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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">tZ6BbmKqYh898w4BdQqngWH</article-id>
      <article-id pub-id-type="other">00005</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v2">S0066-782X2011000500005</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v1">S0066-782X(11)09600505</article-id>
      <article-id pub-id-type="doi">10.1590/S0066-782X2011005000039</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Artigos Originais</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Preditores de fun&#231;&#227;o ventricular esquerda global na s&#237;ndrome metab&#243;lica</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Ivanovic</surname>
            <given-names>Branislava Aleksa</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Tadic</surname>
            <given-names>Marijana Vaso</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Simic</surname>
            <given-names>Dragan Vojislav</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
      </contrib-group>
      <aff id="aff01">
        <institution content-type="orgname">Clinical Centre of Serbia</institution>
        <institution content-type="orgdiv1">Clinic for Cardiology </institution>
      </aff>
      <pub-date date-type="collection" publication-format="electronic">
        <month>05</month>
        <year>2011</year>
      </pub-date>
      <volume>96</volume>
      <issue>5</issue>
      <fpage>377</fpage>
      <lpage>385</lpage>
      <history>
        <date date-type="accepted">
          <day>03</day>
          <month>12</month>
          <year>2010</year>
        </date>
        <date date-type="rev-recd">
          <day>25</day>
          <month>10</month>
          <year>2010</year>
        </date>
        <date date-type="received">
          <day>14</day>
          <month>07</month>
          <year>2010</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 s&#237;ndrome metab&#243;lica (SM) representa um conjunto de fatores de risco cardiovascular que agem de forma sin&#233;rgica. OBJETIVO: O objetivo desse estudo foi determinar quais par&#226;metros estavam associados de forma independente &#224; fun&#231;&#227;o global do ventr&#237;culo esquerdo (VE) em indiv&#237;duos com SM, estimada atrav&#233;s do &#237;ndice Tei. M&#201;TODOS: O estudo incluiu 234 indiv&#237;duos com SM e 96 controles ajustados por idade. A SM foi definida pela presen&#231;a de tr&#234;s ou mais crit&#233;rios da ATP-NCEP III. Todos os indiv&#237;duos foram submetidos a testes laboratoriais e ecocardiograma bidimensional e com Doppler puls&#225;til e tecidual. Intervalos de tempo apropriados no Doppler tecidual para a estimativa do &#237;ndice Tei tamb&#233;m foram avaliados. RESULTADOS: O &#237;ndice Tei estava aumentado em todos os indiv&#237;duos com SM (0,35 &#177; 0,05 vs 0,49 &#177; 0,10, p &lt; 0,001). An&#225;lise de regress&#227;o m&#250;ltipla dos par&#226;metros cl&#237;nicos mostrou que a press&#227;o arterial sist&#243;lica (&#946;= 0,289, p &lt; 0,001), glicemia de jejum (&#946;= 0,205, p = 0,009), &#237;ndice de massa do VE (&#946;= 0,301, p &lt; 0,001), E/e'septal (&#946;= 0,267, p &lt; 0,001) e e'septal (&#946;= -0,176, p = 0,011) estavam independentemente associados com a fun&#231;&#227;o ventricular esquerda global estimada pelo &#237;ndice Tei. CONCLUS&#195;O: A SM teve um impacto significante na fun&#231;&#227;o global do VE. A press&#227;o arterial sist&#243;lica, glicemia de jejum, &#237;ndice de massa do VE E/e'septal, e e'septal estavam independentemente associados com a fun&#231;&#227;o global do VE.</p>
      </abstract>
      <kwd-group xml:lang="pt" kwd-group-type="author-generated">
        <kwd>Fun&#231;&#227;o ventricular esquerda</kwd>
        <kwd>sindrome metab&#243;lica</kwd>
        <kwd>isquemia mioc&#225;rdica</kwd>
        <kwd>fatores de risco</kwd>
      </kwd-group>
      <pub-date publication-format="electronic" date-type="pub">
        <day>01</day>
        <month>04</month>
        <year>2011</year>
      </pub-date>
    </article-meta>
  </front>
  <body>
    <p>
      <bold>ARTIGO ORIGINAL</bold>
    </p>
    <p>
      <bold>Preditores de fun&#231;&#227;o ventricular esquerda global na s&#237;ndrome metab&#243;lica</bold>
    </p>
    <p>
      <bold>Branislava Aleksa Ivanovic; Marijana Vaso Tadic; Dragan Vojislav Simic </bold>
    </p>
    <p>Clinic for Cardiology, Clinical Centre of Serbia</p>
    <p>
      <xref ref-type="corresp" rid="endb">Correspond&#234;ncia</xref>
    </p>
    <p>
      <bold>RESUMO</bold>
    </p>
    <p><bold>FUNDAMENTO:</bold> A s&#237;ndrome metab&#243;lica (SM) representa um conjunto de fatores de risco cardiovascular que agem de forma sin&#233;rgica. </p>
    <p><bold>OBJETIVO:</bold> O objetivo desse estudo foi determinar quais par&#226;metros estavam associados de forma independente &#224; fun&#231;&#227;o global do ventr&#237;culo esquerdo (VE) em indiv&#237;duos com SM, estimada atrav&#233;s do &#237;ndice Tei. </p>
    <p><bold>M&#201;TODOS:</bold> O estudo incluiu 234 indiv&#237;duos com SM e 96 controles ajustados por idade. A SM foi definida pela presen&#231;a de tr&#234;s ou mais crit&#233;rios da ATP-NCEP III. Todos os indiv&#237;duos foram submetidos a testes laboratoriais e ecocardiograma bidimensional e com Doppler puls&#225;til e tecidual. Intervalos de tempo apropriados no Doppler tecidual para a estimativa do &#237;ndice Tei tamb&#233;m foram avaliados. </p>
    <p><bold>RESULTADOS:</bold> O &#237;ndice Tei estava aumentado em todos os indiv&#237;duos com SM (0,35 &#177; 0,05 <italic>vs</italic> 0,49 &#177; 0,10, p &lt; 0,001). An&#225;lise de regress&#227;o m&#250;ltipla dos par&#226;metros cl&#237;nicos mostrou que a press&#227;o arterial sist&#243;lica (&#946;= 0,289, p &lt; 0,001), glicemia de jejum (&#946;= 0,205, p = 0,009), &#237;ndice de massa do VE (&#946;= 0,301, p &lt; 0,001), E/e'<sub>septal</sub> (&#946;= 0,267, p &lt; 0,001) e e'<sub>septal</sub> (&#946;= -0,176, p = 0,011) estavam independentemente associados com a fun&#231;&#227;o ventricular esquerda global estimada pelo &#237;ndice Tei. </p>
    <p><bold>CONCLUS&#195;O:</bold> A SM teve um impacto significante na fun&#231;&#227;o global do VE. A press&#227;o arterial sist&#243;lica, glicemia de jejum, &#237;ndice de massa do VE E/e'<sub>septal</sub>, e e'<sub>septal</sub> estavam independentemente associados com a fun&#231;&#227;o global do VE. </p>
    <p><bold>Palavras-chave:</bold> Fun&#231;&#227;o ventricular esquerda, sindrome metab&#243;lica, isquemia mioc&#225;rdica, fatores de risco. </p>
    <p>
      <bold>Introdu&#231;&#227;o</bold>
    </p>
    <p>O &#237;ndice de desempenho mioc&#225;rdico (&#237;ndice Tei) reflete as fun&#231;&#245;es sist&#243;lica e diast&#243;lica dos ventr&#237;culos esquerdo e direito<sup>1</sup>. Pode ser deficiente em pacientes com v&#225;rios fatores de risco, tais como hipertens&#227;o<sup>2</sup>, diabete<sup>3</sup> e obesidade<sup>4</sup>. A influ&#234;ncia da s&#237;ndrome metab&#243;lica (SM) na fun&#231;&#227;o global do ventr&#237;culo esquerdo (VE) ainda n&#227;o foi determinada de forma completa. H&#225; diferentes opini&#245;es sobre esse problema; por um lado h&#225; autores que acreditam que a SM &#233; um conjunto de fatores de risco e, sendo assim, a altera&#231;&#227;o na fun&#231;&#227;o global do VE &#233; uma consequ&#234;ncia esperada e l&#243;gica<sup>5,6</sup>. Por outro lado, alguns investigadores mostraram que o &#237;ndice Tei n&#227;o est&#225; alterado de forma significativa em pacientes com alta preval&#234;ncia de obesidade, hipertens&#227;o e diabete, os quais s&#227;o fatores de risco importantes da s&#237;ndrome metab&#243;lica<sup>7</sup>. Poucos estudos analisaram o impacto dos fatores de risco individuais da SM na fun&#231;&#227;o global do VE. </p>
    <p>O objetivo do presente estudo foi determinar quais par&#226;metros cl&#237;nicos e ecocardiogr&#225;ficos se correlacionam com a fun&#231;&#227;o global do VE em pacientes com SM e tamb&#233;m identificar quais par&#226;metros estavam associados de forma independente com o &#237;ndice Tei. </p>
    <p>
      <bold>Metodologia</bold>
    </p>
    <p>A investiga&#231;&#227;o incluiu 330 indiv&#237;duos divididos em dois grupos: o primeiro grupo consistia em 234 indiv&#237;duos (125 mulheres e 109 homens) com SM, enquanto o grupo controle consistia em 96 indiv&#237;duos (52 mulheres e 44 homens) sem fatores de risco de SM. Pacientes com sinais cl&#237;nicos ou laboratoriais de insufici&#234;ncia card&#237;aca, doen&#231;a arterial coronariana, les&#227;o cerebrovascular anterior, doen&#231;a valvar card&#237;aca, hipertens&#227;o secund&#225;ria ou outras doen&#231;as cr&#244;nicas tais como cirrose hep&#225;tica, insufici&#234;ncia renal ou doen&#231;as endocrinol&#243;gicas (exceto diabete melito tipo 2) foram exclu&#237;dos do estudo. SM foi definida pela presen&#231;a de tr&#234;s ou mais crit&#233;rios do <italic>Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III - NCEP-ATP-III)</italic> de 2001<sup>8</sup>: obesidade abdominal (circunfer&#234;ncia da cintura <underline>&gt;</underline> 102 cm em homens e <underline>&gt;</underline> 88 cm em mulheres), triglic&#233;rides de jejum <underline>&gt;</underline> 150 mg/dl, n&#237;veis diminu&#237;dos de HDL colesterol (&lt;40mg/dl em homens e &lt; 50 mg/dl em mulheres), press&#227;o arterial elevada (<underline>&gt;</underline> 130/85 mmHg ou terapia anti-hipertensiva) e glicemia de jejum <underline>&gt;</underline> 110 mg/dl. </p>
    <p>As medidas antropom&#233;tricas (altura, peso, circunfer&#234;ncia da cintura) foram obtidas de todos os indiv&#237;duos inclu&#237;dos no estudo a fim de calcular a &#225;rea de superf&#237;cie corporal (ASC) e &#237;ndice de massa corporal (IMC). Em rela&#231;&#227;o &#224; an&#225;lise laboratorial, utilizamos os n&#237;veis de glicemia de jejum, hemoglobina glicosilada, colesterol total e lipoprote&#237;na de alta e baixa densidade colesterol (HDL e LDL, respectivamente), triglic&#233;rides, &#225;cido &#250;rico e creatinina s&#233;rica. </p>
    <p>Os valores da press&#227;o arterial (PA) foram obtidos atrav&#233;s da medida do valor m&#233;dio de duas medi&#231;&#245;es consecutivas na posi&#231;&#227;o sentada com um intervalo de cinco minutos, pela manh&#227;, utilizando um esfigmoman&#244;metro convencional. </p>
    <p>O diagn&#243;stico de diabete foi baseado nos crit&#233;rios da Organiza&#231;&#227;o Mundial da Sa&#250;de (OMS) publicados em 2006<sup>9</sup> e hipertens&#227;o arterial foi estabelecida de acordo com as recomenda&#231;&#245;es da <italic>European Association for Hypertension </italic>em 2007<sup>10</sup>. O protocolo foi aprovado pelo Comit&#234; de &#201;tica da Faculdade de Medicina da Universidade de Belgrado. Consentimento informado foi obtido de todos os participantes. </p>
    <p>
      <bold>Ecocardiografia</bold>
    </p>
