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  <front>
    <journal-meta>
      <journal-id journal-id-type="publisher-id">abc</journal-id>
      <journal-title-group>
        <journal-title>Arquivos Brasileiros de Cardiologia</journal-title>
        <abbrev-journal-title abbrev-type="publisher">Arq. Bras. Cardiol.</abbrev-journal-title>
      </journal-title-group>
      <issn pub-type="ppub">0066-782X</issn>
      <issn pub-type="epub">1678-4170</issn>
      <publisher>
        <publisher-name>Sociedade Brasileira de Cardiologia - SBC</publisher-name>
        <publisher-loc>S&#227;o Paulo, SP, Brazil</publisher-loc>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v3">ycVSsGKFBWmyTZBxhbbmdkd</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v2">S0066-782X2013003100008</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v1">S0066-782X(13)10100500008</article-id>
      <article-id pub-id-type="doi">10.5935/abc.20130185</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Artigos Originais</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Prega cut&#226;nea tricipital como preditor progn&#243;stico na insufici&#234;ncia card&#237;aca ambulatorial</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Zuchinali</surname>
            <given-names>Priccila</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Souza</surname>
            <given-names>Gabriela Corr&#234;a</given-names>
          </name>
          <xref ref-type="aff" rid="aff02"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Alves</surname>
            <given-names>Fernanda Donner</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>d'Almeida</surname>
            <given-names>Karina Sanches Machado</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Goldraich</surname>
            <given-names>L&#237;via Adams</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Clausell</surname>
            <given-names>Nadine Oliveira</given-names>
          </name>
          <xref ref-type="aff" rid="aff02"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Rohde</surname>
            <given-names>Luis Eduardo Paim</given-names>
          </name>
          <xref ref-type="aff" rid="aff02"/>
        </contrib>
      </contrib-group>
      <aff id="aff01">
        <addr-line>
          <named-content content-type="state">Rio Grande do Sul</named-content>
        </addr-line>
        <institution content-type="orgname">Universidade Federal do Rio Grande do Sul</institution>
        <institution content-type="orgdiv1">Programa de p&#243;s gradua&#231;&#227;o em Ci&#234;ncias da Sa&#250;de: Cardiologia e Ci&#234;ncias Cardiovasculares </institution>
        <country country="BR">Brazil</country>
      </aff>
      <aff id="aff02">
        <addr-line>
          <named-content content-type="city">Porto Alegre</named-content>
          <named-content content-type="state">Rio Grande do Sul</named-content>
        </addr-line>
        <institution content-type="orgname">Universidade Federal do Rio Grande do Sul</institution>
        <institution content-type="orgdiv1">Departamento de Medicina Interna </institution>
        <country country="BR">Brazil</country>
      </aff>
      <pub-date date-type="collection" publication-format="electronic">
        <month>11</month>
        <year>2013</year>
      </pub-date>
      <volume>101</volume>
      <issue>5</issue>
      <fpage>434</fpage>
      <lpage>441</lpage>
      <history>
        <date date-type="received">
          <day>11</day>
          <month>09</month>
          <year>2012</year>
        </date>
        <date date-type="accepted">
          <day>05</day>
          <month>02</month>
          <year>2013</year>
        </date>
        <date date-type="rev-recd">
          <day>14</day>
          <month>09</month>
          <year>2012</year>
        </date>
      </history>
      <permissions>
        <license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by-nc/4.0/" xml:lang="en">
          <license-p>This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.</license-p>
        </license>
      </permissions>
      <abstract>
        <p>FUNDAMENTO: A maioria dos estudos relatando o paradoxo da obesidade utiliza &#237;ndice de massa corporal (IMC) para classificar obesidade. Dados avaliando o valor progn&#243;stico de outras medidas indiretas de composi&#231;&#227;o corporal s&#227;o pouco explorados na insufici&#234;ncia card&#237;aca (IC). OBJETIVO: Avaliar a associa&#231;&#227;o entre IMC e outras medidas de composi&#231;&#227;o corporal indiretas com risco de morte por todas as causas na IC. M&#201;TODOS: Par&#226;metros antropom&#233;tricos de composi&#231;&#227;o corporal foram avaliados em 344 pacientes ambulatoriais com fra&#231;&#227;o de eje&#231;&#227;o do ventr&#237;culo esquerdo (FEVE) &lt; 50%, de uma coorte prospectiva seguida durante 30 &#177; 8,2 meses. A sobrevida foi avaliada por curvas de Kaplan-Meier e an&#225;lise de regress&#227;o de risco proporcional de Cox. RESULTADOS: Os pacientes eram predominantemente do sexo masculino, de etiologia n&#227;o-isqu&#234;mica e com disfun&#231;&#227;o sist&#243;lica do VE moderada a grave (FEVE m&#233;dia de 32 &#177; 9%). Prega cut&#226;nea tricipital (PCT) foi o &#250;nico par&#226;metro antropom&#233;trico associado com progn&#243;stico, com valores significativamente menores nos pacientes que morreram (p = 0,047). Uma PCT &gt; 20 mm estava presente em 9% dos pacientes que morreram e em 22% dos vivos (p = 0,027). Na an&#225;lise univariada, creatinina s&#233;rica, FEVE e classe funcional foram associadas ao risco de morte. Na regress&#227;o de Cox, PCT &gt; 20 mm foi o preditor independente mais forte de mortalidade por qualquer causa (hazard ratio: 0,36; IC 95%: 0,13-0,97; p = 0,03). CONCLUS&#195;O: Embora IMC seja o par&#226;metro antropom&#233;trico mais utilizado na pr&#225;tica cl&#237;nica, nossos resultados sugerem que PCT pode ser um melhor preditor de mortalidade em pacientes ambulatoriais com IC.</p>
      </abstract>
      <kwd-group xml:lang="pt" kwd-group-type="author-generated">
        <kwd>Insufici&#234;ncia card&#237;aca</kwd>
        <kwd>&#205;ndice de massa corporal</kwd>
        <kwd>Mortalidade</kwd>
        <kwd>Composi&#231;&#227;o corporal</kwd>
      </kwd-group>
      <pub-date publication-format="electronic" date-type="pub">
        <day>13</day>
        <month>09</month>
        <year>2013</year>
      </pub-date>
    </article-meta>
  </front>
  <body>
    <p>
      <bold>Prega cut&#226;nea tricipital como preditor progn&#243;stico na insufici&#234;ncia card&#237;aca ambulatorial</bold>
    </p>
    <p>
      <bold>Priccila Zuchinali<sup>I</sup>; Gabriela Corr&#234;a Souza<sup>II</sup>; Fernanda Donner Alves<sup>I</sup>; Karina Sanches Machado d'Almeida<sup>I</sup>; L&#237;via Adams Goldraich<sup>I</sup>; Nadine Oliveira Clausell<sup>II</sup>; Luis Eduardo Paim Rohde<sup>II</sup></bold>
    </p>
    <p><sup>I</sup>Programa de p&#243;s gradua&#231;&#227;o em Ci&#234;ncias da Sa&#250;de: Cardiologia e Ci&#234;ncias Cardiovasculares, Universidade Federal do Rio Grande do Sul </p>
    <p><sup>II</sup>Departamento de Medicina Interna, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS - Brasil</p>
    <p>
      <xref ref-type="corresp" rid="end">Correspond&#234;ncia</xref>
    </p>
    <p>
      <bold>RESUMO</bold>
    </p>
