">72.0</td>
                    <td align="center">0.4699</td>
                  </tr>
                  <tr>
                    <td>DM (%)</td>
                    <td align="center">27.8</td>
                    <td align="center">27.2</td>
                    <td align="center">28.4</td>
                    <td align="center">0.5885</td>
                  </tr>
                  <tr>
                    <td>HTN (%)</td>
                    <td align="center">63.6</td>
                    <td align="center">62.7</td>
                    <td align="center">64.5</td>
                    <td align="center">0.4258</td>
                  </tr>
                  <tr>
                    <td>Valve surgery (%)</td>
                    <td align="center">6.1</td>
                    <td align="center">6.8</td>
                    <td align="center">5.4</td>
                    <td align="center">0.2044</td>
                  </tr>
                  <tr>
                    <td>
                      <bold>Lifestyle</bold>
                    </td>
                    <td> </td>
                    <td> </td>
                    <td> </td>
                    <td> </td>
                  </tr>
                  <tr>
                    <td>Smoke (%)</td>
                    <td align="center">57.8</td>
                    <td align="center">57.6</td>
                    <td align="center">57.9</td>
                    <td align="center">0.8956</td>
                  </tr>
                  <tr>
                    <td>Alcohol consumption (%)</td>
                    <td align="center">35.1</td>
                    <td align="center">34.5</td>
                    <td align="center">35.8</td>
                    <td align="center">0.5561</td>
                  </tr>
                  <tr>
                    <td>One-year mortality (%)</td>
                    <td align="center">6.5</td>
                    <td align="center">7.3</td>
                    <td align="center">5.8</td>
                    <td align="center">0.2236</td>
                  </tr>
                </tbody>
              </table>
              <table-wrap-foot>
                <fn id="TFN1001">
                  <p>
                    <italic>NYHA: New York Heart Association functional classification score, BMI: Body mass index, CHD: Coronary heart disease, HF: Heart failure, AMI: Acute myocardial infarction, DM: Type I or Type II diabetes, HTN: Hypertension. Continuous data were analyzed by the t-test. Categorical data were analyzed by the chi-squared test. P&lt;0.05 is significant.</italic>
                  </p>
                </fn>
              </table-wrap-foot>
            </table-wrap>
          </p>
        </sec>
        <sec>
          <title>Risk variables for predicting the one-year HF mortality</title>
          <p>The observed one-year mortality rates for the derivation and validation samples were 7.3% and 5.8%, respectively ( <italic>P</italic> = 0.2236). <xref ref-type="fig" rid="f01001">Figure 1</xref> presents the probability that each variable was associated with one-year HF mortality. Five variables, including age, female gender, BMI, left atrial diameter, and NYHA class &gt;3, had a probability of 0.9 or above for significantly being associated with one-year mortality. These were identified as the final variables ( <xref ref-type="fig" rid="f01001">Figures 1a</xref> and <xref ref-type="fig" rid="f01001">1b</xref> ). <xref ref-type="table" rid="t2001">Table 2</xref> illustrates the OR, SC, and 95% CI for each of the five selected variables in the derivation dataset. The area under the ROC curve of this 5-variable-based model was 0.789, with an r-squared of 0.1761 and a goodness-of-fit of 0.9013. The predictive ability ranged from 0.04 in the lowest decile to 0.43 in the highest decile, indicating that the model had good discrimination ( <xref ref-type="fig" rid="f01001">Figure 1c</xref> ). This model also performed similarly to the test dataset ( <xref ref-type="fig" rid="f01001">Figure 1d</xref> and <xref ref-type="table" rid="t3001">Table 3</xref> ).</p>
          <p>
            <fig id="f01001">
              <label>Figure 1</label>
              <caption>
                <title>&#8211; <italic>Variable selection and model development for risk score</italic></title>
              </caption>
              <graphic xlink:href="1678-4170-abc-117-04-0615-00435-gf01-en.tif"/></fig>
          </p>
          <p>
            <table-wrap id="t2001">
              <label>Table 2</label>
              <caption>
                <title>&#8211; Risk factors and corresponding weights in the clinical risk score</title>
              </caption>
              <table frame="hsides" rules="groups">
                <colgroup width="14%">
                  <col/>
                  <col/>
                  <col/>
                  <col/>
                  <col/>
                  <col/>
                  <col/>
                </colgroup>
                <thead>
                  <tr>
                    <th align="left">Patient characteristics</th>
                    <th>Posterior probability*</th>
                    <th>Odds ratio (95% CI)</th>
                    <th>Standardized coefficient</th>
                    <th>Initial weight</th>