    <p>O exame ecocardiogr&#225;fico foi realizado com o ecocardiografo Acuson Sequoia 256 com um transdutor de 2 a 4 MHz. Os valores de todos os par&#226;metros ecocardiogr&#225;ficos foram obtidos como o valor m&#233;dio de cinco ciclos card&#237;acos consecutivos. O di&#226;metro sist&#243;lico final do VE (DSFVE) e o di&#226;metro diast&#243;lico final do VE (DDFVE), a espessura da parede posterior (EPP) do VE e a do septo interventricular (ESI) foram determinados de acordo com as recomenda&#231;&#245;es da <italic>American Society of Echocardiography</italic><sup>11</sup>. Os volumes finais sist&#243;lico e diast&#243;lico do VE e par&#226;metros da fun&#231;&#227;o sist&#243;lica (fra&#231;&#227;o de eje&#231;&#227;o - FE e encurtamento fracional - EF) foram estimados pela f&#243;rmula de Teichholz. A espessura relativa da parede (ERP) foi calculada como (2x PWT)/DDFVE. </p>
    <p>A massa ventricular esquerda (MVE) foi calculada atrav&#233;s da f&#243;rmula de Penn: MVE = 1.04x[(DDFVE + EPPD + ESI)<sup>3</sup> - (DDFVE)<sup>3</sup> - 13,6 g<sup>12</sup>. O &#237;ndice de massa do VE (massa do VE/Alt<sup>2,7</sup>) foi calculado como a raz&#227;o entre a massa ventricular esquerda e a altura<sup>2,7</sup>. Hipertrofia ventricular esquerda foi definida como massa VE/Alt<sup>2,7</sup><underline>&gt;</underline> 51 g/m<sup>2,7</sup> para homens e <underline>&gt;</underline> 49,5 g/m<sup>2,7</sup> para mulheres<sup>13</sup>. </p>
    <p>A an&#225;lise das velocidades de fluxo transmitral foi obtida por Doppler puls&#225;til no corte apical quatro c&#226;maras com o volume da amostra posicionado na borda dos folhetos da valva mitral<sup>14</sup>. As medidas inclu&#237;ram as velocidades diast&#243;lica inicial transmitral (onda E) e atrial (onda A) para calcular a raz&#227;o E/A e o tempo de desacelera&#231;&#227;o (TD) da onda E<sup>13</sup>. A imagem do Doppler tecidual foi utilizada para obter as velocidades mioc&#225;rdicas do VE no corte apical quatro c&#226;maras com volume de amostra de 2 mm posicionado no segmento septal do anel mitral durante a di&#225;stole inicial (e&#180;<sub>septal</sub>) e s&#237;stole (s<sub>septal</sub>)<sup>14</sup>. A raz&#227;o E/e&#180;<sub>septal</sub> foi determinada atrav&#233;s de valores previamente estimados de velocidades de fluxo E e e'<sub>septal</sub> na di&#225;stole inicial obtidas por Doppler tecidual e puls&#225;til. </p>
    <p>Os par&#226;metros necess&#225;rios para calcular o &#237;ndice Tei foram obtidos atrav&#233;s de Doppler tecidual no corte apical de quatro c&#226;maras<sup>15</sup>. Um volume de amostra de 2 mm foi posicionado no canto lateral do anel mitral. O tempo de contra&#231;&#227;o isovolum&#233;trica (TCIV) e o tempo de relaxamento isovolum&#233;trico (TRIV) foram medidos do final do padr&#227;o de velocidade do anel mitral at&#233; o in&#237;cio da onda S e do final da onda S at&#233; o in&#237;cio do padr&#227;o de velocidade do anel mitral, respectivamente. </p>
    <p>O tempo de eje&#231;&#227;o (TE) foi definido como a dura&#231;&#227;o do fluxo de sa&#237;da do VE no perfil de velocidade do Doppler. </p>
    <p>O &#237;ndice Tei foi calculado de acordo com a f&#243;rmula: &#205;ndice Tei = (TCIV + TRIV)/TE<sup>1</sup>. </p>
    <p>
      <bold>An&#225;lises estat&#237;sticas</bold>
    </p>
    <p>Vari&#225;veis cont&#237;nuas foram apresentadas como m&#233;dias &#177; desvios-padr&#227;o (DP) e comparadas atrav&#233;s de teste <italic>t</italic> para duas amostras independentes, considerando que apresentavam distribui&#231;&#227;o normal. Diferen&#231;as entre propor&#231;&#245;es foram comparadas usando teste &#967;<sup>2</sup>. O coeficiente de correla&#231;&#227;o de Pearson foi utilizado para determinar a correla&#231;&#227;o entre o &#237;ndice Tei e a diferentes par&#226;metros cl&#237;nicos e ecocardiogr&#225;ficos. O mesmo teste foi usado para determinar a correla&#231;&#227;o entre esses par&#226;metros e intervalos do Doppler tecidual que eram necess&#225;rios para o c&#225;lculo do &#237;ndice Tei (TRIV, TCIV e TE). A an&#225;lise de regress&#227;o m&#250;ltipla <italic>stepwise</italic> determinou quais par&#226;metros, cl&#237;nicos e ecocardiogr&#225;ficos, estavam associados de forma independente com o &#237;ndice Tei ou seus componentes (TRIV, TCIV e TE). A frequ&#234;ncia card&#237;aca (FC) e a vari&#225;vel cujo valor de <italic>p</italic> era <underline>&lt;</underline> 0.10 foram inclu&#237;das nos modelos de regress&#227;o <italic>stepwise</italic>. Tamb&#233;m determinamos quais componentes da SM se correlacionavam e quais componentes estavam independentemente associados com o &#237;ndice Tei. Um valor de p &lt; 0,05 foi considerado estatisticamente significante. </p>
    <p>
      <bold>Resultados</bold>
    </p>
    <p>N&#227;o havia diferen&#231;a estatisticamente significante na m&#233;dia da idade entre os indiv&#237;duos com SM e os controles (52 &#177; 9 <italic>vs</italic> 54 &#177; 9 anos, p &gt; 0,05). Todos os par&#226;metros cl&#237;nicos do grupo de estudo s&#227;o mostrados na <xref ref-type="table" rid="tab1">Tabela 1</xref>. Os valores de todos os par&#226;metros da SM eram significantemente mais altos nos pacientes com SM do que nos controles (<xref ref-type="table" rid="tab1">Tabela 1</xref>). Tamb&#233;m observamos que os n&#237;veis de hemoglobina glicosilada, acido &#250;rico, creatinina s&#233;rica, LDL-colesterol e colesterol total eram significantemente mais altos na popula&#231;&#227;o de pacientes com SM (<xref ref-type="table" rid="tab1">Tabela 1</xref>).</p>
    <table-wrap id="tab1">
      <graphic xlink:href="1678-4170-abc-96-05-0377-00039-gt01.jpg"/></table-wrap>
    <p>N&#227;o havia diferen&#231;a estatisticamente significante entre os grupos estudados em rela&#231;&#227;o &#224; di&#226;metro do VE, FE e EF (<xref ref-type="table" rid="tab2">Tabela 2</xref>). A espessura relativa da parede e o &#237;ndice de massa do VE estavam significantemente aumentados no grupo com SM (<xref ref-type="table" rid="tab2">Tabela 2</xref>). Comparado ao grupo controle, o grupo SM apresentava uma porcentagem significantemente maior de hipertrofia do VE (<xref ref-type="table" rid="tab2">Tabela 2</xref>). </p>
    <table-wrap id="tab2">
      <graphic xlink:href="1678-4170-abc-96-05-0377-00039-gt02.jpg"/></table-wrap>
    <p>O par&#226;metro da fun&#231;&#227;o sist&#243;lica obtido atrav&#233;s de Doppler tecidual (s<sub>septal</sub>) demonstrou fun&#231;&#227;o sist&#243;lica do VE normal em indiv&#237;duos com SM. Entretanto, os par&#226;metros da fun&#231;&#227;o diast&#243;lica do VE, como E/A, TD, e'<sub>septal</sub> e E/e'<sub>septal</sub> apresentavam-se significantemente deteriorados no grupo com SM (<xref ref-type="table" rid="tab2">Tabela 2</xref>). </p>
    <p>Os par&#226;metros necess&#225;rios para o c&#225;lculo do &#237;ndice Tei tamb&#233;m estavam alterados em indiv&#237;duos com SM. O TRIV e TCIV apresentavam-se significantemente prolongados, enquanto o TE estava encurtado no grupo SM, o que determinava o valor aumentado do &#237;ndice Tei (<xref ref-type="table" rid="tab2">Tabela 2</xref>). </p>
    <p>An&#225;lises de correla&#231;&#227;o univariada mostraram que FC, press&#227;o arterial sist&#243;lica (PAS), press&#227;o arterial diast&#243;lica (PAD), n&#237;veis de glicose, triglic&#233;rides, colesterol total e creatinina s&#233;rica e valores de circunfer&#234;ncia da cintura (CC) estavam associados com a fun&#231;&#227;o global do VE estimada pelo &#237;ndice Tei (<xref ref-type="table" rid="tab3">Tabela 3</xref>). Entre os par&#226;metros ecocardiogr&#225;ficos, as an&#225;lises de correla&#231;&#227;o univariada demonstraram que a espessura relativa da parede, di&#226;metro atrial esquerdo, &#237;ndice de massa do VE, raz&#227;o E/A, s<sub>septal</sub>, e'<sub>septal</sub> e raz&#227;o E/e'<sub>septal</sub> se correlacionavam com o &#237;ndice de desempenho mioc&#225;rdico do VE (<xref ref-type="table" rid="tab3">Tabela 3</xref>). A an&#225;lise de regress&#227;o m&#250;ltipla dos par&#226;metros cl&#237;nicos e ecocardiogr&#225;ficos demonstrou que a PAS, n&#237;vel de glicose, &#237;ndice de massa do VE, e'<sub>septal</sub> e raz&#227;o E/e'<sub>septal</sub> estavam associados de forma independente com a fun&#231;&#227;o global do VE estimada atrav&#233;s do &#237;ndice Tei (<xref ref-type="table" rid="tab4">Tabela 4</xref>). </p>
    <table-wrap id="tab3">
      <graphic xlink:href="1678-4170-abc-96-05-0377-00039-gt03.jpg"/></table-wrap>
    <table-wrap id="tab4">
      <graphic xlink:href="1678-4170-abc-96-05-0377-00039-gt04.jpg"/></table-wrap>
    <p>Al&#233;m disso, determinamos quais par&#226;metros estavam associados com todos os intervalos de tempo usados na equa&#231;&#227;o do &#237;ndice Tei (TRIV, TCIV e TE). </p>
    <p>A an&#225;lise univariada dos par&#226;metros cl&#237;nicos e ecocardiogr&#225;ficos no grupo SM mostrou que a PAS, n&#237;veis de glicemia de jejum, CC, espessura relativa da parede, di&#226;metro atrial esquerdo, &#237;ndice de massa do VE, raz&#227;o E/A, tempo de desacelera&#231;&#227;o (TD), e'<sub>septal</sub> e raz&#227;o E/e'<sub>septal</sub> estavam associados com o TRIV (<xref ref-type="table" rid="aop03011tab05m">Tabela 5</xref>). Al&#233;m disso, todos esses par&#226;metros, exceto o di&#226;metro atrial esquerdo, raz&#227;o E/A e TD, estavam independentemente associados com o TRIV (<xref ref-type="table" rid="aop03011tab06m">Tabela 6</xref>). </p>
    <p content-type="asset">
      <table-wrap id="aop03011tab05m">
        <graphic xlink:href="1678-4170-abc-96-05-0377-00039-gt05.jpg"/></table-wrap>
    </p>
    <p content-type="asset">
      <table-wrap id="aop03011tab06m">
        <graphic xlink:href="1678-4170-abc-96-05-0377-00039-gt06.jpg"/></table-wrap>
    </p>
    <p>A an&#225;lise de correla&#231;&#227;o mostrou que a PAS, PAD, n&#237;veis de glicemia de jejum, CC, espessura relativa da parede, di&#226;metro atrial esquerdo, &#237;ndice de massa do VE, raz&#227;o E/A, TD, e'<sub>septal</sub> e raz&#227;o E/e'<sub>septal</sub> estavam associados com o TCIV (<xref ref-type="table" rid="aop03011tab05m">Tabela 5</xref>). Todos os par&#226;metros mencionados, exceto a PAD, estavam associados de forma independente com o TCIV (<xref ref-type="table" rid="aop03011tab06m">Tabela 6</xref>). </p>
    <p>A an&#225;lise univariada tamb&#233;m demonstrou que a PAS, di&#226;metro atrial esquerdo, &#237;ndice de massa do VE, FE, s<sub>septal</sub>, TD, e'<sub>septal</sub> e raz&#227;o E/e'<sub>septal</sub> estavam associados com o TE (<xref ref-type="table" rid="aop03011tab05m">Tabela 5</xref>). Entretanto, apenas a PAS, &#237;ndice de massa do VE, FE e s<sub>septal</sub> estavam associados de forma independente com o TE (<xref ref-type="table" rid="aop03011tab06m">Tabela 6</xref>). </p>
