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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">czTDfD6CBDzNQHgHGkcpQpL</article-id>
      <article-id specific-use="scielo-v2" pub-id-type="publisher-id">S0066-782X2021000600887</article-id>
      <article-id pub-id-type="publisher-id">abc.20210074</article-id>
      <article-id pub-id-type="doi">10.36660/abc.20210074</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Minieditorial</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Obesidade, Gordura Corporal e Desfecho Cardiovascular: Al&#233;m do &#205;ndice de Massa Corporal</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="editor">
          <contrib-id contrib-id-type="orcid">0000-0001-5470-0326</contrib-id>
          <name>
            <surname>Favarato</surname>
            <given-names>Desiderio</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
          <xref ref-type="corresp" rid="c1"/>
        </contrib>
        <aff id="aff1">
          <label>1</label>
          <institution content-type="orgname">Universidade de S&#227;o Paulo</institution>
          <institution content-type="orgdiv1">Faculdade de Medicina</institution>
          <institution content-type="orgdiv2">Hospital das Clinicas</institution>
          <addr-line>
            <named-content content-type="city">S&#227;o Paulo</named-content>
            <named-content content-type="state">SP</named-content>
          </addr-line>
          <country country="BR">Brasil</country>
          <institution content-type="original">Instituto do Cora&#231;&#227;o do Hospital das Clinicas da Faculdade de Medicina da Universidade de S&#227;o Paulo, S&#227;o Paulo, SP &#8211; Brasil.</institution>
        </aff>
      </contrib-group>
      <author-notes>
        <corresp id="c1"><bold>Correspond&#234;ncia: Desiderio Favarato</bold> &#8226; Av. Dr. Eneas Carvalho de Aguiar, 40 Incor, bloco II, 2&#186; andar, sala 2. CEP <postal-code>05403-000</postal-code>, S&#227;o Paulo, SP &#8211; Brasil. E-mail: <email>desiderio.favarato@gmail.com</email></corresp>
      </author-notes>
      <pub-date publication-format="electronic" date-type="pub">
        <day>17</day>
        <month>05</month>
        <year>2021</year>
      </pub-date>
      <pub-date publication-format="electronic" date-type="collection">
        <month>05</month>
        <year>2021</year>
      </pub-date>
      <volume>116</volume>
      <issue>5</issue>
      <fpage>887</fpage>
      <lpage>888</lpage>
      <permissions>
        <license license-type="open-access" xml:lang="en" xlink:href="https://creativecommons.org/licenses/by/4.0/">
          <license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution License</license-p>
        </license>
      </permissions>
      <kwd-group xml:lang="pt">
        <title>Palavras-chave</title>
        <kwd>Obesidade</kwd>
        <kwd>Tecido Adiposo</kwd>
        <kwd>&#205;ndice de Massa Corporal</kwd>
        <kwd>Doen&#231;as Cardiovasculares</kwd>
        <kwd>Fatores de Risco</kwd>
        <kwd>Circunfer&#234;ncia Abdominal</kwd>
      </kwd-group>
      <counts>
        <fig-count count="0"/>
        <table-count count="0"/>
        <equation-count count="0"/>
        <ref-count count="6"/>
        <page-count count="2"/>
      </counts>
    </article-meta>
  </front>
  <body>
    <p>A pandemia de obesidade tem estado associada ao aumento de doen&#231;as cardiovasculares (DCV). O diagn&#243;stico de DCV &#233; feito com anteced&#234;ncia de dez anos em pessoas obesas.</p>
    <p>Embora o &#237;ndice de massa corporal (IMC) tenha sido amplamente utilizado como o principal &#237;ndice de obesidade, n&#227;o &#233; um preditor preciso de doen&#231;as cardiovasculares.</p>
    <p>Existem outras formas de medir a obesidade, desde uma simples medida da circunfer&#234;ncia abdominal (CA) at&#233; m&#233;todos mais sofisticados, como a imped&#226;ncia bioel&#233;trica e a densitometria por emiss&#227;o de raios X de dupla energia.</p>
    <p>A principal causa da imprecis&#227;o do IMC para determinar a distribui&#231;&#227;o da gordura corporal &#233; que ele pode ser normal em indiv&#237;duos com obesidade central determinada pela circunfer&#234;ncia abdominal ou com aumento da massa muscular.<xref ref-type="bibr" rid="B1"><sup>1</sup></xref></p>
    <p>Isso gerou o paradoxo da obesidade &#8212; pacientes com sobrepeso e obesos com doen&#231;a cardiovascular apresentam melhor progn&#243;stico do que aqueles com valores normais de IMC.<xref ref-type="bibr" rid="B2"><sup>2</sup></xref></p>