    <p><bold>FUNDAMENTO:</bold> A maioria dos estudos relatando o paradoxo da obesidade utiliza &#237;ndice de massa corporal (IMC) para classificar obesidade. Dados avaliando o valor progn&#243;stico de outras medidas indiretas de composi&#231;&#227;o corporal s&#227;o pouco explorados na insufici&#234;ncia card&#237;aca (IC). </p>
    <p><bold>OBJETIVO:</bold> Avaliar a associa&#231;&#227;o entre IMC e outras medidas de composi&#231;&#227;o corporal indiretas com risco de morte por todas as causas na IC. </p>
    <p><bold>M&#201;TODOS:</bold> Par&#226;metros antropom&#233;tricos de composi&#231;&#227;o corporal foram avaliados em 344 pacientes ambulatoriais com fra&#231;&#227;o de eje&#231;&#227;o do ventr&#237;culo esquerdo (FEVE) <underline>&lt;</underline> 50%, de uma coorte prospectiva seguida durante 30 &#177; 8,2 meses. A sobrevida foi avaliada por curvas de Kaplan-Meier e an&#225;lise de regress&#227;o de risco proporcional de Cox. </p>
    <p><bold>RESULTADOS:</bold> Os pacientes eram predominantemente do sexo masculino, de etiologia n&#227;o-isqu&#234;mica e com disfun&#231;&#227;o sist&#243;lica do VE moderada a grave (FEVE m&#233;dia de 32 &#177; 9%). Prega cut&#226;nea tricipital (PCT) foi o &#250;nico par&#226;metro antropom&#233;trico associado com progn&#243;stico, com valores significativamente menores nos pacientes que morreram (p = 0,047). Uma PCT <underline>&gt;</underline> 20 mm estava presente em 9% dos pacientes que morreram e em 22% dos vivos (p = 0,027). Na an&#225;lise univariada, creatinina s&#233;rica, FEVE e classe funcional foram associadas ao risco de morte. Na regress&#227;o de Cox, PCT <underline>&gt;</underline> 20 mm foi o preditor independente mais forte de mortalidade por qualquer causa (hazard ratio: 0,36; IC 95%: 0,13-0,97; p = 0,03). </p>
    <p><bold>CONCLUS&#195;O:</bold> Embora IMC seja o par&#226;metro antropom&#233;trico mais utilizado na pr&#225;tica cl&#237;nica, nossos resultados sugerem que PCT pode ser um melhor preditor de mortalidade em pacientes ambulatoriais com IC.</p>
    <p><bold>Palavras-chave:</bold> Insufici&#234;ncia card&#237;aca; &#205;ndice de massa corporal; Mortalidade; Composi&#231;&#227;o corporal.</p>
    <p>
      <bold>Introdu&#231;&#227;o</bold>
    </p>
    <p>Obesidade &#233; definida pelo excesso de gordura corporal e tem uma rela&#231;&#227;o de longa data com a doen&#231;a cardiovascular (DCV) e insufici&#234;ncia card&#237;aca (IC)<sup>1,2</sup>. Na popula&#231;&#227;o adulta geral livre de DCV, extremos no &#237;ndice de massa corporal (IMC) foram associados com maior risco de mortalidade geral<sup>3-5</sup>. Contudo, h&#225; cada vez mais provas cl&#237;nicas que indicam que o excesso de peso pode proporcionar menor risco de eventos cl&#237;nicos adversos, particularmente em pacientes com IC. Este fen&#244;meno foi denominado como "paradoxo da obesidade" ou "epidemiologia reversa"<sup>6-8</sup>.</p>
    <p>A maioria dos relatos sobre o paradoxo da obesidade t&#234;m utilizado o IMC para classificar a obesidade<sup>9</sup>. Embora o IMC seja o m&#233;todo mais comum para definir popula&#231;&#245;es obesas e com sobrepeso em estudos epidemiol&#243;gicos, ele n&#227;o reflete claramente a composi&#231;&#227;o corporal<sup>10</sup>, reproduzindo uma sensibilidade relativamente baixa para predizer excesso de gordura<sup>11</sup>. Infelizmente, medi&#231;&#245;es diretas da composi&#231;&#227;o da massa corp&#243;rea, como absortometria radiol&#243;gica de dupla energia (DEXA) n&#227;o s&#227;o pr&#225;ticas e n&#227;o foram diretamente relacionadas &#224; sobrevida de pacientes com IC<sup>12</sup>.</p>
    <p>Dados para avaliar o valor progn&#243;stico de outras medidas antropom&#233;tricas indiretas da composi&#231;&#227;o corporal, como a circunfer&#234;ncia da cintura (CC), circunfer&#234;ncia muscular do bra&#231;o (CMB) e prega cut&#226;nea do tr&#237;ceps (PCT), t&#234;m sido pouco examinados em pacientes com IC. Lavie e cols.<sup>13</sup> sugeriram que a porcentagem elevada de gordura corporal, estimada por medidas de pregas cut&#226;neas, pode ser um preditor independente de morte cardiovascular ou transplante card&#237;aco. No entanto, outros estudos n&#227;o chegaram a um consenso sobre o papel destes par&#226;metros no progn&#243;stico da IC<sup>14-16</sup>.</p>
    <p>Portanto, o objetivo deste estudo prospectivo foi avaliar a associa&#231;&#227;o entre IMC e v&#225;rias outras medidas indiretas, mas de f&#225;cil acesso, da composi&#231;&#227;o corporal e risco de mortalidade e hospitaliza&#231;&#227;o por IC. </p>
    <p>
      <bold>M&#233;todos</bold>
    </p>
    <p>
      <bold>Desenho de Estudo e Popula&#231;&#227;o</bold>
    </p>
    <p>Uma coorte prospectiva de pacientes ambulatoriais com IC, acompanhada em uma Cl&#237;nica de IC e Transplante Card&#237;aco de um hospital universit&#225;rio de atendimento terci&#225;rio em Porto Alegre (RS, Brasil), entre maio de 2008 e dezembro de 2009, foi inclu&#237;da no estudo. Esta coorte incluiu pacientes com o diagn&#243;stico de IC, predominantemente com disfun&#231;&#227;o sist&#243;lica do ventr&#237;culo esquerdo [fra&#231;&#227;o de eje&#231;&#227;o ventricular esquerda (FEVE) &lt;50%], confirmada por ecocardiograma bidimensional. Mulheres gr&#225;vidas, pacientes com edema perif&#233;rico significativo, e aqueles com condi&#231;&#245;es cl&#237;nicas que tornavam suas medidas antropom&#233;tricas invi&#225;veis, foram exclu&#237;dos. Todos os pacientes assinaram o termo de consentimento antes da inclus&#227;o e o protocolo de pesquisa foi aprovado pelo comit&#234; de &#233;tica institucional.</p>
    <p>
      <bold>Par&#226;metros Antropom&#233;tricos</bold>
    </p>
    <p>Medidas antropom&#233;tricas de peso, altura, &#225;rea de superf&#237;cie corporal (ASC), IMC, CC, CMB e PCT foram coletadas durante a primeira consulta m&#233;dica. Todas as medidas antropom&#233;tricas foram realizadas pelo mesmo pesquisador treinado, um nutricionista, para evitar variabilidade entre observadores. </p>
    <p>
      <bold>IMC, ASC, e &#205;ndice Ponderal (IP)</bold>
    </p>
    <p>O IMC foi calculado utilizando a equa&#231;&#227;o de Quetelet como segue: IMC (Quetelet) = peso (kg)/altura (m)<sup>2</sup>. O peso foi medido usando-se uma balan&#231;a (Filizola PL 180; Filizola, Brasil) com capacidade de 180 kg e acuidade de 100 g. Para medi&#231;&#227;o da altura, utilizou-se um estadi&#244;metro vertical montado na parede. O IMC foi classificado em tr&#234;s categorias de acordo com a classifica&#231;&#227;o da Organiza&#231;&#227;o Mundial de Sa&#250;de para adultos: desnutri&#231;&#227;o(&lt; 18,5 kg / m<sup>2</sup>), peso eutrofia (18,5-24,9 kg/m<sup>2</sup>) e excesso de peso (&gt; 25 kg / m<sup>2</sup>), e os crit&#233;rios da Organiza&#231;&#227;o Pan-Americana da Sa&#250;de para os idosos: desnutri&#231;&#227;o(&lt;23 kg/m<sup>2</sup>), peso eutrofia (23-28 kg / m<sup>2</sup>) e excesso de peso (&gt;28 kg/m<sup>2</sup>)<sup>17</sup>. Al&#233;m disso, calculamos o ASC como peso<sup>0.5378</sup> x altura<sup>0.3964</sup> &#215; 0,024265 e IP como peso/altura<sup>3</sup>.</p>
    <p>
      <bold>Circunfer&#234;ndia da Cintura</bold>
    </p>
    <p>CC (cm) foi medida no ponto m&#233;dio entre a &#250;ltima costela e a crista il&#237;aca durante a expira&#231;&#227;o. Os pacientes foram instru&#237;dos a permanecer em uma posi&#231;&#227;o ereta com o peso distribu&#237;do uniformemente em ambos os lados e respirando suavemente para evitar a contra&#231;&#227;o do m&#250;sculo abdominal.</p>
    <p>