                    <th>Direction</th>
                    <th>Rescaled weight</th>
                  </tr>
                </thead>
                <tbody>
                  <tr>
                    <td>Age, years</td>
                    <td align="center">0.969</td>
                    <td align="center">1.03 (1.01-1.05)</td>
                    <td align="center">0.1864</td>
                    <td align="center">0.155891946</td>
                    <td> </td>
                    <td align="center">1.5</td>
                  </tr>
                  <tr>
                    <td>Female</td>
                    <td align="center">0.02</td>
                    <td align="center">0.44 (0.20-0.97)</td>
                    <td align="center">-0.1796</td>
                    <td align="center">0.150204901</td>
                    <td align="center">(-)</td>
                    <td align="center">-15</td>
                  </tr>
                  <tr>
                    <td>left atrial diameter (mm)</td>
                    <td align="center">0.993</td>
                    <td align="center">1.05 (1.02-1.09)</td>
                    <td align="center">0.2157</td>
                    <td align="center">0.180396421</td>
                    <td> </td>
                    <td align="center">20</td>
                  </tr>
                  <tr>
                    <td>BMI</td>
                    <td align="center">0.001</td>
                    <td align="center">0.89 (0.82-0.96)</td>
                    <td align="center">-0.2254</td>
                    <td align="center">0.188508823</td>
                    <td align="center">(-)</td>
                    <td align="center">-20</td>
                  </tr>
                  <tr>
                    <td>NYHA <underline>&gt;</underline> 3</td>
                    <td align="center">1.000</td>
                    <td align="center">4.2 (2.07-8.34)</td>
                    <td align="center">0.3886</td>
                    <td align="center">0.324997909</td>
                    <td> </td>
                    <td align="center">30</td>
                  </tr>
                </tbody>
              </table>
              <table-wrap-foot>
                <fn id="TFN2001">
                  <p>
                    <italic>*Posterior probability that the characteristic increases the probability of one-year HF death. Use of the score: Score = 100 + 1.5age &#8211; 15female + 20 leftatrium &#8211; 20 BMI + 30 NYHA_3 where NYHA_3 denotes the New York Heart Association functional classification score &gt;3. Giving a particular 45-year-old female HF patient with BMI of 23 and left atrial diameter of 30, and NYHA classification=2, the risk score of one-year post HF discharge mortality for this patient can be calculated as Score=100 + 1.5&#215;45 -15&#215;1 + 20&#215;30 - 20&#215;23 + 30&#215;0=322.5. The risk score is between the low and moderate range.</italic>
                  </p>
                </fn>
              </table-wrap-foot>
            </table-wrap>
          </p>
          <p>
            <table-wrap id="t3001">
              <label>Table 3</label>
              <caption>
                <title>&#8211; Model performance of the different risk scores.</title>
              </caption>
              <table frame="hsides" rules="groups">
                <colgroup width="14%">
                  <col/>
                  <col/>
                  <col/>
                  <col/>
                  <col/>
                  <col/>
                  <col/>
                </colgroup>
                <thead>
                  <tr>
                    <th align="left" rowspan="2" style="font-weight:normal">Sample</th>
                    <th colspan="3" style="font-weight:normal">5-risk factor-based model</th>
                    <th colspan="3" style="font-weight:normal">Risk score-based model</th>
                  </tr>
                  <tr>
                    <th style="font-weight:normal">ROC</th>
                    <th style="font-weight:normal">Max-rescaled R-Square</th>
                    <th style="font-weight:normal">Hosmer and Lemeshow Test</th>
                    <th style="font-weight:normal">ROC</th>
                    <th style="font-weight:normal">Max-rescaled R-Square</th>
                    <th style="font-weight:normal">Hosmer and Lemeshow Test</th>
                  </tr>
                </thead>
                <tbody>
                  <tr>
                    <td>Derivation</td>
                    <td align="center">0.789</td>
                    <td align="center">0.1761</td>
                    <td align="center">0.9013</td>
                    <td align="center">0.75</td>
                    <td align="center">0.1159</td>
                    <td align="center">0.0243</td>
                  </tr>
                  <tr>
                    <td>Test</td>
                    <td align="center">0.792</td>
                    <td align="center">0.1514</td>
                    <td align="center">0.3725</td>
                    <td align="center">0.771</td>
                    <td align="center">0.097</td>
                    <td align="center">0.005</td>
                  </tr>
                  <tr>
                    <td>Overall</td>
                    <td align="center">0.7858</td>