    <p>A discord&#226;ncia entre as duas medidas de obesidade, IMC e CA foi descrita em crian&#231;as e jovens brasileiros.<xref ref-type="bibr" rid="B3"><sup>3</sup></xref> Santos et al.,<xref ref-type="bibr" rid="B3"><sup>3</sup></xref> constataram que 5,8% dos meninos n&#227;o obesos, de acordo com o IMC, apresentavam CA acima do valor de corte, enquanto 10,6% dos meninos obesos, de acordo com o IMC, n&#227;o foram classificados como obesos se a CA fosse usada como crit&#233;rio de classifica&#231;&#227;o.<xref ref-type="bibr" rid="B3"><sup>3</sup></xref></p>
    <p>Em adultos, como mostrado em uma coorte espanhola, no estudo ENRICA,<xref ref-type="bibr" rid="B4"><sup>4</sup></xref> a preval&#234;ncia de obesidade central e CA alterada foi mais frequente do que a obesidade por IMC (36% vs. 22,9%); e nos idosos, nos quais, embora a frequ&#234;ncia de obesidade por IMC fosse semelhante entre homens e mulheres, a obesidade central mostrou-se cerca de duas vezes mais elevada em mulheres.<xref ref-type="bibr" rid="B5"><sup>5</sup></xref></p>
    <p>Quando os grupos de exposi&#231;&#227;o s&#227;o diferentes, como em estudos observacionais, &#233; necess&#225;rio um ajuste estat&#237;stico cuidadoso de fatores de confus&#227;o para obter estimativas do efeito da exposi&#231;&#227;o livre de vi&#233;s. Uma simples compara&#231;&#227;o entre as taxas de incid&#234;ncia pode ser enganosa. Portanto, abordagens computacionais mais sofisticadas foram implementadas.</p>
    <p>Quando dois grupos s&#227;o semelhantes, normalmente calculamos a influ&#234;ncia m&#233;dia do grupo, ou seja, a diferen&#231;a de frequ&#234;ncia do desfecho quando algumas caracter&#237;sticas est&#227;o presentes ou n&#227;o. No entanto, se as duas popula&#231;&#245;es estudadas forem diferentes, como em estudos observacionais e epidemiol&#243;gicos, essa compara&#231;&#227;o pode levar a resultados enganosos. Assim, por conta dessas caracter&#237;sticas diferentes ou vari&#225;veis de confus&#227;o, foram desenvolvidas abordagens computacionais por aprendizado de m&#225;quina mais sofisticadas.</p>
    <p>As vari&#225;veis de confus&#227;o podem ser analisadas como vari&#225;veis mediadoras, ou seja, embora algumas vari&#225;veis compartilhem a mesma causa, elas podem influenciar o resultado de forma diferente. Assim, o ac&#250;mulo de gordura leva &#224; obesidade central (CA aumentada) e obesidade &#8220;geral&#8221; (IMC mais elevado) com frequ&#234;ncias diferentes. Algumas pessoas podem apresentar obesidade central, mas n&#227;o apresentar IMC elevado. No entanto, o oposto &#233; incomum. Esta &#233; uma situa&#231;&#227;o em que abordagens computacionais complexas funcionam bem para revelar o efeito de cada situa&#231;&#227;o.</p>
    <p>Uma delas &#233; o algoritmo <italic>G-computation</italic>, que se baseia na estimativa do mecanismo de desfecho, da expectativa condicional do desfecho dada a exposi&#231;&#227;o (vari&#225;vel de agrupamento) e covari&#225;veis. Ou seja, qual a probabilidade do desfecho quando presentes a vari&#225;vel de exposi&#231;&#227;o e a de confus&#227;o estiver presente. Outro m&#233;todo &#233; o escore de propens&#227;o que envolve a estimativa do mecanismo de exposi&#231;&#227;o, ou seja, a probabilidade condicional de ser exposto dado um fator de confus&#227;o observado. A probabilidade de associa&#231;&#227;o em uma determinada vari&#225;vel (exposi&#231;&#227;o) quando outra (fator de confus&#227;o) est&#225; presente.</p>
    <p>A ideia subjacente ao pareamento do escore de propens&#227;o &#233; que, ao atribuir um escore de propens&#227;o a cada indiv&#237;duo do estudo, podemos comparar indiv&#237;duos em grupos de tratamento diferentes e tentar tornar os indiv&#237;duos o mais equivalentes poss&#237;vel para que possamos controlar os fatores de confus&#227;o. O resultado diferente seria apenas do tratamento. No entanto, o verdadeiro escore de propens&#227;o nunca &#233; realmente conhecido, portanto, sempre h&#225; algum n&#237;vel de incerteza em estudos observacionais.</p>
    <p>Normalmente, o escore de propens&#227;o (EP) &#233; usado como seu valor inverso denominado peso de propens&#227;o inversa. O peso para grupos ativos ou segmentados &#233; 1/EP e para grupos controle, 1/(1-EP).</p>