    <p>A an&#225;lise de correla&#231;&#227;o mostrou que todos os componentes da SM, exceto o HDL-colesterol, estavam associados com o &#237;ndice Tei, mas apenas a PAS, n&#237;veis de glicemia de jejum e triglic&#233;rides estavam associados de forma independente com esse par&#226;metro da fun&#231;&#227;o global do VE (<xref ref-type="table" rid="tab7">Tabela 7</xref>). </p>
    <table-wrap id="tab7">
      <graphic xlink:href="1678-4170-abc-96-05-0377-00039-gt07.jpg"/></table-wrap>
    <p>
      <bold>Discuss&#227;o </bold>
    </p>
    <p>O &#237;ndice Tei &#233; um par&#226;metro ecocardiogr&#225;fico especial que simultaneamente mostra as fun&#231;&#245;es sist&#243;lica e diast&#243;lica de um ventr&#237;culo. </p>
    <p>N&#227;o h&#225; um consenso sobre o impacto da idade e FC no &#237;ndice Tei<sup>2,3,5,7,16</sup>. Nosso estudo mostrou que o &#237;ndice da fun&#231;&#227;o global do VE era independente da idade, o que &#233; muito importante para a avalia&#231;&#227;o da fun&#231;&#227;o global do VE em pacientes de diferentes idades. Por outro lado, esse estudo mostrou que a FC se correlacionava com o &#237;ndice Tei, embora n&#227;o de forma independente. Resultados similares foram obtidos em outros estudos<sup>2,17</sup>. </p>
    <p>A hipertens&#227;o arterial altera a estrutura mioc&#225;rdica, primariamente devido ao ac&#250;mulo anormal de col&#225;geno no espa&#231;o extracelular, resultando em uma diminui&#231;&#227;o da complac&#234;ncia e aparecimento de disfun&#231;&#227;o diast&#243;lica do VE<sup>18</sup>. </p>
    <p>N&#227;o h&#225; um consenso universal sobre a influ&#234;ncia da PAS e da PAD na fun&#231;&#227;o ventricular global do VE e o &#237;ndice Tei. Alguns autores mostraram que o &#237;ndice Tei se correlaciona com a press&#227;o arterial<sup>5,15,19</sup>, enquanto outros discordam<sup>2,17</sup>. Nosso estudo mostrou que a PAS e a PAD se correlacionaram com o &#237;ndice de desempenho mioc&#225;rdico, mas apenas a PAS estava associada de forma independente com o &#237;ndice Tei. O mesmo resultado foi obtido quando consideramos apenas os crit&#233;rios da SM. Al&#233;m disso, a PAS mostrou ser o preditor independente mais forte do &#237;ndice Tei entre os crit&#233;rios da SM com maior signific&#226;ncia estat&#237;stica (p &lt; 0,001). </p>
    <p>A resist&#234;ncia &#224; insulina subjacente &#224; diabete melito tipo 2 e SM leva &#224; altera&#231;&#245;es significantes na estrutura e fun&#231;&#227;o do VE. Basicamente, ela leva &#224; ativa&#231;&#227;o do sistema nervoso simp&#225;tico e do sistema renina-angiotensina-aldosterona (SRAA), causando redu&#231;&#227;o no n&#250;mero de mitoc&#244;ndrias, elementos contr&#225;teis, densidade da rede capilar, e induz fibrose extracelular e apoptose<sup>20</sup>. Todas essas altera&#231;&#245;es resultam no aparecimento de disfun&#231;&#227;o diast&#243;lica do VE e, subsequentemente, hipertrofia do VE. Pattoneri e cols. <sup>3</sup> mostraram que indiv&#237;duos recentemente diagnosticados com diabete melito tipo 2 apresentavam fun&#231;&#227;o global do VE anormal. H&#225; um dilema em rela&#231;&#227;o a se os n&#237;veis de glicose e hemoglobina glicada afetam ou n&#227;o a fun&#231;&#227;o global do VE. Estudos tem confirmado que essa rela&#231;&#227;o existe<sup>3,5,19</sup>, o que tamb&#233;m foi o resultado de nosso estudo. A an&#225;lise separada da influ&#234;ncia dos componentes da SM em nosso estudo tamb&#233;m demonstrou que os n&#237;veis de glicemia de jejum, al&#233;m da PAS e n&#237;veis de triglic&#233;rides, estavam associados de forma independente com o &#237;ndice Tei. </p>
    <p>Os estudos que investigaram os efeitos individuais e simult&#226;neos da hipertens&#227;o e diabete na fun&#231;&#227;o global do VE n&#227;o chegaram a um acordo sobre se esses fatores sinergisticamente levam &#224; maior dano no VE. Cho e cols. <sup>21</sup> mostraram que os efeitos simult&#226;neos desses fatores alteravam a fun&#231;&#227;o global do VE mais do que os fatores individuais separadamente. Outros autores discordam e acreditam que as diferen&#231;as entre os efeitos individuais e simult&#226;neos desses dois fatores n&#227;o existem<sup>3,17</sup>. </p>
    <p>N&#227;o h&#225; consenso absoluto sobre o impacto da obesidade no &#237;ndice Tei. Levent e cols. <sup>4</sup> estudaram o efeito da hipertens&#227;o e obesidade em crian&#231;as e mostrou que crian&#231;as obesas, mas normotensas, tinham um &#237;ndice Tei mais alto, quando comparadas ao grupo controle, o que confirmava dano &#224; fun&#231;&#227;o global do VE, enquanto crian&#231;as com ambos os fatores de risco apresentavam um n&#237;vel ainda maior de disfun&#231;&#227;o, o que indicava um poss&#237;vel efeito sinerg&#237;stico desses fatores. O estudo em uma popula&#231;&#227;o adulta confirmou que a obesidade prejudicava a fun&#231;&#227;o mioc&#225;rdica global pela diminui&#231;&#227;o do &#237;ndice Tei, isto &#233;, mostrando a melhora na fun&#231;&#227;o mioc&#225;rdica com a redu&#231;&#227;o do peso<sup>22</sup>. H&#225; um estudo controverso que mostrou que a obesidade n&#227;o piorava, mas sim melhorava a fun&#231;&#227;o global do VE<sup>23</sup>. Entretanto, os autores n&#227;o sugeriram poss&#237;veis mecanismos para esse efeito "protetor" do aumento do peso corporal. Nosso estudo mostrou que o IMC n&#227;o se correlacionava com &#237;ndice Tei, em contraste com a CC, que era um preditor independente da fun&#231;&#227;o global do VE. Esses achados eram esperados, pois n&#227;o havia diferen&#231;a significante no IMC entre os grupos SM e controle, enquanto a CC era significantemente maior nos indiv&#237;duos com SM. Voulgari e cols. <sup>19</sup> obtiveram resultados similares. </p>
    <p>Nesse estudo, mostramos que os n&#237;veis de LDL e HDL-colesterol n&#227;o se correlacionavam com o &#237;ndice Tei, enquanto os n&#237;veis de colesterol total e triglic&#233;rides se correlacionavam com esse par&#226;metro. Os n&#237;veis de triglic&#233;rides n&#227;o se associavam de forma independente com o &#237;ndice Tei, quando todos os par&#226;metros cl&#237;nicos e ecocardiogr&#225;ficos eram considerados. Entretanto, quando somente os crit&#233;rios da SM eram considerados, os n&#237;veis de triglic&#233;rides associavam-se de forma independente com esse &#237;ndice, o que est&#225; de acordo com os achados de outros autores<sup>5,19</sup>. de las Fuentes e cols. <sup>24</sup> foram os primeiros a mostrar que indiv&#237;duos com n&#237;veis de triglic&#233;rides (TG) aumentados apresentavam fun&#231;&#227;o diast&#243;lica do VE significantemente deficiente e aumento da massa do VE, quando comparados ao grupo controle. Isso pode ser explicado pelo fato de que os TG acumulados no espa&#231;o extracelular reduzem a complac&#234;ncia do VE, tendo como consequ&#234;ncia seus efeitos lipot&#243;xicos nos cardiomi&#243;citos e alto consumo de energia, que &#233; necess&#225;rio para seu metabolismo. </p>
    <p>Nosso estudo tamb&#233;m mostrou que a fun&#231;&#227;o renal estimada atrav&#233;s da creatinina s&#233;rica estava elevada em indiv&#237;duos com SM e se correlacionava com o &#237;ndice Tei, o que est&#225; de acordo com alguns autores<sup>25</sup>, mas contradit&#243;rio para outros<sup>26</sup>. Entretanto, a creatinina s&#233;rica n&#227;o estava associada de forma independente com o &#237;ndice Tei. </p>
    <p>A rela&#231;&#227;o entre v&#225;rios par&#226;metros ecocardiogr&#225;ficos e o &#237;ndice Tei foi avaliada em pacientes com hipertens&#227;o, diabete ou aqueles que apresentavam ambos os fatores de risco<sup>2,3,17</sup>; entretanto, essa avalia&#231;&#227;o n&#227;o havia ainda sido realizada em indiv&#237;duos com SM. A maioria dos autores acredita que a fun&#231;&#227;o global do VE deficiente na SM &#233; na verdade uma consequ&#234;ncia do dano &#224; fun&#231;&#227;o diast&#243;lica<sup>5,6,19</sup>, que &#233;, em sua maior parte, o resultado da identifica&#231;&#227;o da fun&#231;&#227;o sist&#243;lica do VE realizada apenas com a fra&#231;&#227;o de eje&#231;&#227;o sist&#243;lica e/ou o encurtamento fracional do VE. Entretanto, h&#225; estudos mostrando que esses par&#226;metros tamb&#233;m poderiam estar alterados em indiv&#237;duos com SM<sup>26</sup>. O estudo de imagem por Doppler tecidual introduziu novos par&#226;metros da fun&#231;&#227;o sist&#243;lica do VE, que mostrou estar deficiente no grupo com SM<sup>27</sup>. Nosso estudo mostrou que a fun&#231;&#227;o sist&#243;lica do VE estimada atrav&#233;s da FE e s<sub>septal</sub> estava preservada no grupo com SM, embora com signific&#226;ncia estat&#237;stica lim&#237;trofe. </p>
    <p>Todos os par&#226;metros da fun&#231;&#227;o diast&#243;lica do VE avaliados em nosso estudo (E/A, TD, e'<sub>septal</sub> e raz&#227;o E/e'<sub>septal</sub>) confirmaram a exist&#234;ncia de disfun&#231;&#227;o diast&#243;lica. A espessura relativa da parede e o &#237;ndice de massa do VE, o di&#226;metro atrial esquerdo, a raz&#227;o E/A, s<sub>septal</sub>, e'<sub>septal</sub> e a raz&#227;o E/e'<sub> septal</sub> se correlacionaram com a fun&#231;&#227;o global do VE estimada atrav&#233;s do &#237;ndice Tei; entretanto, o &#237;ndice de massa do VE, e'<sub>septal</sub> e raz&#227;o E/e'<sub>septal</sub> estavam associados de forma independente com o &#237;ndice Tei. Resultados similares foram obtidos por Masugata e cols. <sup>2</sup> em pacientes com hipertens&#227;o. Andersen e cols. <sup>17</sup> descobriram uma correla&#231;&#227;o entre o &#237;ndice Tei e o TD e a raz&#227;o E/A ratio em pacientes com hipertens&#227;o e diabete, enquanto Pattoneri e cols. <sup>3</sup> encontraram uma correla&#231;&#227;o entre o TCIV e o TE com esse &#237;ndice em pacientes com diabete de diagn&#243;stico recente. </p>
    <p>Al&#233;m disso, estudamos o impacto de diferentes par&#226;metros cl&#237;nicos e ecocardiogr&#225;ficos no grupo SM sobre os intervalos do Doppler tecidual necess&#225;rios para o c&#225;lculo do &#237;ndice Tei (TRIV, TCIV e TE). A PAS, glicemia de jejum, CC, espessura relativa da parede, &#237;ndice de massa do VE, e'<sub>septal</sub> e raz&#227;o E/e'<sub>septal</sub> estavam associados de forma independente com o TRIV. A an&#225;lise multivariada mostrou que a PAS, PAD, glicemia de jejum, &#237;ndice de massa do VE, e'<sub>septal</sub> e raz&#227;o E/e'<sub>septal</sub> estavam associados de forma independente com o TCIV. Esses par&#226;metros representam, simultaneamente, as fun&#231;&#245;es sist&#243;lica e diast&#243;lica do VE na equa&#231;&#227;o do &#237;ndice de Tei. Por outro lado, o TE, um par&#226;metro da fun&#231;&#227;o sist&#243;lica nessa equa&#231;&#227;o, estava associado de forma independente com a PAS, &#237;ndice de massa do VE, FE e s<sub>septal</sub>. Aparentemente, quase os mesmos fatores que est&#227;o associados com TRIV, TCIV e TE na SM se correlacionaram com o &#237;ndice Tei como par&#226;metro da fun&#231;&#227;o global do VE. Esses achados s&#227;o importantes, pois demonstramos que n&#227;o &#233; necess&#225;rio determinar fatores de risco para componentes individuais do &#237;ndice Tei. </p>