                    <td align="center">0.1589</td>
                    <td align="center">0.5945</td>
                    <td align="center">0.759</td>
                    <td align="center">0.1069</td>
                    <td align="center">0.003</td>
                  </tr>
                </tbody>
              </table>
            </table-wrap>
          </p>
        </sec>
        <sec>
          <title>Risk score</title>
          <p>The risk score was constructed using the SC estimates in <xref ref-type="table" rid="t2001">Table 2</xref> . The calculation equation is also listed in <xref ref-type="table" rid="t2001">Table 2</xref> . The mean (SD) of the derivation sample-based risk score was 492.5 (177.1), with a range of 89.9&#8211;1195.63, and the mean (SD) of the test sample-based score was 493.0, with a range of 89.9&#8211;1,073.9. The difference in mean scores between the derivation and test samples was not statistically significant (p = 0.7324). The risk score was used as the independent variable to fit a logistic model, which yielded an area under the ROC curve of 0.75 and 0.77 for the derivation and test samples, respectively ( <xref ref-type="table" rid="t3001">Table 3</xref> ). <xref ref-type="fig" rid="f02001">Figure 2</xref> shows the distribution of the risk score ( <xref ref-type="fig" rid="f02001">Figures 2a</xref> and <xref ref-type="fig" rid="f02001">2b</xref> ) and the exponential relationship between the score and the probability of one-year post-discharge HF mortality ( <xref ref-type="fig" rid="f02001">Figure 2c</xref> ).</p>
          <p>
            <fig id="f02001">
              <label>Figure 2</label>
              <caption>
                <title>&#8211; <italic>Distribution of risk score.</italic></title>
              </caption>
              <graphic xlink:href="1678-4170-abc-117-04-0615-00435-gf02-en.tif"/></fig>
          </p>
          <p>The risk score has a good predictive ability. With the derivation sample, the mean predicted probabilities of one-year death were 0.15 and 0.07 for those who died within the one-year window and those who survived after the one-year window, respectively. This pattern was similar for the test sample, in which the mean predicted probabilities of one-year death were 0.14 for those who died and 0.07 for those who survived. The risk score was divided into three ranges based on its distribution: (1) low risk if the score was &lt;300; (2) moderate risk if the score was &#8805;300 and &#8804;800; (3) high risk if the score was &gt;800. The proportions of patients in each of these three risk groups were as follows: 11.7% for low-risk groups, 73.8% for moderate-risk groups, and 14.5% for high-risk groups. <xref ref-type="fig" rid="f02001">Figure 2d</xref> shows the one-year mortality rates by risk group, and by the derivation and test samples. <xref ref-type="fig" rid="f03001">Figure 3</xref> shows the distribution of risk score by died and survived groups.</p>
          <p>
            <fig id="f03001">
              <label>Figure 3</label>
              <caption>
                <title>&#8211; <italic>Distribution of risk score by groups of patients who died and who survived.</italic></title>
              </caption>
              <graphic xlink:href="1678-4170-abc-117-04-0615-00435-gf03-en.tif"/></fig>
          </p>
        </sec>
      </sec>
      <sec sec-type="discussion">
        <title>Discussion</title>
        <p>Developing a Chinese-population-specific risk model for HF is important, given that the present risk scores, such as the widely used Framingham risk score, are developed predominantly in the United States, which cannot correctly estimate the risk in Asian populations.<sup><xref ref-type="bibr" rid="B8">8</xref> - <xref ref-type="bibr" rid="B12">12</xref></sup> The present study developed and validated a simple 5-variable risk score for assessing the risk of one-year mortality for Chinese patients with HF. This simple score can be added in the present assessment of patients prior to hospital discharge in order to provide a basis for physicians to better allocate resources and identify patients who may need post-discharge care. The final variables identified from the present study were consistent with the risk factors identified in Western cohorts. In addition to age and the NYHA classification, which are well-known risk factors for HF mortality, it was found that female gender and BMI are protective factors within the Chinese cohort, consistent with findings based on the Western population.<sup><xref ref-type="bibr" rid="B13">13</xref> - <xref ref-type="bibr" rid="B14">14</xref></sup> Similarly, it was found that the left atrial diameter was associated with HF hospitalization and death.<sup><xref ref-type="bibr" rid="B15">15</xref></sup></p>