      <bold>Prega Cut&#226;nea Tricipital</bold>
    </p>
    <p>A espessura da PCT (mm) foi obtida no ponto m&#233;dio do bra&#231;o n&#227;o-dominante (entre o processo acromial e olecr&#226;nio) com o bra&#231;o estirado livremente ao longo do corpo. a prega cut&#226;nea, em seguida, foi pin&#231;ada com os dedos das m&#227;os e um adip&#244;metro cient&#237;fico (Cescorf Scientific, Cescorf, Brasil) foi usado. A medida foi repetida tr&#234;s vezes e a m&#233;dia das medi&#231;&#245;es foi utilizada para a an&#225;lise. </p>
    <p>
      <bold>Circunfer&#234;ncia Muscular do Bra&#231;o</bold>
    </p>
    <p>A CMB (cm) foi calculada atrav&#233;s da medi&#231;&#227;o da circunfer&#234;ncia do bra&#231;o (CB) e a espessura da PCT, usando a seguinte f&#243;rmula proposta por Jelliffe: C1 = C2 - 3.14 * S, em que C1 &#233; a CMB (cm), C2 &#233; a CB (cm), e S &#233; a espessura da PCT (cm)<sup>18</sup>. </p>
    <p>
      <bold>Avalia&#231;&#227;o de Resultados</bold>
    </p>
    <p>Os pacientes inclu&#237;dos foram acompanhados na Cl&#237;nica Ambulatorial de IC e Transplante Card&#237;aco. Na cl&#237;nica de IC, foram agendadas consultas regulares foram agendadas, com intervalos pr&#233;-definidos de 1-4 meses. O acompanhamento foi realizado atrav&#233;s de revis&#227;o de prontu&#225;rio eletr&#244;nico (a maioria dos pacientes teve v&#225;rias consultas durante o per&#237;odo do estudo). Para os pacientes que n&#227;o visitaram regularmente a cl&#237;nica de IC (ou perderam o acompanhamento), foi tentado estabelecer um contato telef&#244;nico com o intuito de obter eventos cl&#237;nicos relevantes com base em uma entrevista estruturada realizada por enfermeiros treinados. Para aqueles que n&#227;o se conseguiu contato telef&#244;nico, o Banco de Dados do Certificado de &#211;bito Estadual foi consultado, o qual cont&#233;m dados sobre a causa principal e a data de todas as mortes em nosso estado. Para a an&#225;lise estat&#237;stica foi utilizado (1) mortalidade por todas as causas e (2) hospitaliza&#231;&#245;es relacionadas a IC. </p>
    <p>
      <bold>An&#225;lise Estat&#237;stica</bold>
    </p>
    <p>Caracter&#237;sticas cl&#237;nicas iniciais do paciente foram expressas em m&#233;dia &#177; DP ou n&#250;mero e porcentagem. As vari&#225;veis cont&#237;nuas foram comparadas pelo teste t de Student ou teste U de Mann-Whitney, conforme apropriado, enquanto que as vari&#225;veis categ&#243;ricas foram comparadas pelo teste do qui-quadrado ou teste exato de Fisher. A PCT e o IMC tamb&#233;m foram analisados segundo quintis da distribui&#231;&#227;o. As curvas de sobrevida foram constru&#237;das usando o m&#233;todo de Kaplan-Meier e comparadas com o teste de Log-Rank. A an&#225;lise de regress&#227;o de riscos proporcionais de Cox foi realizada para determinar os preditores independentes de sobrevida e incluiu pelo menos um par&#226;metro antropom&#233;trico (IMC ou PCT) e preditores cl&#237;nicos de risco [g&#234;nero, idade, classe de acordo com a <italic>New York Heart Association</italic> (NYHA), FEVE, e n&#237;vel s&#233;rico de creatinina]. Um valor de p bicaudal &lt;0,05 foi considerado estatisticamente significativo. An&#225;lises estat&#237;sticas foram realizadas utilizando o <italic>software</italic> estat&#237;stico SPSS ver. 18 para <italic>Windows</italic> (SPSS, Inc., Chicago, IL, EUA).</p>
    <p>
      <bold>Resultados</bold>
    </p>
    <p>De maio de 2008 a setembro de 2009, um total de 378 pacientes ambulatoriais com IC, que foram acompanhados na Cl&#237;nica de Transplante e IC, concordaram em participar do estudo e tiveram seus par&#226;metros antropom&#233;tricos avaliados. Foram exclu&#237;dos 34 pacientes do protocolo, pois a avalia&#231;&#227;o da fun&#231;&#227;o do VE indicou uma FEVE&gt; 50%.</p>
    <p>As caracter&#237;sticas cl&#237;nicas basais da popula&#231;&#227;o restante do estudo (n = 344) s&#227;o apresentadas na <xref ref-type="table" rid="aop_5121tab01">Tabela 1</xref>. Em geral, os pacientes foram predominantemente do sexo masculino, autodeclarados brancos, de etiologia n&#227;o-isqu&#234;mica, na classe funcional I-II na NYHA e com disfun&#231;&#227;o sist&#243;lica do VE de moderada a grave (FEVE m&#233;dia = 32 &#177; 9%). Os pacientes, Em sua maioria, eram hipertensos e 30% tinham diabetes. O per&#237;odo m&#233;dio de acompanhamento foi de 30,3 &#177; 8,2 meses. Os pacientes que morreram eram mais velhos, tinham n&#237;veis relativamente altos de creatinina, menor FEVE, e mostravam uma tend&#234;ncia de maior classe funcional.</p>
    <p content-type="asset">
      <table-wrap id="aop_5121tab01">
        <graphic xlink:href="1678-4170-abc-101-05-0434-30185-gt01.jpg"/></table-wrap>
    </p>
    <p>Par&#226;metros de avalia&#231;&#227;o nutricional est&#227;o listados na <xref ref-type="table" rid="aop_5121tab02">Tabela 2</xref>. A maioria dos pacientes com IC estava com sobrepeso quando foi classificada por IMC. N&#227;o houve diferen&#231;a significativa na maioria dos par&#226;metros antropom&#233;tricos entre pacientes que morreram e os que sobreviveram. Em particular, ASC, o IP e IMC foram muito semelhantes em ambos os grupos, mesmo quando estratificadas por quintis da distribui&#231;&#227;o. PCT foi o &#250;nico &#237;ndice antropom&#233;trico associado com progn&#243;stico de IC. Pacientes que sobreviveram tiveram uma PCT 10% maior do que os pacientes que morreram. A PCT <underline>&gt;</underline> 20 mil&#237;metros foi observada em apenas 9% dos pacientes com IC que morreram durante o seguimento e em 22% daqueles que sobreviveram (p = 0,027; <xref ref-type="table" rid="aop_5121tab02">Tabela 2</xref>).</p>
    <p content-type="asset">
      <table-wrap id="aop_5121tab02">
        <graphic xlink:href="1678-4170-abc-101-05-0434-30185-gt02.jpg"/></table-wrap>
    </p>
    <p>Os dados referentes a quintis de PCT s&#227;o apresentados na <xref ref-type="table" rid="aop_5121tab03">Tabela 3</xref>. Os pacientes dentro do quintil de PCT mais alto eram mais novos, na maior parte mulheres, com n&#237;veis mais baixos de creatinina sangu&#237;nea e FEVE mais elevada. Como esperado, os pacientes no quintil de PCT mais alto tiveram IMC e CC (p &lt;0,001) mais elevados. A <xref ref-type="fig" rid="aop_5121fig01">Figura 1</xref> retrata as taxas de hospitaliza&#231;&#227;o por IC e mortalidade geral de acordo com quintis de PCT. Nossa an&#225;lise demonstrou que pacientes com IC dentro do 5&#186; quintil apresentavam uma taxa de mortalidade aproximadamente tr&#234;s vezes menor do que os pacientes nos 2&#186;, 3&#186; e 4&#186; quintis. N&#227;o foram observadas diferen&#231;as significativas em hospitaliza&#231;&#245;es por IC de acordo com a PCT. Al&#233;m disso, as curvas de sobrevida de Kaplan-Meier estratificadas pela PCT divergiram progressivamente ao longo do tempo (<xref ref-type="fig" rid="aop_5121fig02">Figura 2A</xref>), mas essas diferen&#231;as n&#227;o foram observadas na an&#225;lise estratificada por IMC. </p>
    <p content-type="asset">
      <table-wrap id="aop_5121tab03">
        <graphic xlink:href="1678-4170-abc-101-05-0434-30185-gt03.jpg"/></table-wrap>
    </p>
    <p content-type="asset">
      <fig id="aop_5121fig01">
        <graphic xlink:href="1678-4170-abc-101-05-0434-30185-gf01.jpg"/></fig>
    </p>
    <p content-type="asset">
      <fig id="aop_5121fig02">
        <graphic xlink:href="1678-4170-abc-101-05-0434-30185-gf02.jpg"/></fig>
    </p>