    <p>Considerando que a fun&#231;&#227;o sist&#243;lica do VE estava preservada em indiv&#237;duos com SM em nosso estudo, enquanto, por outro lado, a fun&#231;&#227;o diast&#243;lica estava deficiente, a conclus&#227;o l&#243;gica &#233; que o dano &#224; fun&#231;&#227;o global do VE &#233; na verdade o resultado de altera&#231;&#245;es na fun&#231;&#227;o diast&#243;lica. Entretanto, um grupo de estudo maior possivelmente teria demonstrado que a fun&#231;&#227;o sist&#243;lica do VE tamb&#233;m estava alterada em indiv&#237;duos com SM, considerando que o valor estat&#237;stico em nosso estudo foi lim&#237;trofe (p=0,075). </p>
    <p>A limita&#231;&#227;o do presente estudo consistiu em um grande n&#250;mero de indiv&#237;duos com SM e hipertens&#227;o arterial, que era controlada atrav&#233;s do uso de diferentes medicamentos que poderiam afetar o &#237;ndice Tei e a interpreta&#231;&#227;o dos resultados. Outra limita&#231;&#227;o &#233; o fato de que poucos estudos cl&#237;nicos utilizaram a imagem do Doppler tecidual para obter par&#226;metros de fun&#231;&#227;o sist&#243;lica, diast&#243;lica e global do VE; sendo assim, n&#227;o pudemos realizar uma compara&#231;&#227;o completa desses par&#226;metros. Estudos diagn&#243;sticos demonstraram que o &#237;ndice Tei obtido por Doppler puls&#225;til e tecidual apresentavam valores similares e embora tenha sido demonstrado que os valores determinados pelo Doppler tecidual s&#227;o mais precisos e apresentam melhor correla&#231;&#227;o com as medidas invasivas obtidas durante a cateteriza&#231;&#227;o card&#237;aca, a compara&#231;&#227;o &#233; bastante razo&#225;vel<sup>28</sup>. A terceira limita&#231;&#227;o &#233; relativa &#224; depend&#234;ncia da pr&#233;-carga que o &#237;ndice Tei apresenta<sup>29</sup>. </p>
    <p>
      <bold>Conclus&#227;o</bold>
    </p>
    <p>A s&#237;ndrome metab&#243;lica leva &#224; dano card&#237;aco subcl&#237;nico, reduzindo a fun&#231;&#227;o global do VE. O &#237;ndice Tei &#233; uma maneira relativamente simples de estimar a fun&#231;&#227;o global do VE e portanto, um par&#226;metro valioso na pr&#225;tica cl&#237;nica rotineira. A an&#225;lise de regress&#227;o m&#250;ltipla dos par&#226;metros cl&#237;nicos mostrou que a PAS, glicemia de jejum, &#237;ndice de massa do VE, raz&#227;o E/e'<sub>septal</sub>, e e'<sub>septal</sub> estavam associados de forma independente com a fun&#231;&#227;o global do VE estimada atrav&#233;s do &#237;ndice Tei. Tamb&#233;m demonstramos que quase os mesmos fatores que est&#227;o associados com o TRIV, TCIV e TE no grupo com SM tamb&#233;m est&#227;o associados com o &#237;ndice Tei. A fun&#231;&#227;o diast&#243;lica deficiente do VE &#233; a principal raz&#227;o para a deteriora&#231;&#227;o da fun&#231;&#227;o global do VE na SM, de acordo com nosso estudo. </p>
    <p>Al&#233;m disso, mostramos que, entre os componentes da SM, apenas a press&#227;o arterial sist&#243;lica, glicemia de jejum e n&#237;veis de triglic&#233;rides estavam associados de forma independente com a fun&#231;&#227;o global do ventr&#237;culo esquerdo. </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="endb" fn-type="corresp">
        <label>
          <bold>Correspond&#234;ncia:</bold>
        </label>
        <p> Branislava Aleksa Ivanovic </p>
        <p> Bul.Mihaila Pupina 151 - 11070 Novi Beograd </p>
        <p> 11000 - Belgrade - Serbia </p>
        <p> E-mail: </p>
        <p>
          <email xlink:href="lole@scnet.rs">lole@scnet.rs</email>
        </p>
      </fn>
    </p>
    <p>Artigo recebido em 14/07/10; revisado recebido em 25/10/10; aceito em 03/12/10. </p>
  </body>
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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">Predictors of global left ventricular function in metabolic syndrome</article-title>
      </title-group>
      <abstract xml:lang="en">
        <p>BACKGROUND: The metabolic syndrome (MS) represents a cluster of cardiovascular risk factors that act synergistically. OBJECTIVE: The aim of this study was to determine which parameters were independently associated with the global left ventricular (LV) function in subjects with MS estimated with the Tei index. METHODS: The study included 234 subjects with MS and 96 controls adjusted by age. MS was defined by the presence of three or more of ATP- NCEP III criteria. All subjects underwent laboratory blood tests and two-dimensional, pulsed and tissue Doppler echocardiography. Appropriate tissue Doppler time intervals for the estimation of the Tei index were also assessed. RESULTS: The Tei index was increased in subjects with MS (0.35 &#177; 0.05 vs 0.49 &#177; 0.10, p &lt; 0.001). Multiple regression analysis of the clinical parameters showed that systolic blood pressure (&#946;= 0.289, p &lt; 0.001), fasting glucose (&#946;= 0.205, p = 0.009), LV mass index (&#946;= 0.301, p &lt; 0.001), E/e'septal (&#946;= 0.267, p &lt; 0.001), and e'septal (&#946;= -0.176, p = 0.011) were independently associated with the global left ventricular function estimated by Tei index. CONCLUSION: MS has a significant impact on LV global function. Systolic blood pressure, fasting glucose, LV mass index, E/e'septal, and e'septal were independently associated with the LV global function.</p>
      </abstract>
      <kwd-group xml:lang="en">
        <kwd>Ventricular function left</kwd>
        <kwd>metabolic syndrome</kwd>
        <kwd>myocardial ischemia</kwd>
        <kwd>risk factors</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <p>
        <bold>ORIGINAL ARTICLE</bold>
      </p>
      <p>
        <fn id="enda-body2">
          <label>
            <bold>Predictors of global left ventricular function in metabolic syndrome</bold>
          </label>
          <p>
            <bold>Branislava Aleksa Ivanovic; Marijana Vaso Tadic; Dragan Vojislav Simic </bold>
          </p>
        </fn>
      </p>
      <p>Clinic for Cardiology, Clinical Centre of Serbia</p>
      <p>Mailing address</p>
      <p>
        <bold>ABSTRACT</bold>
      </p>
      <p><bold>BACKGROUND:</bold> The metabolic syndrome (MS) represents a cluster of cardiovascular risk factors that act synergistically. </p>
      <p><bold>OBJECTIVE:</bold> The aim of this study was to determine which parameters were independently associated with the global left ventricular (LV) function in subjects with MS estimated with the Tei index. </p>
      <p><bold>METHODS:</bold> The study included 234 subjects with MS and 96 controls adjusted by age. MS was defined by the presence of three or more of ATP- NCEP III criteria. All subjects underwent laboratory blood tests and two-dimensional, pulsed and tissue Doppler echocardiography. Appropriate tissue Doppler time intervals for the estimation of the Tei index were also assessed. </p>
      <p><bold>RESULTS:</bold> The Tei index was increased in subjects with MS (0.35 &#177; 0.05 <italic>vs</italic> 0.49 &#177; 0.10, p &lt; 0.001). Multiple regression analysis of the clinical parameters showed that systolic blood pressure (&#946;= 0.289, p &lt; 0.001), fasting glucose (&#946;= 0.205, p = 0.009), LV mass index (&#946;= 0.301, p &lt; 0.001), E/e'<sub>septal</sub> (&#946;= 0.267, p &lt; 0.001), and e'<sub>septal</sub> (&#946;= -0.176, p = 0.011) were independently associated with the global left ventricular function estimated by Tei index.</p>
      <p><bold>CONCLUSION:</bold> MS has a significant impact on LV global function. Systolic blood pressure, fasting glucose, LV mass index, E/e'<sub>septal</sub>, and e'<sub>septal</sub> were independently associated with the LV global function. </p>
      <p><bold>Keywords:</bold> Ventricular function left; metabolic syndrome; myocardial ischemia; risk factors. </p>
      <p>
        <bold>Introduction</bold>
      </p>
      <p>The myocardial performance index (the Tei index) reflects systolic and diastolic function of the left and right ventricles<sup>1</sup>. It could be impaired in patients with various risk factors such as hypertension<sup>2</sup>, diabetes<sup>3</sup>, and obesity<sup>4</sup>. The influence of the metabolic syndrome (MS) on global left ventricular function has not been completely determined. There are different opinions on this problem; on the one hand, there are authors who believe that MS is the cluster of risk factors and therefore the alteration of global left ventricular function is an expected and logical sequence<sup>5,6</sup>. On the other hand, some investigators have shown that the Tei index is not significantly altered in patients with a high prevalence of obesity, hypertension and diabetes, which are the important risk factors of metabolic syndrome<sup>7</sup>. A few studies have assessed the impact of individual MS risk factors on global left ventricular function. </p>
      <p>The aim of our study was to determine which clinical and echocardiographic parameters correlate with global left ventricle (LV) function in patients with MS, and also to identify which parameters were independently associated with the Tei index. </p>
      <p>
        <bold>Methods</bold>
      </p>
      <p>The investigation included 330 subjects divided into two groups: the first group involved 234 subjects (125 women and 109 men) with MS, while the control group included 96 subjects (52 women and 44 men) with no risk factors of MS. Patients with clinical or laboratory signs of heart failure, coronary artery disease, previous cerebrovascular insult, valvular heart disease, secondary hypertension or other chronic diseases such as cirrhosis of the liver, kidney failure, or endocrinological diseases (except diabetes mellitus type 2) were excluded from the study. MS was defined by the presence of three or more of the National Cholesterol Education Program's Adult Treatment Panel III (NCEP-ATP-III) criteria from 2001<sup>8</sup>: abdominal obesity (waist circumference <underline>&gt;</underline>102 cm in men and <underline>&gt;</underline> 88 cm in women), fasting triglycerides <underline>&gt;</underline>150 mg/dl, decreased HDL cholesterol (&lt; 40 mg/dl in men and &lt; 50 mg/dl in women), high blood pressure (<underline>&gt;</underline> 130/85 mmHg or antihypertensive therapy) and fasting glucose <underline>&gt;</underline> 110 mg/dl. </p>
      <p>The anthropometric measures (height, weight, waist circumference) were obtained from all subjects included in the study in order to calculate body surface area (BSA) and body mass index (BMI). Regarding laboratory analyses, fasting glucose, hemoglobin A1c, total cholesterol, low and high-density lipoprotein cholesterol (HDL, LDL), triglycerides, uric acid and serum creatinine levels were measured. </p>
      <p>Arterial blood pressure values were obtained by measuring the average value of two consecutive measurements in the sitting position with a five-minute interval in the morning hours, using a conventional sphygmomanometer. </p>