    <p>Outro m&#233;todo que envolve <italic>G-computation</italic> e o escore de propens&#227;o &#233; o TMLE (<italic>Targeted Maximum Likelihood Estimation</italic>), que estima tanto a expectativa condicional de um desfecho dada a exposi&#231;&#227;o e vari&#225;veis covari&#225;veis (<italic>G-computation</italic>), e a expectativa condicional de exposi&#231;&#227;o sendo determinada por uma vari&#225;vel de confus&#227;o.</p>
    <p>Nesta edi&#231;&#227;o, Saadati et al.,<xref ref-type="bibr" rid="B6"><sup>6</sup></xref> utilizam o TMLE para avaliar os efeitos totais (ET) e o efeito direto controlado da influ&#234;ncia da obesidade por IMC nos eventos cardiovasculares.</p>
    <p>Novamente, encontrou-se uma dissocia&#231;&#227;o entre as medidas de obesidade central e obesidade por IMC.</p>
    <p>O resultado final &#233; que as medidas de obesidade central s&#227;o melhores preditoras de doen&#231;as cardiovasculares pelo ac&#250;mulo de gordura do que o IMC elevado e s&#227;o respons&#225;veis por quase todos os riscos de doen&#231;as cardiovasculares do ac&#250;mulo de gordura corporal.</p>
  </body>
  <back>
    <fn-group>
      <fn fn-type="other" id="fn1">
        <p>Minieditorial referente ao artigo: O Efeito Direto do &#205;ndice de Massa Corporal nos Resultados Cardiovasculares entre Participantes sem Obesidade Central pela Estimativa por M&#225;xima Verossimilhan&#231;a Direcionada</p>
      </fn>
    </fn-group>
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  </back>
  <sub-article article-type="translation" id="S01" xml:lang="en">
    <front-stub>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Short Editorial</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Obesity, Body Fat Content and Cardiovascular Outcome: Beyond Body Mass Index</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="editor">
          <contrib-id contrib-id-type="orcid">0000-0001-5470-0326</contrib-id>
          <name>
            <surname>Favarato</surname>
            <given-names>Desiderio</given-names>
          </name>
          <xref ref-type="aff" rid="aff2">
            <sup>1</sup>
          </xref>
          <xref ref-type="corresp" rid="c2"/>
        </contrib>
        <aff id="aff2">
          <label>1</label>
          <addr-line>
            <named-content content-type="city">S&#227;o Paulo</named-content>
            <named-content content-type="state">SP</named-content>
          </addr-line>
          <country country="BR">Brazil</country>
          <institution content-type="original">Instituto do Cora&#231;&#227;o do Hospital das Clinicas da Faculdade de Medicina da Universidade de S&#227;o Paulo, S&#227;o Paulo, SP &#8211; Brazil.</institution>
        </aff>
      </contrib-group>
      <author-notes>
        <corresp id="c2"><bold>Mailing Address: Desiderio Favarato</bold> &#8226; Av. Dr. Eneas Carvalho de Aguiar, 40 Incor, bloco II, 2&#186; andar, sala 2. Postal Code <postal-code>05403-000</postal-code>, S&#227;o Paulo, SP &#8211; Brazil. E-mail: <email>desiderio.favarato@gmail.com</email></corresp>
      </author-notes>
      <kwd-group xml:lang="en">
        <title>Keywords</title>
        <kwd>Obesity</kwd>
        <kwd>Adipose Tissue</kwd>
        <kwd>Body Mass Index</kwd>
        <kwd>Cardiovascular Diseases</kwd>
        <kwd>Risk Factors</kwd>
        <kwd>Abdominal Circumference</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <p>Obesity pandemic has been associated with an increment of cardiovascular disease (CVD). Diagnosis of CVD is delivered ten years early in obese people.</p>
      <p>Although body mass index (BMI) has been widely used as the main index of obesity, it is not an accurate predictor of cardiovascular disease. There are other ways to measure obesity, varying from a simple waist circumference (WC) measurement to more sophisticated methods, like bioelectrical impedance and dual energy X-ray densitometry.</p>
      <p>The main cause of BMI inaccuracy to determine body fat distribution is that it may be normal in subjects with central obesity determined by waist circumference or high in increased muscle mass.<xref ref-type="bibr" rid="B1"><sup>1</sup></xref></p>
      <p>This has generated the obesity paradox &#8211; overweight and obese patients with cardiovascular disease present better prognosis than those with normal BMI values.<xref ref-type="bibr" rid="B2"><sup>2</sup></xref></p>