        <p>The number of patients within the present cohort was similar to risk scores developed for other HF populations.<sup><xref ref-type="bibr" rid="B16">16</xref></sup> Furthermore, compared to the previous studies, the present study has several strengths. First, unlike previous studies that evaluated the short-term risk of mortality in HF patients, the present study focused on long-term outcomes. Second, these present results are specific to Chinese patients because these are not derived from data obtained from other racial or ethnic groups. Therefore, this is more applicable to Chinese patients, when compared to risk scores based largely on Western cohorts. For example, the effect size between the BMI and HF mortality could differ between the Western and Chinese population, because the Chinese population has a different pattern of body fat when compared to the Western population groups. As a result, the universal BMI criteria developed by the World Health Organization (WHO) is not suitable for Chinese and other Asian populations.<sup><xref ref-type="bibr" rid="B17">17</xref> , <xref ref-type="bibr" rid="B18">18</xref></sup> Similarly, the effect size between the left atrial diameter and HF mortality between the Chinese population and the Western population could differ, showing that Caucasians usually have a large left atrial diameter.<sup><xref ref-type="bibr" rid="B19">19</xref></sup> Nevertheless, further studies and explorations are required to quantify such differences. The present score was developed using a robust statistical method and was validated using additional data. There was also a high agreement with the derivation results. These five variables appear to meet the criteria for an ideal variable. These are unaffected by clinical interpretation, widely accepted, available on admission, and easily collected.<sup><xref ref-type="bibr" rid="B20">20</xref></sup> Last, by identifying the modifiable components of the present risk score, public health services can be developed to resolve these specific issues. Given the extraordinarily large population of China, this would allow for the focused use of medical and public health resources that are unavoidably limited.</p>
        <p>The present study has several limitations commonly observed in the development of clinic-based risk scores. This does not take into account such factors as the quality of physician and hospital care, socioeconomic influences, or access to care. The thresholds for low-, intermediate-, and high-risk were based on what the investigators considered was an acceptable risk within each category. In addition, important treatment information, such as pharmacological and interventional treatments, including angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, and diuretics, biventricular pacemakers, and automatic implantable cardioverter-defibrillator devices, were not included in the model. Laboratory evaluations, such as hemoglobin and sodium levels, were also not included in the model. Finally, the patients sampled were from 14 hospitals in Beijing, a major city in China. There may be differences between the characteristics and care of these patients with HF and those residing in more rural or remote areas that are not accounted for, which is a finding that has been observed when assessing cardiovascular risk in China.<sup><xref ref-type="bibr" rid="B21">21</xref></sup> In addition, 42% of patients are NYHA &gt;3, and mortality is only 6.5%, which should be further evaluated in future studies. Nevertheless, although a number of clinical factors were not incorporated into the analysis, the purpose of the study was to develop a simple tool with easy-to-define variables to assist physicians.</p>
        <p>The present score can be used to identify high-risk patients to provide better post-discharge care. As such, this could be employed as a guide for physicians to plan for the care of patients with HF, derived from evidence-based results of relevant and reliable research. Thus, the results of the present study provide an approach to healthcare, which promotes the collection, interpretation, and integration of valid, important, and applicable patient-reported, clinician-observed, and research-derived evidence, and the use of this evidence for better decision-making.</p>
      </sec>
      <sec sec-type="conclusions">
        <title>Conclusion and future directions</title>
        <p>The present study showed a model for developing a risk score that is directly applicable to Chinese patients with HF. This model could better ensure that group-specific genetic and environmental factors are taken into account and can be used as a framework for developing risk scores in other racial and ethnic groups.</p>
      </sec>
    </body>
    <back>
      <fn-group>
        <fn id="fn2001">
          <label/>
          <p>Study Association</p>
        </fn>
        <fn id="fn3001">
          <label/>
          <p>This study is not associated with any thesis or dissertation work.</p>
        </fn>
        <fn id="fn4001">
          <label/>
          <p>Ethics approval and consent to participate</p>
        </fn>
        <fn id="fn5001">
          <label/>
          <p>This study was approved by the Ethics Committee of the Fourth Medical Center of PLA General Hospital under the protocol number 2020KY002-KS001. All the procedures in this study were in accordance with the 1975 Helsinki Declaration, updated in 2013. Informed consent was obtained from all participants included in the study.</p>
        </fn>
      </fn-group>
      <fn-group>
        <fn fn-type="supported-by">
          <p>Sources of Funding: There were no external funding sources for this study.</p>
        </fn>
      </fn-group>
    </back>
  </sub-article>
</article>