      <p>The diagnosis of diabetes was based on the criteria of the World Health Organization published in 2006<sup>9</sup> and arterial hypertension according to the recommendations of the European Association for Hypertension in 2007<sup>10</sup>. The protocol was approved by the Research Ethics Committee of the Faculty of Medicine, University of Belgrade. Informed consent was obtained from all participants. </p>
      <p>
        <bold>Echocardiography</bold>
      </p>
      <p>Echocardiographic examination was performed on an Acuson Sequoia 256 ultrasound system by using a 2-to-4 MHz transducer. The values of all echocardiographic parameters were obtained as the average value of five consecutive cardiac cycles. The left ventricular end-systolic (LVESD) and end-diastolic diameters (LVEDD), the left ventricular posterior wall (PWT) and interventricular septum thickness (IVS) were determined according to the recommendations of the American Society of Echocardiography<sup>11</sup>. End-systolic and end-diastolic volumes and parameters of systolic function (ejection fraction - EF and fractional shortening - FS) were estimated by using the Teicholz formula. Relative wall thickness (RWT) was calculated as (2xPWT)/LVEDD. </p>
      <p>The left ventricular mass (LVmass) was calculated by using Penn formula: LV mass = 1.04x[(LVEDD+ PWTD+IVS)<sup>3</sup>- (LVEDD)<sup>3</sup>] - 13,6 g<sup>12</sup>. The left ventricular mass index (LVmass/Ht<sup>2,7</sup>) was calculated as the ratio of the left ventricular mass and height<sup>2,7</sup>. The left ventricular hypertrophy was defined as LVmass/Ht<sup>2,7</sup><underline>&gt;</underline> 51 g/m<sup>2,7</sup> for men and <underline>&gt;</underline> 49.5 g/m<sup>2,7 </sup>for women<sup>13</sup>. </p>
      <p>The analysis of transmitral inflow velocities was obtained by pulsed-wave Doppler in the apical four-chamber view with the sample volume placed at the mitral valve leaflet tips<sup>14</sup>. Measurements included the transmitral early diastolic (E-wave) and atrial (A-wave) velocities to calculate E/A ratio and E-wave deceleration time (DT)<sup>13</sup>. </p>
      <p>Tissue Doppler imaging was used to obtain LV myocardial velocities in the apical four-chamber view with a 2-mm sample volume placed at the septal segment of the mitral annulus during early diastole (e&#180;<sub>septal</sub>) and systole (s<sub>septal</sub>)<sup>14</sup>. The E/e&#180;<sub>septal</sub> ratio was determined using previously estimated values of E and e&#180;<sub>septal</sub> flow velocities during early diastole obtained by pulsed and tissue Doppler. </p>
      <p>The parameters necessary for the calculation of the Tei index were obtained by tissue Doppler in the apical four-chamber view<sup>15</sup>. A 2-mm sample volume was placed at the lateral corner of the mitral annulus. The isovolumetric contraction time (IVCT) and isovolumetric relaxation time (IVRT) were measured from the end of the mitral annular velocity pattern to the onset of the S-wave and from the end of the S-wave to the onset of the mitral annular velocity pattern, respectively. The ejection time (ET) was defined as the duration of the LV outflow Doppler velocity profile. The Tei index was calculated according to the formula: Tei index = (IVCT + IVRT)/ET<sup>1</sup>. </p>
      <p>
        <bold>Statistical analyses</bold>
      </p>
      <p>Continuous variables were presented as mean &#177; standard deviation (SD) and were compared by t-test for two independent samples, as they showed a normal distribution. Differences in proportions were compared by using &#967;<sup>2</sup> test. Pearson&#180;s correlation coefficient was used for determination of correlation between the Tei index and different clinical and echocardiographic parameters. The same test was used for correlation determination between these parameters and tissue Doppler intervals, which were required for the calculation of the Tei index (IVRT, IVCT and ET). Stepwise multiple variable regression analysis determined which parameters, clinical and echocardiographic, were independently associated with the Tei index or its components (IVRT, IVCT and ET). Heart rate and the variable of which p-value <underline>&lt;</underline> 0.10 were entered in the stepwise regression models. We also determined which MS components correlated with and which components were independently associated with the Tei index. A p-value &lt; 0.05 was considered statistically significant. </p>
      <p>
        <bold>Results</bold>
      </p>
      <p>There was no statistically important difference in mean age between the subjects with MS and controls (52 &#177; 9 <italic>vs</italic> 54 &#177; 9 years, p &gt; 0.05). All clinical parameters of the study group are shown in <xref ref-type="table" rid="tab1-body2">Table 1</xref>. Values of all the parameters of MS were significantly higher in patients with MS compared to controls (<xref ref-type="table" rid="tab1-body2">Table 1</xref>). We also found that the levels of hemoglobin A1c, uric acid, serum creatine, LDL cholesterol and total cholesterol were significantly higher in the population of patients with MS (<xref ref-type="table" rid="tab1-body2">Table 1</xref>). </p>
      <table-wrap id="tab1-body2">
        <graphic xlink:href="1678-4170-abc-96-05-0377-00039-gt01-en.jpg"/></table-wrap>
      <p>There were no statistically important differences between the observed groups regarding LV diameters, ejection fraction and fractional shortening (<xref ref-type="table" rid="tab2-body2">Table 2</xref>). Relative wall thickness and LV mass index were significantly increased in the MS group (<xref ref-type="table" rid="tab2-body2">Table 2</xref>). Compared to the control group, MS subjects had significantly higher percentage of LV hypertrophy (<xref ref-type="table" rid="tab2-body2">Table 2</xref>). </p>
      <table-wrap id="tab2-body2">
        <graphic xlink:href="1678-4170-abc-96-05-0377-00039-gt02-en.jpg"/></table-wrap>
      <p>The systolic function parameter obtained by tissue Doppler (s<sub>septal</sub>) demonstrated normal LV systolic function in subjects with MS. However, the LV diastolic function parameters such as E/A, DT, e'<sub>septal</sub> and E/e'<sub>septal</sub> were significantly deteriorated in the group with MS (<xref ref-type="table" rid="tab2-body2">Table 2</xref>). </p>
      <p>The parameters required for calculation of the Tei index were also altered in subjects with MS. IVRT and IVCT were significantly prolonged, while the ET was shortened in the MS group, which determined the increased value of the Tei index (<xref ref-type="table" rid="tab2-body2">Table 2</xref>). </p>
      <p>Univariate correlation analyses showed that heart rate, systolic and diastolic blood pressure, levels of glucose, triglycerides, total cholesterol and serum creatinine, and waist circumference were associated with LV global function estimated by the Tei index (<xref ref-type="table" rid="tab3-body2">Table 3</xref>). Among the echocardiographic parameters, univariate correlation analyses found that relative wall thickness, the left atrial diameter, the left ventricular mass index, E/A ratio, s<sub>septal</sub>, e'<sub>septal</sub> and E/e'<sub>septal</sub> ratio correlated with the myocardial performance index of the left ventricle (<xref ref-type="table" rid="tab3-body2">Table 3</xref>). Multiple regression analysis of clinical and echocardiographic parameters demonstrated that systolic blood pressure, glucose level, left ventricular mass index and e'<sub>septal</sub> and E/e'<sub>septal</sub> ratio were independently associated with the global LV function estimated by the Tei index (<xref ref-type="table" rid="tab4-body2">Table 4</xref>). </p>
      <table-wrap id="tab3-body2">
        <graphic xlink:href="1678-4170-abc-96-05-0377-00039-gt03-en.jpg"/></table-wrap>
      <table-wrap id="tab4-body2">
        <graphic xlink:href="1678-4170-abc-96-05-0377-00039-gt04-en.jpg"/></table-wrap>
      <p>Additionally, we determined which parameters were associated with all time intervals used in the Tei index equation (IVRT, IVCT and ET). </p>
      <p>The univariate analysis of clinical and echocardiographic parameters in the MS group showed that systolic blood pressure, fasting glucose level, waist circumference, relative wall thickness, left atrial diameter, left ventricular mass index, E/A ratio, deceleration time, e'<sub>septal</sub> and E/e'<sub>septal</sub> ratio were associated with IVRT (<xref ref-type="table" rid="en_aop03011tab05m-body2">Table 5</xref>). Moreover, all these parameters except the left atrial diameter, E/A ratio and deceleration time were independently associated with IVRT (<xref ref-type="table" rid="en_aop03011tab06m-body2">Table 6</xref>). </p>
      <p content-type="asset">
        <table-wrap id="en_aop03011tab05m-body2">
          <graphic xlink:href="1678-4170-abc-96-05-0377-00039-gt05-en.jpg"/></table-wrap>
      </p>
      <p content-type="asset">
        <table-wrap id="en_aop03011tab06m-body2">
          <graphic xlink:href="1678-4170-abc-96-05-0377-00039-gt06-en.jpg"/></table-wrap>
      </p>
      <p>The correlation analysis revealed that systolic and diastolic blood pressure, fasting glucose level, waist circumference, relative wall thickness, left atrial diameter, left ventricular mass index, E/A ratio, deceleration time, e'<sub>septal</sub> and E/e'<sub>septal</sub> ratio were associated with IVCT (<xref ref-type="table" rid="en_aop03011tab05m-body2">Table 5</xref>). All mentioned parameters, except diastolic blood pressure, were independently associated with IVCT (<xref ref-type="table" rid="en_aop03011tab06m-body2">Table 6</xref>). </p>
      <p>The univariate analysis also demonstrated that systolic blood pressure, left atrial diameter, left ventricular mass index, ejection fraction, s<sub>septal</sub>, deceleration time, e'<sub>septal</sub> and E/e'<sub>septal</sub> ratio were associated with ET (<xref ref-type="table" rid="en_aop03011tab05m-body2">Table 5</xref>). However, only systolic blood pressure, left ventricular mass index, ejection fraction, and s<sub>septal</sub> were independently associated with ET (<xref ref-type="table" rid="en_aop03011tab06m-body2">Table 6</xref>). </p>
      <p>Correlation analysis showed that all components of MS except HDL were associated with the Tei index, but only systolic blood pressure, fasting glucose and levels of triglycerides were independently associated with this global LV function parameter (<xref ref-type="table" rid="tab7-body2">Table 7</xref>). </p>
      <table-wrap id="tab7-body2">
        <graphic xlink:href="1678-4170-abc-96-05-0377-00039-gt07-en.jpg"/></table-wrap>
      <p>
        <bold>Discussion</bold>
      </p>
      <p>The Tei index is a unique echocardiographic parameter that simultaneously shows the systolic and diastolic function of a ventricle. </p>