    <p>A <xref ref-type="table" rid="tab04">Tabela 4</xref> mostra os resultados da an&#225;lise univariada e da an&#225;lise de regress&#227;o multivariada de Cox para todas as causas de mortalidade, incluindo os par&#226;metros nutricionais e outras vari&#225;veis cl&#237;nicas. Na an&#225;lise univariada, os n&#237;veis de creatinina s&#233;rica, FEVE, e classe NYHA foram associados com o risco, mas PCT foi o melhor preditor de mortalidade [hazard ratio (HR) = 0,36, intervalo de confian&#231;a de 95% (IC) = 0,14-0,91, p = 0,03]. Finalmente, ap&#243;s o ajuste dessas caracter&#237;sticas cl&#237;nicas, a PCT permaneceu como o maior preditor independente de mortalidade geral (HR = 0,36; 95% IC = 0,13 - 0,97).</p>
    <table-wrap id="tab04">
      <graphic xlink:href="1678-4170-abc-101-05-0434-30185-gt04.jpg"/></table-wrap>
    <p>
      <bold>Discuss&#227;o</bold>
    </p>
    <p>Apesar do crescente interesse no paradoxo da obesidade, ainda h&#225; um debate em curso sobre o par&#226;metro mais adequado para avaliar o estado nutricional de pacientes com IC. Nossos resultados demonstraram que entre os in&#250;meros &#237;ndices antropom&#233;tricos (IMC, ASC, IP, PCT, CC e CB), a PCT foi o &#250;nico par&#226;metro. que pode diferenciar sobreviventes de n&#227;o-sobreviventes em uma coorte prospectiva de pacientes com IC do "mundo real" contempor&#226;neo. Este achado est&#225; de acordo com o conceito de epidemiologia reversa, pois pacientes com IC no quintil mais alto de PCT tiveram mortalidade global mais baixa, mesmo ap&#243;s ajuste para outros importantes preditores cl&#237;nicos de risco. N&#227;o se observou uma rela&#231;&#227;o dose-resposta entre PCT e mortalidade, j&#225; que apenas o quintil superior, representando uma maior quantidade de massa gorda, demonstrou ser um fator protetor independente. Al&#233;m disso, ao contr&#225;rio de outros estudos, o IMC n&#227;o foi um indicador adequado de progn&#243;stico de IC.</p>
    <p>A correla&#231;&#227;o entre o IMC e a sobreviv&#234;ncia da IC permanece controversa. A an&#225;lise <italic>post-hoc</italic> de grande testes<sup>19</sup> cl&#237;nicos demonstrou que o menor IMC foi associado com diminui&#231;&#227;o da sobrevida. Pacientes sintom&#225;ticos com IC avaliados no ensaio <italic>Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity </italic>(Candesartan na Insufici&#234;ncia Card&#237;aca: Avalia&#231;&#227;o da Redu&#231;&#227;o em Mortalidade e Morbidade), com fun&#231;&#227;o sist&#243;lica do VE reduzida ou preservada, pacientes abaixo do peso ou aqueles com um IMC baixo estavam independentemente associados com um consider&#225;vel risco de morte aumentado (quase 70% para IMC &lt;22,5 kg/m<sup>2</sup>), mas principalmente em pacientes sem evid&#234;ncia de sobrecarga l&#237;quida<sup>7</sup>. Recentemente, Casas-Vara e cols. descreveram este fen&#244;meno em pacientes idosos e hospitalizados por IC. Entretanto, embora a obesidade seja frequentemente avaliada pelo IMC na pr&#225;tica cl&#237;nica, v&#225;rios investigadores t&#234;m questionado a precis&#227;o do IMC em avaliar diferentes componentes da composi&#231;&#227;o corporal<sup>21-23</sup>. Por exemplo, a rela&#231;&#227;o entre o IMC e o percentual de gordura corporal &#233; influenciada pela etnia e idade<sup>24</sup>. Nos idosos, o IMC pode representar uma percentagem maior de gordura corporal, enquanto que nos mais jovens, esta associa&#231;&#227;o &#233; menos evidente<sup>25</sup>. Recentemente, de forma semelhante aos nossos achados, v&#225;rios outros investigadores t&#234;m questionado a utilidade do IMC como preditor da mortalidade ou de eventos card&#237;acos<sup>10,14,16,26</sup>. </p>
    <p>&#205;ndices diretos da composi&#231;&#227;o corporal s&#227;o, teoricamente, os melhores marcadores para avaliar o papel progn&#243;stico do estado nutricional em diferentes cen&#225;rios cardiovasculares. Infelizmente, at&#233; agora, n&#227;o existiam estudos prospectivos em larga escala que avaliassem o papel desses par&#226;metros em sobrevida na IC. Recentemente, Oreopoulos e cols. avaliaram a associa&#231;&#227;o entre medidas diretas da composi&#231;&#227;o corporal por DEXA e fatores progn&#243;sticos em 140 pacientes com insufici&#234;ncia card&#237;aca cr&#244;nica e demonstraram que o IMC n&#227;o classificou adequadamente o estado de gordura corporal em aproximadamente 40% dos pacientes estudados. Al&#233;m disso, a massa corporal magra elevada e/ou massa de gordura menor foram independentemente associadas com fatores que s&#227;o prognosticamente ben&#233;ficos na IC, sugerindo que o IMC pode n&#227;o ser um bom indicador da adiposidade e pode, de fato, ser um melhor substituto para a massa corporal magra nesta popula&#231;&#227;o, um achado que por si s&#243; poderia questionar o paradoxo da obesidade<sup>12</sup>. Contudo, tamb&#233;m deve-se considerar que a associa&#231;&#227;o de medi&#231;&#245;es diretas da composi&#231;&#227;o corporal com marcadores substitutos de DCV talvez n&#227;o se traduza em dados semelhantes com rela&#231;&#227;o &#224; sobrevida<sup>10</sup>. </p>
    <p>A antropometria &#233; uma t&#233;cnica simples que pode ser facilmente aplicada na pr&#225;tica cl&#237;nica ou em grandes estudos populacionais. In&#250;meros par&#226;metros antropom&#233;tricos t&#234;m sido propostos para avaliar o estado nutricional e avaliar os diferentes componentes da composi&#231;&#227;o corporal. A medi&#231;&#227;o de espessura da PCT permite o teor da estimativa de gordura corporal<sup>27</sup>, enquanto que as circunfer&#234;ncias dos membros refletem a condi&#231;&#227;o nutricional do m&#250;sculo e, assim, o estado nutricional de prote&#237;nas. &#201; importante salientar que a PCT mede principalmente a gordura subcut&#226;nea e, portanto, n&#227;o &#233; sens&#237;vel a mudan&#231;as ou altera&#231;&#245;es no tecido adiposo visceral. A densidade corporal e gordura corporal podem ser precisamente estimadas a partir da soma das medi&#231;&#245;es das pregas cut&#226;neas. Estudos anteriores t&#234;m comparado e validado diferentes t&#233;cnicas de composi&#231;&#227;o corporal para avaliar a massa adiposa com o DEXA e demonstraram uma adequada precis&#227;o para estimar massa adiposa corporal, tanto para prega subescapular quanto para o PCT<sup>29</sup>. Em particular, a PCT tem sido usada mais frequentemente do que outros locais porque &#233; f&#225;cil de acessar, &#233; reprodut&#237;vel e pode medir uma ampla gama de varia&#231;&#227;o entre indiv&#237;duos, &#233; reproduz&#237;vel e pode medir uma ampla gama de varia&#231;&#227;o entre indiv&#237;duos<sup>30</sup>. Um estudo recente comparou avalia&#231;&#227;o de composi&#231;&#227;o corp&#243;rea em 118 pacientes de hemodi&#225;lise e reportou que PCT foi um dos par&#226;metros mais precisos para estimar porcentagem total de gordura corporal usando DEXA como teste de refer&#234;ncia<sup>31</sup>.</p>
    <p>Lavie e cols.<sup>13</sup> foram os primeiros a avaliar o papel progn&#243;stico do percentual de gordura corporal com base em medi&#231;&#245;es de pregas cut&#226;neas em pacientes com IC e demonstraram que para cada 1% de redu&#231;&#227;o absoluta no percentual de gordura corporal, os principais eventos cl&#237;nicos aumentaram em&gt;13%. A avalia&#231;&#227;o de outros par&#226;metros antropom&#233;tricos, tais como CC, foi proposta para estratifica&#231;&#227;o de risco de IC, mas com resultados inconsistentes<sup>14,15</sup>. Nossos resultados refor&#231;aram o conceito do paradoxo da obesidade e sugeriram que a avalia&#231;&#227;o de um simples par&#226;metro antropom&#233;trico para medir a gordura subcut&#226;nea (PCT) poderia ser adequado para avaliar indiretamente a massa de gordura total no corpo.</p>