      <p>The disagreement between the two measures of obesity, BMI, and WC has been described in Brazilian children and young adults.<xref ref-type="bibr" rid="B3"><sup>3</sup></xref> Santos et al.<xref ref-type="bibr" rid="B3"><sup>3</sup></xref> found that 5.8% of non-obese boys, according to BMI, presented WC over the cut-off value, while 10.6% of obese boys, according to BMI, were not classified as obese if the WC was used as a classification criterion.<xref ref-type="bibr" rid="B3"><sup>3</sup></xref></p>
      <p>In adults, as showed in a Spanish cohort, in the ENRICA Study,<xref ref-type="bibr" rid="B4"><sup>4</sup></xref> the prevalence of central obesity and abnormal WC was more frequent than obesity by BMI (36% vs. 22.9%); and in the elderly, in whom although the frequency of BMI obesity was similar between males and female, central obesity was about twice as high in women.<xref ref-type="bibr" rid="B5"><sup>5</sup></xref></p>
      <p>When the exposure groups are dissimilar, as in observational studies, careful statistical adjustment for confounders is necessary to obtain unbiased estimates of exposure effect. A simple comparison between incidence rates may be misleading, so more sophisticated computational approaches have been implemented.</p>
      <p>If two groups are similar, we usually calculate the average group influence, that is, the difference of frequency of outcome when some characteristics are present or not. However, if the two study populations are dissimilar, such as in observational and epidemiological studies, this comparison may give misleading results. Thus, on account of these different or confounding characteristics, more sophisticated computational machine learning approaches have been developed.</p>
      <p>The confounding variables may be analyzed as a mediator variable, that is, although some variables share the same cause, they may influence the outcome differently. Thus, fat accumulation leads to central obesity (increased WC) and &#8220;general&#8221; obesity (higher BMI) with different frequencies. Some people may present central obesity but no elevated BMI. However, the opposite is unusual. This is a situation where complex computational approaches work well in revealing the effect of each one.</p>
      <p>One of them is G-computation, which relies on the estimation of the outcome mechanism, the conditional expectation of the outcome given the exposure (grouping variable) and covariates. That is, an exposure variable with other confounding variables is likely to present an outcome. Another method is the propensity score that involves estimation of the exposure mechanism, that is, the conditional probability of being exposed given an observed confounder. The probability of association in a determined variable (exposure) when another (confounder) is present.</p>
      <p>The idea underlying propensity score matching is that by giving each individual in the study a propensity score, we can compare individuals in different treatment groups and try to make the individuals as equivalent as possible so that we can control the confounding factors. The different result would be from the treatment only. However, the true propensity score is never really known, so there is always some level of uncertainty in observational studies.</p>
      <p>Usually, the propensity score (PS) is used as its inverse value named inverse propensity weight. The weight for active or targeted groups is 1/PS and for control groups, 1/(1-PS).</p>
      <p>Another method that involves both G-computation and propensity score is TMLE (Targeted Maximum Likelihood Estimation), which estimates both the conditional expectation of an outcome given the exposure and covariate variables (G-computation), and the conditional expectation of exposure being determined by a confounding variable.</p>
      <p>In this issue, Saadati et al.<xref ref-type="bibr" rid="B6"><sup>6</sup></xref> use TMLE to evaluate the total effects (TE) and the controlled direct effect of BMI obesity influence on cardiovascular events.</p>
      <p>Again, a mismatch between central obesity measures to BMI obesity was found.</p>
      <p>The final result is that central obesity measures are better predictors of cardiovascular disease from fat accumulation than high BMI, and are responsible for almost all cardiovascular disease risks.</p>
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          <p>Short Editorial related to the article: The Direct Effect of Body Mass Index on Cardiovascular Outcomes among Participants Without Central Obesity by Targeted Maximum Likelihood Estimation</p>
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