      <p>There is no absolute agreement about the impact of age and heart rate on the Tei index<sup>2,3,5,7,16</sup>. Our research showed that the index of global LV function was independent from age, which is very important for the assessment of LV global function in patients of different ages. On the other hand, this study revealed that heart rate correlated with the Tei index, although not independently. Similar results were obtained in other studies<sup>2,17</sup>. </p>
      <p>Arterial hypertension changes the myocardial structure, primarily due to abnormal accumulation of collagen in the extracellular space, resulting in a decrease of compliance and occurrence of LV diastolic dysfunction<sup>18</sup>. </p>
      <p>There is no universal opinion about the influence of systolic and diastolic arterial blood pressure on the global LV function and the Tei index. Some authors showed that the Tei index correlated with the arterial blood pressure<sup>5,15,19</sup>, while others have disagreed<sup>2,17</sup>. Our investigation revealed that the systolic and diastolic blood pressure correlated with the myocardial performance index, but only systolic blood pressure was independently associated with the Tei index. The same result was obtained when we considered only MS criteria. Moreover, systolic blood pressure was shown to be the strongest independent predictor of the Tei index among MS criteria with the highest statistical significance (p &lt; 0.001). </p>
      <p>Insulin resistance underlying type 2 diabetes mellitus and MS leads to significant changes in the structure and function of the left ventricle. Basically, it leads to the activation of the sympathetic nervous system and RAAS, causing reduction in the number of mitochondria, contractile elements, capillary network density and induces extracellular fibrosis and apoptosis<sup>20</sup>. All these changes result in the onset of LV diastolic dysfunction, and subsequently, in LV hypertrophy. Pattoneri et al<sup>3</sup> showed that people with recently diagnosed type 2 diabetes mellitus have abnormal global LV function. There is a dilemma as to whether the levels of glucose and glycated hemoglobin affect the global LV function. Studies have confirmed that this correlation exists<sup>3,5,19</sup>, which was also the result of our study. The separate analysis of the influence MS components in our study also showed that fasting glucose levels, in addition to systolic blood pressure and triglycerides levels, were independently associated with the Tei index. </p>
      <p>The investigations that assessed individual and simultaneous effects of hypertension and diabetes on global LV function did not agree as to whether these factors synergistically lead to greater LV damage. Cho et al<sup>21</sup> showed that the concurrent effects of these factors changed global LV function more than individual factors separately. Other authors disagree and believe that differences between the individual and the simultaneous effects of these two factors do not exist<sup>3,17</sup>. </p>
      <p>There is no absolute agreement on the impact of obesity on the Tei index. Levent et al<sup>4</sup> studied the effect of hypertension and obesity in children and revealed that obese, but normotensive children had a significantly higher Tei index compared to the control group, which confirmed impaired global LV function, whereas children with both risk factors had even greater levels of dysfunction, which indicated a possible synergistic effect of these factors. The study in an adult population confirmed that obesity impaired global myocardial function by decreasing the Tei index, i.e., improving myocardial function through weight reduction<sup>22</sup>. There is a controversial study that showed that obesity did not worsen, but improved global LV function<sup>23</sup>. However, the authors did not suggest possible mechanisms for this "protective" effect of increased body weight. Our research showed that BMI did not correlate with the Tei index, in contrast with waist circumference, which was an independent predictor of global LV function. These findings were expected, as there was no significant difference in BMI between the MS and control group, while waist circumference was significantly higher in MS subjects. Voulgari et al<sup>19</sup> obtained similar results. </p>
      <p>In this study, we showed that the levels of LDL and HDL cholesterol were not correlated with the Tei index, while the levels of total cholesterol and triglycerides correlated with this parameter. Triglycerides levels were not independently associated with the Tei index when all clinical and echocardiographic parameters were considered. However, when only MS criteria were considered, triglycerides were independently associated with this index, which is consistent with the findings of other authors<sup>5,19</sup>. Fuentes et al<sup>24</sup> were the first to show that subjects with increased levels of triglycerides had significantly impaired LV diastolic function and increased LV mass, when compared to the control group. This is explained by the fact that the triglycerides accumulated in extracellular space reduce LV compliance, hence their lipotoxic effects on cardiomyocytes and high energy consumption, which is necessary for their metabolism. </p>
      <p>Our investigation also showed that renal function estimated by serum creatinine was elevated in MS subjects and correlated with the Tei index which is in agreement with some authors<sup>25</sup>, but is contradictory to others<sup>26</sup>. However, serum creatinine was not independently associated with Tei index. </p>
      <p>The relationship between various echocardiographic parameters and the Tei index was evaluated in patients with hypertension, diabetes or those who had both risk factors<sup>2,3,17</sup>, but this assessment had not been previously carried out in subjects with metabolic syndrome. Most authors believe that impaired global LV function in metabolic syndrome is actually a consequence of damaged diastolic function<sup>5,6,19</sup>, which is mostly the result of the LV systolic function identification only by the systolic ejection fraction and/or the left ventricular fractional shortening. However, there have been studies that showed that these parameters could also be altered in subjects with MS<sup>26</sup>. The tissue Doppler imaging introduced new LV systolic function parameters, which showed its impairment in the MS group<sup>27</sup>. Our investigation showed that the LV systolic function estimated by the ejection fraction and s<sub>septal</sub> was preserved in the MS group, although with borderline statistical significance. </p>
      <p>All the LV diastolic function parameters (E/A, DT, e'<sub>septal</sub> and E/e'<sub>septal</sub>) assessed in our study confirmed the existence of diastolic dysfunction. Relative wall thickness and LV mass index, left atrial diameter, E/A ratio, s<sub>septal</sub>, e'<sub>septal</sub> and E/e'<sub> septal</sub> were correlated with global LV function estimated by the Tei index; however the LV mass index, e'<sub>septal</sub> and E/e'<sub>septal</sub> were independently associated with the Tei index. Similar results were obtained by Masugata et al<sup>2</sup> in patients with hypertension. Anderson et al<sup>17</sup> discovered a correlation of the Tei index and DT and E/A ratio in patients with hypertension and diabetes, while Pattoneri et al<sup>3</sup> found a correlation of IVCT and ET with this index in patients with recently diagnosed diabetes. </p>
      <p>Additionally, we studied the impact of different clinical and echocardiographic parameters in the MS group on tissue Doppler intervals needed for the calculation of the Tei index (IVRT, IVCT and ET). Systolic blood pressure, fasting glucose level, waist circumference, relative wall thickness, LV mass index, e'<sub>septal</sub> and E/e'<sub>septal</sub> were independently associated with IVRT. The multivariate analysis showed that systolic and diastolic blood pressure, fasting glucose level, LV mass index, e'<sub>septal</sub> and E/e'<sub>septal</sub> were independently associated with IVCT. These parameters simultaneously represent LV systolic and diastolic function in the Tei index equation. On the other hand ET, a parameter of systolic function in this equation, was independently associated with systolic blood pressure, LV mass index, ejection fraction, and s<sub>septal</sub>. Apparently, almost the same factors that are associated with IVRT, IVCT and ET in MS correlated with the Tei index as a parameter of global LV function. These findings are important, as we have shown that it is not necessary to determine risk factors for individual components of the Tei index. </p>
      <p>As the LV systolic function was preserved in subjects with metabolic syndrome in our research, whereas LV diastolic function was damaged, the logical conclusion is that the impairment of global LV function is actually the result of altered diastolic function. However, a larger study group would possibly have shown that systolic LV function is also altered in MS subjects, as the statistical value in our research was borderline (p = 0.075). </p>
      <p>The limitation of this study was a large number of MS subjects with arterial hypertension, which was controlled by different medications that could also affect the Tei index and result interpretation. . Another limitation is the fact that a few clinical trials used tissue Doppler imaging to obtain parameters of LV systolic, diastolic and global function; therefore, we could not carry out a full comparison of these parameters. Diagnostic studies demonstrated that the Tei index obtained from the pulsed and the tissue Doppler has very similar values and although it has been proven that the values estimated by the tissue Doppler are more precise and more correlated with invasive measurements obtained during cardiac catheterization, the comparison is quite reasonable<sup>28</sup>. The third limitation concerned the preload dependence of the Tei index<sup>29</sup>. </p>
      <p>
        <bold>Conclusion</bold>
      </p>
      <p>Metabolic syndrome leads to subclinical cardiac damage, reducing the global LV function. The Tei index is a relatively simple way to estimate global LV function and therefore, a valuable parameter in everyday clinical practice. Multiple regression analysis of clinical parameters showed that systolic blood pressure, fasting glucose, LV mass index, E/e'<sub>septal</sub>, and e'<sub>septal</sub> were independently associated with LV global function estimated by the Tei index. We have also shown that almost the same factors which are associated with IVRT, IVCT and ET in MS group are also associated with the Tei index. The impaired LV diastolic function is the main reason for deterioration of the global LV function in MS, according to our research. Additionally we showed that, among the components of MS, only systolic blood pressure, fasting glucose and triglycerides levels were independently associated with LV global function. </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>