    <p>Quanto ao risco de hospitaliza&#231;&#227;o, a maioria dos estudos sobre a avalia&#231;&#227;o do paradoxo da obesidade optou por an&#225;lise de um desfecho combinado (morte e hospitaliza&#231;&#227;o), limitando assim avalia&#231;&#245;es distintas destes eventos. Ademais, alguns estudos encontraram resultados semelhantes, em que a obesidade &#233; um preditor apenas da mortalidade geral/cardiovascular, mas n&#227;o da hospitaliza&#231;&#227;o<sup>8</sup>. Uma poss&#237;vel explica&#231;&#227;o para esses achados &#233; o fato de que os pacientes com adiposidade mais elevada s&#227;o diagnosticados com IC mais precocemente, justificando assim o fato deste grupo ser mais jovem, ter menos grau de disfun&#231;&#227;o card&#237;aca e consequentemente maior sobrevida. Estes pacientes, no entanto, podem ter vulnerabilidade semelhante a epis&#243;dios de descompensa&#231;&#227;o em IC do que aqueles com quantidades normais de massa gorda.</p>
    <p>Os resultados do presente estudo devem ser avaliados considerando algumas limita&#231;&#245;es metodol&#243;gicas. Em primeiro lugar, usamos medidas indiretas da composi&#231;&#227;o corporal para avaliar a massa de gordura corporal. Diversos estudos, por&#233;m, sugerem que a medida PCT &#233; aparentemente uma estimativa adequada da gordura corporal<sup>27</sup>. Em segundo lugar, reconhecemos que a antropometria, principalmente a medi&#231;&#227;o da prega cut&#226;nea, exige uma quantidade consider&#225;vel de habilidade t&#233;cnica e meticulosidade. Em nosso protocolo, todos os par&#226;metros foram avaliados por um &#250;nico profissional treinado para evitar a variabilidade entre observadores. Em terceiro lugar, optamos por utilizar apenas medi&#231;&#245;es PCT para prever a composi&#231;&#227;o da gordura corporal<sup>30,31</sup> em vez de equa&#231;&#245;es mais complexas com base em m&#250;ltiplas pregas cut&#226;neas. Embora esta estrat&#233;gia possa reduzir um pouco a precis&#227;o da avalia&#231;&#227;o da composi&#231;&#227;o corporal, acreditamos que simplifica a aplicabilidade cl&#237;nica de nossos achados.</p>
    <p>
      <bold>Conclus&#227;o</bold>
    </p>
    <p>Nossos resultados demonstraram que a PCT pode ser um melhor preditor de mortalidade em pacientes ambulatoriais com IC e refor&#231;aram o conceito de paradoxo da obesidade. A medi&#231;&#227;o de PCT tem as vantagens de um m&#233;todo simples, pr&#225;tico e de baixo custo para avaliar o risco e pode ser facilmente implementado na pr&#225;tica cl&#237;nica, se realizada por um profissional treinado. </p>
    <p>
      <bold>Contribui&#231;&#227;o dos Autores</bold>
    </p>
    <p>Concep&#231;&#227;o e desenho da pesquisa: Souza GC; Obten&#231;&#227;o de dados: Alves FD, Zuchinali P, Souza GC, Almeida KSM; An&#225;lise e interpreta&#231;&#227;o dos dados: Goldraich LA, Rohde LEP, Zuchinali P; An&#225;lise estat&#237;stica: Goldraich LA, Zuchinali P; Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do intelectual: Clausell NO, Souza GC, Rohde LEP, Zuchinali P.</p>
    <p>
      <bold>Potencial Conflito de Interesses</bold>
    </p>
    <p>Declaro n&#227;o haver conflito de interesses pertinentes.</p>
    <p>
      <bold>Fontes de Financiamento</bold>
    </p>
    <p>O presente estudo n&#227;o teve fontes de financiamento externas.</p>
    <p>
      <bold>Vincula&#231;&#227;o Acad&#234;mica</bold>
    </p>
    <p>N&#227;o h&#225; vincula&#231;&#227;o deste estudo a programas de p&#243;s-gradua&#231;&#227;o.</p>
    <p>
      <fn id="end" fn-type="corresp">
        <label>
          <bold>Correspond&#234;ncia:</bold>
        </label>
        <p> Luis E. Rohde, MD ScD </p>
        <p> Servi&#231;o de Cardiologia, Hospital de Cl&#237;nicas de Porto Alegre </p>
        <p> Ramiro Barcelos 2350, sala 2061 </p>
        <p> Porto Alegre, RS, Brasil 90035-003 </p>
        <p> E-mail: </p>
        <p>
          <email xlink:href="rohde.le@gmail.com">rohde.le@gmail.com</email>
        </p>
      </fn>
    </p>
    <p>Artigo recebido em 11/09/12; revisado em 14/09/12; aceito em 05/02/13.</p>
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  <sub-article article-type="translation" id="TRen" xml:lang="en">
    <front-stub>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Original Articles</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title xml:lang="en">Triceps skinfold as a prognostic predictor in outpatient heart failure</article-title>
      </title-group>
      <abstract xml:lang="en">
        <p>BACKGROUND: Most reports regarding the obesity paradox have focused on body mass index (BMI) to classify obesity and the prognostic values of other indirect measurements of body composition remain poorly examined in heart failure (HF). Objective: To evaluate the association between BMI and other indirect, but easily accessible, body composition measurements associated with the risk of all-cause mortality in HF. METHODS: Anthropometric parameters of body composition were assessed in 344 outpatients with a left ventricular ejection fraction (LVEF) of &lt;50% from a prospective HF cohort that was followed-up for 30 &#177; 8.2 months. Survival was evaluated using the Kaplan-Meier method and Cox proportional hazard regression analysis. RESULTS: HF patients were predominantly male, of non-ischemic etiology, and had moderate to severe LV systolic dysfunction (mean LVEF = 32 &#177; 9%). Triceps skinfold (TSF) was the only anthropometric index that was associated with HF prognosis and had significantly lower values in patients who died (p = 0.047). A TSF &gt; 20 mm was present in 9% of patients that died and 22% of those who survived (p = 0.027). Univariate analysis showed that serum creatinine level, LVEF, and NYHA class were associated with the risk of death, while Cox proportional hazard regression analysis showed that TSF &gt; 20 was a strong independent predictor of all-cause mortality (hazard ratio = 0.36; 95% confidence interval = 0.13-0.97, p = 0.03). CONCLUSION: Although BMI is the most widely used anthropometric parameter in clinical practice, our results suggested that TSF is a better predictive marker of mortality in HF outpatients.</p>
      </abstract>
      <kwd-group xml:lang="en">
        <kwd>Heart failure</kwd>
        <kwd>Body mass index</kwd>
        <kwd>Mortality</kwd>
        <kwd>Body composition</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <p>
        <fn id="enda-body2">
          <label>
            <bold>Triceps skinfold as a prognostic predictor in outpatient heart failure</bold>
          </label>
          <p>
            <bold>Priccila Zuchinali<sup>I</sup>; Gabriela Corr&#234;a Souza<sup>II</sup>; Fernanda Donner Alves<sup>I</sup>; Karina Sanches Machado d'Almeida<sup>I</sup>; L&#237;via Adams Goldraich<sup>I</sup>; Nadine Oliveira Clausell<sup>II</sup>; Luis Eduardo Paim Rohde<sup>II</sup></bold>
          </p>
        </fn>
      </p>
      <p><sup>I</sup>Programa de p&#243;s gradua&#231;&#227;o em Ci&#234;ncias da Sa&#250;de: Cardiologia e Ci&#234;ncias Cardiovasculares, Universidade Federal do Rio Grande do Sul</p>
      <p><sup>II</sup>Departamento de Medicina Interna, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS - Brasil</p>
      <p>Mailing Address</p>
      <p>
        <bold>ABSTRACT</bold>
      </p>
      <p><bold>BACKGROUND:</bold> Most reports regarding the obesity paradox have focused on body mass index (BMI) to classify obesity and the prognostic values of other indirect measurements of body composition remain poorly examined in heart failure (HF).</p>
      <p><bold>Objective:</bold> To evaluate the association between BMI and other indirect, but easily accessible, body composition measurements associated with the risk of all-cause mortality in HF.</p>
      <p><bold>METHODS:</bold> Anthropometric parameters of body composition were assessed in 344 outpatients with a left ventricular ejection fraction (LVEF) of <underline>&lt;</underline>50% from a prospective HF cohort that was followed-up for 30 &#177; 8.2 months. Survival was evaluated using the Kaplan-Meier method and Cox proportional hazard regression analysis. </p>
      <p><bold>RESULTS:</bold> HF patients were predominantly male, of non-ischemic etiology, and had moderate to severe LV systolic dysfunction (mean LVEF = 32 &#177; 9%). Triceps skinfold (TSF) was the only anthropometric index that was associated with HF prognosis and had significantly lower values in patients who died (p = 0.047). A TSF <underline>&gt;</underline> 20 mm was present in 9% of patients that died and 22% of those who survived (p = 0.027). Univariate analysis showed that serum creatinine level, LVEF, and NYHA class were associated with the risk of death, while Cox proportional hazard regression analysis showed that TSF <underline>&gt;</underline> 20 was a strong independent predictor of all-cause mortality (hazard ratio = 0.36; 95% confidence interval = 0.13-0.97, p = 0.03). </p>
      <p><bold>CONCLUSION:</bold> Although BMI is the most widely used anthropometric parameter in clinical practice, our results suggested that TSF is a better predictive marker of mortality in HF outpatients.</p>
      <p><bold>Keywords:</bold> Heart failure; Body mass index; Mortality; Body composition.</p>
      <p>
        <bold>Introduction</bold>
      </p>
      <p>Obesity is defined by excessive body fat and has a long-established relationship with cardiovascular disease (CVD) and heart failure (HF)<sup>1,2</sup>. In the general CVD-free adult population, extremes in body mass index (BMI) have been associated with an increased risk of overall mortality<sup>3-5</sup>. However, there is a growing body of clinical evidence indicating that excess weight might confer a lower risk of adverse clinical events, particularly in HF patients. This phenomenon has been referred to as the "obesity paradox" or "reverse epidemiology"<sup>6-8</sup>. </p>
      <p>Most reports regarding the obesity paradox have used BMI to classify obesity<sup>9</sup>. Although BMI is the most common method to define overweight and obese populations in epidemiological studies, it clearly does not reflect body composition<sup>10</sup>, thus depicting a relatively low sensitivity to predict fat excess<sup>11</sup>. Unfortunately, direct measurements of body mass composition, like dual energy X-ray absorptiometry (DEXA), are not practical and have not been directly related to survival in HF patients<sup>12</sup>.</p>
      <p>Data to evaluate the prognostic value of other anthropometric and indirect measures of body composition, such as waist circumference (WC), arm muscle circumference (AMC), and triceps skinfold (TSF), have been poorly examined in HF patients. Lavie et al<sup>13</sup> have suggested that a high body fat percentage, as estimated by TSF measurements, might be an independent predictor of cardiovascular death or heart transplantation. However, other studies have not reached a consensus regarding the role of these parameters in HF prognosis<sup>14-16</sup>.</p>
      <p>Therefore, the aim of the present prospective study was to evaluate the association between BMI and several other indirect, but easily accessible, body composition measurements to the risk of HF mortality and hospitalization. </p>
      <p>
        <bold>Methods</bold>
      </p>
      <p>
        <bold>Study Design and Population</bold>
      </p>
      <p>A prospective cohort of HF outpatients followed-up at the HF and Transplant Clinic of a university tertiary care hospital in Porto Alegre (RS, Brazil) between May 2008 and December 2009 were enrolled in the present study. This cohort included patients with an HF diagnosis, predominantly with left ventricular systolic dysfunction [left ventricular ejection fraction (LVEF) &lt; 50%], confirmed by two-dimensional echocardiography. Pregnant women, patients with significant peripheral edema, and those with clinical conditions, in which anthropometric measurements were not feasible, were excluded. Signed and informed consent was obtained from all patients prior to enrollment and the research protocol was approved by our institutional review committee.</p>
      <p>
        <bold>Anthropometric Parameters</bold>
      </p>
      <p>Anthropometric measurements of weight, height, body surface area (BSA), BMI, WC, arm circumference (AC), AMC, and TSF were collected during the first medical examination. All anthropometric measurements were performed by the same trained investigator, a registered nutritionist, to avoid interobserver variability. </p>
      <p>
        <bold>BMI, BSA, and Ponderal Index (PI)</bold>
      </p>
      <p>BMI was calculated using the Quetelet equation as follows: BMI (Quetelet) = weight (kg)/length (m)<sup>2</sup>. Weight was measured using a balance scale (Filizola PL180; Filizola, Brazil) with capacity of 180 kg and an accuracy of 100 g. For height measurement, we used a vertical wall-mounted stadiometer. BMI was classified into three categories according to the World Health Organization classification for adults: underweight (&lt;18.5 kg/m<sup>2</sup>), normal weight (18.5-24.9 kg/m<sup>2</sup>), and overweight (&gt;25 kg/m<sup>2</sup>); and the Pan American Health Organization criteria for the elderly: underweight (&lt;23 kg/m<sup>2</sup>), normal weight (23-28 kg/m<sup>2</sup>), and overweight (&gt;28 kg/m<sup>2</sup>)<sup>17</sup>. In addition, we calculated BSA as weight<sup>0.5378</sup> &#215; height<sup>0.3964</sup> &#215; 0.024265 and PI as weight/height<sup>3</sup>.</p>
      <p>
        <bold>Waist circumference</bold>
      </p>
      <p>WC was measured at the midpoint between the lowest rib and the iliac crest during expiration. Patients were instructed to remain in an upright position with weight evenly distributed on both sides and breathing smoothly to prevent abdominal muscle contraction.</p>
      <p>
        <bold>Triceps Skinfold</bold>
      </p>
      <p>The TSF thickness (in mm) was obtained at the mid-point of the non-dominant arm (between the acromial process and the olecranon) with the arm freely stretched along the body. A fold of skin was then pinched with the fingers and a scientific caliper (Cescorf Scientific, Cescorf, Brazil) was applied. The measurement was repeated three times and the mean of the measurements was used for analysis. </p>
      <p>
        <bold>Arm muscle circumference</bold>
      </p>
      <p>AMC (in cm) was calculated by measuring the AC and the TSF thickness, using the following formula proposed by Jelliffe: C2 = C1-3.14*S, where C2 is the muscular circumference, C1 is the arm circumference, and S is TSF thickness (in cm)<sup>18</sup>. </p>
      <p>