  <sub-article article-type="translation" id="TRes" xml:lang="es">
    <front-stub>
      <article-categories/>
      <title-group>
        <article-title xml:lang="es">Predictores de funci&#243;n ventricular izquierda global en el s&#237;ndrome metab&#243;lico</article-title>
      </title-group>
      <abstract xml:lang="es">
        <p>FUNDAMENTO: El s&#237;ndrome metab&#243;lico (SM) representa un conjunto de factores de riesgo cardiovascular que act&#250;an de forma sin&#233;rgica. OBJETIVO: El objetivo de este estudio fue determinar cuales par&#225;metros estaban asociados de forma independiente a la funci&#243;n global del ventr&#237;culo izquierdo (VI) en individuos con SM, estimada a trav&#233;s del &#237;ndice Tei. M&#201;TODOS: El estudio incluy&#243; 234 individuos con SM y 96 controles ajustados por edad. El SM fue definido por la presencia de tres o m&#225;s criterios ATP-NCEP III. Todos los individuos fueron sometidos a tests de laboratorio y ecocardiograma bidimensional y con Doppler pulsado y tisular. Intervalos de tiempo apropiados en el Doppler tisular para la estimativa del &#237;ndice Tei tambi&#233;n fueron evaluados. RESULTADOS: El &#237;ndice Tei estaba aumentado en todos los individuos con SM (0,35 &#177; 0,05 vs 0,49 &#177; 0,10, p &lt; 0,001). An&#225;lisis de regresi&#243;n m&#250;ltiple de los par&#225;metros cl&#237;nicos mostr&#243; que la presi&#243;n arterial sist&#243;lica (&#946; = 0,289, p &lt; 0,001), glucemia de ayuno (&#946; = 0,205, p = 0,009), &#237;ndice de masa del VI (&#946; = 0,301, p &lt; 0,001), E/e'septal (&#946; = 0,267, p &lt; 0,001) y e'septal (&#946; = -0,176, p = 0,011) estaban independientemente asociados con la funci&#243;n ventricular izquierda global estimada por el &#237;ndice Tei. CONCLUSI&#211;N: El SM tuvo un impacto significativo en la funci&#243;n global del VI. La presi&#243;n arterial sist&#243;lica, glucemia de ayuno, &#237;ndice de masa del VI E/e'septal, y e'septal estaban independientemente asociados con la funci&#243;n global del VI. (Arq Bras Cardiol 2011;96(5):377-385)</p>
      </abstract>
      <kwd-group xml:lang="es">
        <kwd>Funci&#243;n ventricular izquierda</kwd>
        <kwd>s&#237;ndrome metab&#243;lico</kwd>
        <kwd>isquemia mioc&#225;rdica</kwd>
        <kwd>factores de riesgo</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <p>
        <bold>ART&#205;CULO ORIGINAL</bold>
      </p>
      <p><undefined id="topo-body3"/>Predictores de funci&#243;n ventricular izquierda global en el s&#237;ndrome metab&#243;lico</p>
      <p>
        <bold>Branislava Aleksa Ivanovic; Marijana Vaso Tadic; Dragan Vojislav Simic</bold>
      </p>
      <p>Clinic for Cardiology, Clinical Centre of Serbia, Belgrado - S&#233;rvia</p>
      <p>Correspondencia</p>
      <p>
        <bold>RESUMEN</bold>
      </p>
      <p><bold>FUNDAMENTO:</bold> El s&#237;ndrome metab&#243;lico (SM) representa un conjunto de factores de riesgo cardiovascular que act&#250;an de forma sin&#233;rgica.</p>
      <p><bold>OBJETIVO:</bold> El objetivo de este estudio fue determinar cuales par&#225;metros estaban asociados de forma independiente a la funci&#243;n global del ventr&#237;culo izquierdo (VI) en individuos con SM, estimada a trav&#233;s del &#237;ndice Tei.</p>
      <p><bold>M&#201;TODOS:</bold> El estudio incluy&#243; 234 individuos con SM y 96 controles ajustados por edad. El SM fue definido por la presencia de tres o m&#225;s criterios ATP-NCEP III. Todos los individuos fueron sometidos a tests de laboratorio y ecocardiograma bidimensional y con Doppler pulsado y tisular. Intervalos de tiempo apropiados en el Doppler tisular para la estimativa del &#237;ndice Tei tambi&#233;n fueron evaluados.</p>
      <p><bold>RESULTADOS:</bold> El &#237;ndice Tei estaba aumentado en todos los individuos con SM (0,35 &#177; 0,05 <italic>vs</italic> 0,49 &#177; 0,10, p &lt; 0,001). An&#225;lisis de regresi&#243;n m&#250;ltiple de los par&#225;metros cl&#237;nicos mostr&#243; que la presi&#243;n arterial sist&#243;lica (&#946; = 0,289, p &lt; 0,001), glucemia de ayuno (&#946; = 0,205, p = 0,009), &#237;ndice de masa del VI (&#946; = 0,301, p &lt; 0,001), E/e'<sub>septal</sub> (&#946; = 0,267, p &lt; 0,001) y e'<sub>septal</sub> (&#946; = -0,176, p = 0,011) estaban independientemente asociados con la funci&#243;n ventricular izquierda global estimada por el &#237;ndice Tei.</p>
      <p><bold>CONCLUSI&#211;N:</bold> El SM tuvo un impacto significativo en la funci&#243;n global del VI. La presi&#243;n arterial sist&#243;lica, glucemia de ayuno, &#237;ndice de masa del VI E/e'<sub>septal</sub>, y e'<sub>septal</sub> estaban independientemente asociados con la funci&#243;n global del VI. (Arq Bras Cardiol 2011;96(5):377-385)</p>
      <p><bold>Palabras clave:</bold> Funci&#243;n ventricular izquierda, s&#237;ndrome metab&#243;lico, isquemia mioc&#225;rdica, factores de riesgo.</p>
      <p>
        <bold>Introducci&#243;n</bold>
      </p>
      <p>El &#237;ndice de desempe&#241;o mioc&#225;rdico (&#237;ndice Tei) refleja las funciones sist&#243;lica y diast&#243;lica de los ventr&#237;culos izquierdo y derecho<sup>1</sup>. Puede ser deficiente en pacientes con varios factores de riesgo, tales como hipertensi&#243;n<sup>2</sup>, diabetes<sup>3</sup> y obesidade<sup>4</sup>. La influencia del s&#237;ndrome metab&#243;lico (SM) en la funci&#243;n global del ventr&#237;culo izquierdo (VI) aun no fue determinada de forma completa. Hay diferentes opiniones sobre ese problema; por un lado hay autores que creen que el SM es un conjunto de factores de riesgo y, siendo as&#237;, la alteraci&#243;n en la funci&#243;n global del VI es una consecuencia esperada y l&#243;gica<sup>5,6</sup>. Por otro lado, algunos investigadores mostraron que el &#237;ndice Tei no est&#225; alterado de forma significativa en pacientes con alta prevalencia de obesidad, hipertensi&#243;n y diabetes, los cuales son factores de riesgo importantes del s&#237;ndrome metab&#243;lico<sup>7</sup>. Pocos estudios analizaron el impacto de los factores de riesgo individuales del SM en la funci&#243;n global del VI.</p>
      <p>El objetivo del presente estudio fue determinar cuales par&#225;metros cl&#237;nicos y ecocardiogr&#225;ficos se correlacionan con la funci&#243;n global del VI en pacientes con SM y tambi&#233;n identificar cuales par&#225;metros estaban asociados de forma independiente con el &#237;ndice Tei.</p>
      <p>
        <bold>Metodolog&#237;a</bold>
      </p>
      <p>La investigaci&#243;n incluy&#243; 330 individuos divididos en dos grupos: el primer grupo consist&#237;a en 234 individuos (125 mujeres y 109 hombres) con SM, mientras que el grupo control consist&#237;a en 96 individuos (52 mujeres y 44 hombres) sin factores de riesgo de SM. Pacientes con se&#241;ales cl&#237;nicas o de laboratorio de insuficiencia card&#237;aca, enfermedad arterial coronaria, lesi&#243;n cerebrovascular anterior, enfermedad valvar card&#237;aca, hipertensi&#243;n secundaria u otras enfermedades cr&#243;nicas tales como cirrosis hep&#225;tica, insuficiencia renal o enfermedades endocrinol&#243;gicas (excepto diabetes mellitus tipo 2) fueron excluidos del estudio. SM fue definido por la presencia de tres o m&#225;s criterios del <italic>Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III - NCEP-ATP-III) </italic>de 2001<sup>8</sup>: obesidad abdominal (circunferencia de la cintura <underline>&gt;</underline> 102 cm en hombres y <underline>&gt;</underline> 88 cm en mujeres), triglic&#233;ridos de ayuno <underline>&gt;</underline> 150 mg/dl, niveles disminuidos de HDL colesterol (&lt; 40 mg/dl en hombres y &lt; 50 mg/dl en mujeres), presi&#243;n arterial elevada (<underline>&gt;</underline> 130/85 mmHg o terapia antihipertensiva) y glucemia de ayuno <underline>&gt;</underline> 110 mg/dl. </p>
      <p>Las medidas antropom&#233;tricas (altura, peso, circunferencia de la cintura) fueron obtenidas de todos los individuos incluidos en el estudio a fin de calcular el &#225;rea de superficie corporal (ASC) e &#237;ndice de masa corporal (IMC). En relaci&#243;n al an&#225;lisis de laboratorio, utilizamos los niveles de glucemia de ayuno, hemoglobina glicosilada, colesterol total y lipoprote&#237;na de alta y baja densidad colesterol (HDL y LDL, respectivamente), triglic&#233;ridos, &#225;cido &#250;rico y creatinina s&#233;rica.</p>
      <p>Los valores de la presi&#243;n arterial (PA) fueron obtenidos a trav&#233;s de la medida del valor medio de dos mediciones consecutivas en la posici&#243;n sentada con un intervalo de cinco minutos, por la ma&#241;ana, utilizando un esfigmoman&#243;metro convencional. </p>
      <p>El diagn&#243;stico de diabetes fue basado en los criterios de la Organizaci&#243;n Mundial de la Salud (OMS) publicados en 2006<sup>9</sup> y hipertensi&#243;n arterial fue establecida de acuerdo con las recomendaciones de la European Association for Hypertension en 2007<sup>10</sup>. El protocolo fue aprobado por el Comit&#233; de &#201;tica de la Facultad de Medicina de la Universidad de Belgrado. Consentimiento informado fue obtenido de todos los participantes.</p>
      <p>
        <bold>Ecocardiograf&#237;a</bold>
      </p>
      <p>El examen ecocardiogr&#225;fico fue realizado con el ecocardiografo Acuson Sequoia 256 con un transductor de 2 a 4 MHz. Los valores de todos los par&#225;metros ecocardiogr&#225;ficos fueron obtenidos como el valor medio de cinco ciclos card&#237;acos consecutivos. El di&#225;metro sist&#243;lico final del VI (DSFVI) y el di&#225;metro diast&#243;lico final del VI (DDFVI), el espesor de la pared posterior (EPP) del VI y la del septo interventricular (ESI) fueron determinados de acuerdo con las recomendaciones de la <italic>American Society of Echocardiography</italic><sup>11</sup>. Los vol&#250;menes finales sist&#243;lico y diast&#243;lico del VI y par&#225;metros de la funci&#243;n sist&#243;lica (fracci&#243;n de eyecci&#243;n - FE y acortamiento fraccional - AF) fueron estimados por la f&#243;rmula de Teichholz. El espesor relativo de la pared (ERP) fue calculado como (2x PWT)/DDFVI.</p>
      <p>La masa ventricular izquierda (MVI) fue calculada a trav&#233;s de la f&#243;rmula de Penn: MVI = 1.04x[(DDFVI + EPPD + ESI)<sup>3</sup> - (DDFVI)<sup>3</sup> - 13,6 g<sup>12</sup>. El &#237;ndice de masa del VI (masa del VI/Alt<sup>2,7</sup>) fue calculado como la raz&#243;n entre la masa ventricular izquierda y la altura<sup>2,7</sup>. Hipertrofia ventricular izquierda fue definida como masa VI/Alt<sup>2,7</sup><underline>&gt;</underline> 51 g/m<sup>2,7</sup> para hombres y <underline>&gt;</underline> 49,5 g/m<sup>2,7 </sup>para mujeres<sup>13</sup>.</p>