        <bold>Outcome Evaluation</bold>
      </p>
      <p>Enrolled patients were followed-up at the HF and Transplant Outpatient Clinic. At the HF clinic, patients were scheduled to have regular visits at pre-defined intervals of 1-4 months. Follow-up data were directly derived from reviewing all electronic clinical data from the institutional records (most patients had several follow-up visits). For patients who were not regularly visiting the HF clinic (or were lost to follow-up), telephone contact was attempted to obtain relevant clinical events based on a structured telephone interview performed by trained nurses. For the study participants who we were unable to contact by phone (approximately 20 patients), we checked their vital status through the State Death Certificate Database, which contains data on the main cause and date of all deaths in our state. For statistical analysis we used (1) all-cause mortality and (2) HF-related hospitalizations. </p>
      <p>
        <bold>Statistical Analysis</bold>
      </p>
      <p>Baseline patient clinical characteristics were expressed as mean &#177; SD or number and percentage. Continuous variables were compared using the Student's <italic>t</italic>-test or Mann-Whitney U test as appropriate, whereas categorical variables were compared using the chi-square test or Fisher's exact test. TSF and BMI were also analyzed according to quintiles of the distribution. Survival curves were constructed using the Kaplan-Meier method and compared with the log-rank test. Cox proportional hazard regression analysis was performed to determine independent predictors of survival and included at least one anthropometric parameter (either BMI or TSF) and clinical predictors of risk [gender, age, New York Heart Association (NYHA) class, LVEF, and serum creatinine level]. A two-tailed p value &lt; 0.05 was considered statistically significant. Statistical analyses were performed using SPSS statistical software ver. 18 for Windows (SPSS, Inc., Chicago, IL, USA).</p>
      <p>
        <bold>Results</bold>
      </p>
      <p>From May 2008 to September 2009, a total of 378 HF outpatients, who were followed-up at the HF and Transplant clinic, agreed to participate in the study and had their anthropometric parameters evaluated. We excluded 34 patients from the protocol because LV function assessment indicated a LVEF &gt; 50%.</p>
      <p>Baseline clinical characteristics of the remaining study population (n = 344) are listed in <xref ref-type="table" rid="en_aop5121tab01-body2">Table 1</xref> and stratified by survival. Overall, HF patients were predominantly male, self-reportedly white, of non-ischemic etiology, in NYHA functional class I-II, and had moderate to severe LV systolic dysfunction (mean LVEF = 32 &#177; 9%). Most patients were hypertensive and 30% had diabetes. The mean follow-up period was 30.3 &#177; 8.2 months. Patients who died were older, had relatively high creatinine levels, low LVEFs, and depicted a trend towards higher NYHA functional class.</p>
      <p content-type="asset">
        <table-wrap id="en_aop5121tab01-body2">
          <graphic xlink:href="1678-4170-abc-101-05-0434-30185-gt01-en.jpg"/></table-wrap>
      </p>
      <p>Nutritional assessment parameters are listed in <xref ref-type="table" rid="en_aop5121tab02-body2">Table 2</xref>. Most HF patients were overweight when classified by BMI. There were no significant differences in most anthropometric parameters between patients who died and those who survived. In particular, mean BSA and BMI were remarkably similar in both groups, even when stratified by quintiles of the distribution. TSF was the only anthropometric index that was associated with HF prognosis. Surviving patients had a TSF 10% higher than patients who died. A TSF <underline>&gt;</underline> 20 mm was observed in only 9% of the HF patients that died during follow-up and in 22% of those that survived (p = 0.027; <xref ref-type="table" rid="en_aop5121tab02-body2">Table 2</xref>). </p>
      <p content-type="asset">
        <table-wrap id="en_aop5121tab02-body2">
          <graphic xlink:href="1678-4170-abc-101-05-0434-30185-gt02-en.jpg"/></table-wrap>
      </p>
      <p>Data regarding TSF quintiles are presented in <xref ref-type="table" rid="en_aop5121tab03-body2">Table 3</xref>. Patients within the highest TSF quintile were younger, mostly females, with lower serum creatinine levels and higher LVEFs. As expected, patients in the highest TSF quintile had higher BMIs and WCs (p &lt; 0.001). <xref ref-type="fig" rid="en_aop5121fig01-body2">Figure 1</xref> depicts HF hospitalization rates and overall mortality according to TSF quintiles. Our analysis demonstrated that HF patients within the 5<sup>th</sup> quintile had approximately a three-fold lower mortality rate than patients in the 2<sup>nd</sup>, 3<sup>rd</sup>, and 4<sup>th</sup> quintiles. No significant differences were observed in HF hospitalizations according to TSF. In addition, the Kaplan-Meier survival curves stratified by TSF progressively diverged over time (<xref ref-type="fig" rid="en_aop5121fig02-body2">Figure 2A</xref>), but such differences were not observed in the BMI-stratified analysis. </p>
      <p content-type="asset">
        <table-wrap id="en_aop5121tab03-body2">
          <graphic xlink:href="1678-4170-abc-101-05-0434-30185-gt03-en.jpg"/></table-wrap>
      </p>
      <p content-type="asset">
        <fig id="en_aop5121fig01-body2">
          <graphic xlink:href="1678-4170-abc-101-05-0434-30185-gf01-en.jpg"/></fig>
      </p>
      <p content-type="asset">
        <fig id="en_aop5121fig02-body2">
          <graphic xlink:href="1678-4170-abc-101-05-0434-30185-gf02-en.jpg"/></fig>
      </p>
      <p><xref ref-type="table" rid="tab04-body2">Table 4</xref> shows univariate analysisand multivariate Cox regression analysis results for all-cause mortality, including nutritional parameters and other clinical variables. In the univariate analysis, serum creatinine levels, LVEF, and NYHA class were associated with risk, but TSF was the single best predictor of mortality [hazard ratio (HR) = 0.36; 95% confidence interval (CI) = 0.14-0.91; p = 0.03]. Finally, after adjustment for these clinical characteristics, TSF remained a major independent predictor of overall mortality (HR = 0.36; 95% CI = 0.13-0.97). </p>
      <table-wrap id="tab04-body2">
        <graphic xlink:href="1678-4170-abc-101-05-0434-30185-gt04-en.jpg"/></table-wrap>
      <p>
        <bold>Discussion</bold>
      </p>
      <p>Despite the growing interest in the obesity paradox, there is still an ongoing debate regarding the most appropriate parameter(s) to assess the nutritional status of HF patients. Our results demonstrated that among numerous anthropometric indices (BMI, BSA, PI, TSF, WC, and AC), TSF was the only parameter that could differentiate survivors from non-survivors in a contemporary "real-world" prospective cohort of HF patients. This finding is in agreement with the concept of reverse epidemiology, as HF patients in the highest TSF quintile had lower overall mortality, even after adjustment for other important clinical predictors of risk. We did not observe a dose-response relationship between TSF and mortality, as only the superior quintile, representing a greater amount of fat mass, appeared to be an independent protective factor. In addition, unlike other studies, we did not find BMI as an adequate predictor of HF prognosis.</p>
      <p>The correlation between BMI and HF survival remains controversial. Post-hoc analysis of large clinical trials<sup>19</sup> demonstrated that lower BMI was associated with decreased survival. Symptomatic HF patients evaluated in the Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity trial with either reduced or preserved LV systolic function, underweight patients or those with a low BMI were independently associated with a substantial increased risk of death (almost 70% for BMI &lt; 22.5 kg/m<sup>2</sup>), but primarily in patients without evidence of fluid overload<sup>7</sup>. Recently, Vara et al<sup>20</sup> described this phenomenon in elderly, hospitalized, HF patients However, although obesity is frequently evaluated by BMI in clinical practice, several investigators have questioned the accuracy of BMI to assess different body composition components<sup>21-23</sup>. For instance, the relationship between BMI and body fat percentage was reportedly influenced by ethnicity and age<sup>24</sup>. In the elderly, BMI might represent a higher percentage of body fat, while in the relatively young this association is less evident<sup>25</sup>. Recently, similar to our findings, several other investigators have questioned the usefulness of BMI as a predictor of mortality or cardiac events<sup>10,14,16,26</sup>. </p>
      <p>Direct indices of body composition are theoretically the best markers to evaluate the prognostic role of nutritional status in different cardiovascular scenarios. Unfortunately, until now, there were no prospective large-scale studies that evaluated the role of these parameters on HF survival. Recently, Oreopoulos et al<sup>12</sup> evaluated the association between direct measurements of body composition by DEXA and prognostic factors in 140 chronic HF patients and demonstrated that BMI misclassified body fat status in approximately 40% of the studied patients. Also, a higher lean body mass and/or lower fat mass were independently associated with factors that are prognostically beneficial in HF, suggesting that BMI may not be a good indicator of adiposity and may, in fact, be a better surrogate for lean body mass in this population, a finding that <italic>per se</italic> might question the obesity paradox<sup>12</sup>. However, one must also consider that the association of direct body composition measurements with surrogate CVD markers may not translate into similar data regarding survival<sup>10</sup>. </p>
      <p>Anthropometry is a simple technique that is easily applied in clinical practice or in large population surveys. Numerous anthropometric parameters have been proposed to assess nutritional status and appraise different body composition components. TSF thickness measurement allows estimation of body fat content<sup>27</sup>, while limb circumferences reflect limb muscle and, thus, protein nutritional state. It is important to point out that TSF thickness measures primarily subcutaneous fat, and therefore, is insensitive to changes or abnormalities in visceral fat. Body density and body fat can be accurately estimated from the sum of TSF measurements<sup>28</sup>. Previous studies have compared and validated different body composition techniques, such as DEXA, to assess fat mass and have demonstrated an adequate accuracy to estimate body fat mass, both for subscapular and TSF thickness<sup>29</sup>. In particular, TSF has been used more frequently than other sites, because it is easy to access, reproducible, and can measure a wide range of variation among individuals<sup>30</sup>. A recent study compared body composition assessment in 118 hemodialysis patients and reported that TSF was one of the most accurate parameters to estimate total body fat percentage using DEXA as the reference test<sup>31</sup>.</p>
      <p>Lavie et al<sup>13</sup> pioneered evaluation of the prognostic role of body fat percentage based on skinfold measurements in HF patients and demonstrated that for each 1% absolute reduction in percent body fat, major clinical events increased by &gt;13%. Assessment of other anthropometric parameters, such as WC, has been proposed for HF risk stratification, but with inconsistent results<sup>14,15</sup>. Our results reinforced the concept of the obesity paradox and suggested that assessment of a simple anthropometric parameter to measure subcutaneous fat (the TSF) might be adequate to indirectly assess overall body fat mass.</p>
      <p>Regarding hospitalization risk, most reports on the assessment of the obesity paradox opted for analysis of a combined endpoint (death and hospitalization), thereby limiting separate evaluations of these events. Furthermore, some studies have found similar results, in which obesity is a predictor of only overall/cardiovascular mortality, but not hospitalization<sup>8</sup>. One possible explanation for these findings is the fact that patients with greater adiposity are diagnosed earlier with HF, which justifies why this group is younger, has less degree of cardiac dysfunction, and consequent better survival. These patients, however, may have similar vulnerability to episodes of HF decompensation than those with normal amounts of fat mass.</p>
      <p>The results of the present study should be evaluated by taking into account some methodological limitations. First, we used indirect measurements of body composition to evaluate body fat mass. Several studies, however, suggested that TSF measurement was apparently an adequate estimation of body fat<sup>27</sup>. Second, we acknowledged that anthropometry, particularly skinfold measurement, requires a considerable amount of technical skill and meticulousness. In our protocol, all parameters were evaluated by a single trained professional to avoid interobserver variability. Third, we opted to use only TSF measurements to predict body fat composition<sup>30,31</sup> instead of more complex equations based on multiple skinfolds. Although this strategy might slightly reduce the accuracy of body composition assessment, we believe that if simplifies the clinical applicability of our findings. </p>
      <p>
        <bold>Conclusion</bold>
      </p>
      <p>Our results demonstrated that TSF might be a better predictor of mortality in HF outpatients and reinforced the concept of the obesity paradox. TSF measurement has the advantages of a simple, practical, and low cost method to assess risk and can be easily implemented in clinical practice, if performed by a trained professional. </p>
      <p>
        <bold>Author contributions</bold>
      </p>
      <p>Conception and design of the research: Souza GC; Acquisition of data: Alves FD, Zuchinali P, Souza GC, Almeida KSM; Analysis and interpretation of the data: Goldraich LA, Rohde LEP, Zuchinali P; Statistical analysis: Goldraich LA, Zuchinali P; Critical revision of the manuscript for intellectual content: Clausell NO, Souza GC, Rohde LEP, Zuchinali P.</p>
      <p>
        <bold>Potential Conflict of Interest</bold>
      </p>
      <p>No potential conflict of interest relevant to this article was reported.</p>
      <p>
        <bold>Sources of Funding</bold>
      </p>
      <p>There were no external funding sources for this study.</p>
      <p>
        <bold>Study Association</bold>
      </p>
      <p>This study is not associated with any post-graduation program.</p>
      <p>
        <bold>References</bold>
      </p>
    </body>
  </sub-article>
</article>