      <p>El an&#225;lisis de las velocidades de flujo transmitral fue obtenido por Doppler pulsada en el corte apical cuatro c&#225;maras con el volumen de la muestra posicionado en las puntas de las hojas de la valva mitral<sup>14</sup>. Las medidas incluyeron las velocidades diast&#243;lica inicial transmitral (onda E) y atrial (onda A) para calcular la raz&#243;n E/A y el tiempo de desaceleraci&#243;n (TD) de la onda E<sup>13</sup>. La imagen del Doppler tisular fue utilizada para obtener las velocidades mioc&#225;rdicas del VI en el corte apical cuatro c&#225;maras con volumen de muestra de 2 mm posicionado en el segmento septal del anillo mitral durante la di&#225;stole inicial (e&#180;<sub>septal</sub>) y s&#237;stole (s<sub>septal</sub>)<sup>14</sup>. La raz&#243;n E/e&#180;<sub>septal</sub> fue determinada a trav&#233;s de valores previamente estimados de velocidades de flujo E y e'<sub>septal</sub> en la di&#225;stole inicial obtenidas por Doppler tisular y pulsado. </p>
      <p>Los par&#225;metros necesarios para calcular el &#237;ndice Tei fueron obtenidos atrav&#233;s de Doppler tisular en el corte apical cuatro c&#226;maras<sup>15</sup>. Un volumen de muestra de 2 mm fue posicionado en el canto lateral del anillo mitral. EL tiempo de contracci&#243;n isovolum&#233;trica (TCIV) y el tiempo de relajaci&#243;n isovolum&#233;trico (TRIV) fueron medidos del final del est&#225;ndar de velocidad del anillo mitral hasta el inicio de la onda S y del final de la onda S hasta el inicio del est&#225;ndar de velocidad del anillo mitral, respectivamente.</p>
      <p>El tiempo de eyecci&#243;n (TE) fue definido como la duraci&#243;n del flujo de salida del VI en el perfil de velocidad del Doppler. </p>
      <p>El &#237;ndice Tei fue calculado de acuerdo con la f&#243;rmula: &#205;ndice Tei = (TCIV + TRIV)/TE<sup>1</sup>.</p>
      <p>
        <bold>An&#225;lisis estad&#237;sticos</bold>
      </p>
      <p>Variables continuas fueron presentadas como medias &#177; desviaciones-est&#225;ndar (DE) y comparadas a trav&#233;s de test <italic>t</italic> para dos muestras independientes, considerando que presentaban distribuci&#243;n normal. Diferencias entre proporciones fueron comparadas usando test &#967;&#178;. El coeficiente de correlaci&#243;n de Pearson fue utilizado para determinar la correlaci&#243;n entre el &#237;ndice Tei y a diferentes par&#225;metros cl&#237;nicos y ecocardiogr&#225;ficos. El mismo test fue usado para determinar la correlaci&#243;n entre esos par&#225;metros e intervalos del Doppler tisular que eran necesarios para el c&#225;lculo del &#237;ndice Tei (TRIV, TCIV y TE). El an&#225;lisis de regresi&#243;n m&#250;ltiple <italic>stepwise</italic> determin&#243; cuales par&#225;metros, cl&#237;nicos y ecocardiogr&#225;ficos, estaban asociados de forma independiente con el &#237;ndice Tei o sus componentes (TRIV, TCIV y TE). Frecuencia card&#237;aca y la variable con p &lt; 0,10 en los an&#225;lisis de correlaci&#243;n entraron en el an&#225;lisis de regresi&#243;n m&#250;ltiple <italic>stepwise</italic>. Tambi&#233;n determinamos cuales componentes de la SM se correlacionaban y cuales componentes estaban independientemente asociados con el &#237;ndice Tei. Un valor de p &lt; 0,05 fue considerado estad&#237;sticamente significativo.</p>
      <p>
        <bold>Resultados</bold>
      </p>
      <p>No hab&#237;a diferencia estad&#237;sticamente significativa en la media de la edad entre los individuos con SM y los controles (52 &#177; 9 <italic>vs</italic> 54 &#177; 9 a&#241;os, p &gt; 0,05). Todos los par&#225;metros cl&#237;nicos del grupo de estudio son mostrados en la <xref ref-type="table" rid="t1-body3">Tabla 1</xref>. Los valores de todos los par&#225;metros del SM eran significativamente m&#225;s altos en los pacientes con SM que en los controles (<xref ref-type="table" rid="t1-body3">Tabla 1</xref>). Tambi&#233;n observamos que los niveles de hemoglobina glicosilada, acido &#250;rico, creatinina s&#233;rica, LDL-colesterol y colesterol total eran significativamente m&#225;s altos en la poblaci&#243;n de pacientes con SM (<xref ref-type="table" rid="t1-body3">Tabla 1</xref>).</p>
      <table-wrap id="t1-body3">
        <graphic xlink:href="1678-4170-abc-96-05-0377-00039-gt01-es.jpg"/></table-wrap>
      <p>No hab&#237;a diferencia estad&#237;sticamente significativa entre los grupos estudiados en relaci&#243;n al di&#225;metro del VI, FE y AF (<xref ref-type="table" rid="t2-body3">Tabla 2</xref>). El espesor relativo de la pared y el &#237;ndice de masa del VI estaban significativamente aumentados en el grupo con SM (<xref ref-type="table" rid="t2-body3">Tabla 2</xref>). Comparado al grupo control, el grupo SM presentaba un porcentaje significativamente mayor de hipertrofia del VI (<xref ref-type="table" rid="t2-body3">Tabla 2</xref>).</p>
      <table-wrap id="t2-body3">
        <graphic xlink:href="1678-4170-abc-96-05-0377-00039-gt02-es.jpg"/></table-wrap>
      <p>El par&#225;metro de la funci&#243;n sist&#243;lica obtenido a trav&#233;s de Doppler tisular (s<sub>septal</sub>) demostr&#243; funci&#243;n sist&#243;lica del VI normal en individuos con SM. Entre tanto, los par&#225;metros de la funci&#243;n diast&#243;lica del VI, como E/A, TD, e'<sub>septal</sub> y E/e'<sub>septal</sub> se presentaban significativamente deteriorados en el grupo con SM (<xref ref-type="table" rid="t2-body3">Tabla 2</xref>).</p>
      <p>Los par&#225;metros necesarios para el c&#225;lculo del &#237;ndice Tei tambi&#233;n estaban alterados en individuos con SM. EL TRIV y TCIV se presentaban significativamente prolongados, mientras que el TE estaba acortado en el grupo SM, lo que determinaba el valor aumentado del &#237;ndice Tei (<xref ref-type="table" rid="t2-body3">Tabla 2</xref>). </p>
      <p>An&#225;lisis de correlaci&#243;n univariado mostraron que FC, presi&#243;n arterial sist&#243;lica (PAS), presi&#243;n arterial diast&#243;lica (PAD), niveles de glucosa, triglic&#233;ridos, colesterol total y creatinina s&#233;rica y valores de circunferencia de la cintura (CC) estaban asociados con la funci&#243;n global del VI estimada por el &#237;ndice Tei (<xref ref-type="table" rid="t3-body3">Tabla 3</xref>). Entre los par&#225;metros ecocardiogr&#225;ficos, los an&#225;lisis de correlaci&#243;n univariada demostraron que el espesor relativo de la pared, di&#225;metro atrial izquierdo, &#237;ndice de masa del VI, raz&#243;n E/A, s<sub>septal</sub>, e'<sub>septal</sub> y raz&#243;n E/e'<sub>septal</sub> se correlacionaban con el &#237;ndice de desempe&#241;o mioc&#225;rdico del VI (<xref ref-type="table" rid="t3-body3">Tabla 3</xref>). El an&#225;lisis de regresi&#243;n m&#250;ltiple de los par&#225;metros cl&#237;nicos y ecocardiogr&#225;ficos demostr&#243; que la PAS, nivel de glucosa, &#237;ndice de masa del VI, e'<sub>septal</sub> y raz&#243;n E/e'<sub>septal</sub> estaban asociados de forma independiente con la funci&#243;n global del VI estimada a trav&#233;s del &#237;ndice Tei (<xref ref-type="table" rid="t4-body3">Tabla 4</xref>).</p>
      <table-wrap id="t3-body3">
        <graphic xlink:href="1678-4170-abc-96-05-0377-00039-gt03-es.jpg"/></table-wrap>
      <table-wrap id="t4-body3">
        <graphic xlink:href="1678-4170-abc-96-05-0377-00039-gt04-es.jpg"/></table-wrap>
      <p>Adem&#225;s de eso, determinamos cuales par&#225;metro estaban asociados con todos los intervalos de tiempo usados en la ecuaci&#243;n del &#237;ndice Tei (TRIV, TCIV y TE).</p>
      <p>El an&#225;lisis univariado de los par&#225;metros cl&#237;nicos y ecocardiogr&#225;ficos en el grupo SM mostr&#243; que la PAS, niveles de glucemia de ayuno, CC, espesor relativa de la pared, di&#225;metro atrial izquierdo, &#237;ndice de masa del VI, raz&#243;n E/A, tiempo de desaceleraci&#243;n (TD), e'<sub>septal</sub> y raz&#243;n E/e'<sub>septal</sub> estaban asociados con el TRIV (<xref ref-type="table" rid="esa05t5-body3">Tabla 5</xref>). Adem&#225;s de eso, todos esos par&#225;metros, excepto el di&#225;metro atrial izquierdo, raz&#243;n E/A y TD, estaban independientemente asociados con el TRIV (<xref ref-type="table" rid="esa05t6-body3">Tabla 6</xref>).</p>
      <p content-type="asset">
        <table-wrap id="esa05t5-body3">
          <graphic xlink:href="1678-4170-abc-96-05-0377-00039-gt05-es.jpg"/></table-wrap>
      </p>
      <p content-type="asset">
        <table-wrap id="esa05t6-body3">
          <graphic xlink:href="1678-4170-abc-96-05-0377-00039-gt06-es.jpg"/></table-wrap>
      </p>
      <p>El an&#225;lisis de correlaci&#243;n mostr&#243; que la PAS, PAD, niveles de glucemia de ayuno, CC, espesor relativo de la pared, di&#225;metro atrial izquierdo, &#237;ndice de masa del VI, raz&#243;n E/A, TD, e'<sub>septal</sub> y raz&#243;n E/e'<sub>septal</sub> estaban asociados con el TCIV (<xref ref-type="table" rid="esa05t5-body3">Tabla 5</xref>). Todos los par&#225;metros mencionados, excepto la PAD, estaban asociados de forma independiente con el TCIV (<xref ref-type="table" rid="esa05t6-body3">Tabla 6</xref>). </p>
      <p>El an&#225;lisis univariado tambi&#233;n demostr&#243; que la PAS, di&#225;metro atrial izquierdo, &#237;ndice de masa del VI, FE, s<sub>septal</sub>, TD, e'<sub>septal</sub> y raz&#243;n E/e'<sub>septal</sub> estaban asociados con el TE (<xref ref-type="table" rid="esa05t5-body3">Tabla 5</xref>). Entre tanto, apenas la PAS, &#237;ndice de masa del VI, FE y s<sub>septal</sub> estaban asociados de forma independiente con el TE (<xref ref-type="table" rid="esa05t6-body3">Tabla 6</xref>).</p>
      <p>El an&#225;lisis de correlaci&#243;n mostr&#243; que todos los componentes de la SM, excepto el HDL-colesterol, estaban asociados con el &#237;ndice Tei, pero apenas la PAS, niveles de glucemia de ayuno y triglic&#233;ridos estaban asociados de forma independiente con ese par&#225;metro de la funci&#243;n global del VI (<xref ref-type="table" rid="t7-body3">Tabla 7</xref>).</p>
      <table-wrap id="t7-body3">
        <graphic xlink:href="1678-4170-abc-96-05-0377-00039-gt07-es.jpg"/></table-wrap>
      <p>
        <bold>Discusi&#243;n</bold>
      </p>
      <p>El &#237;ndice Tei es un par&#225;metro ecocardiogr&#225;fico especial que simult&#225;neamente muestra las funciones sist&#243;lica y diast&#243;lica de un ventr&#237;culo. </p>
      <p>No hay un consenso sobre el impacto de la edad y FC en el &#237;ndice Tei<sup>2,3,5,7,16</sup>. Nuestro estudio mostr&#243; que el &#237;ndice de la funci&#243;n global del VI era independiente de la edad, lo que es muy importante para la evaluaci&#243;n de la funci&#243;n global del VI en pacientes de diferentes edades. Por otro lado, este estudio mostr&#243; que la FC se correlacionaba con el &#237;ndice Tei, aunque no de forma independiente. Resultados similares fueron obtenidos en otros estudios <sup>2,17</sup>. </p>
      <p>La hipertensi&#243;n arterial altera la estructura mioc&#225;rdica, primariamente debido al dep&#243;sito anormal de col&#225;geno en el espacio extracelular, resultando en una disminuci&#243;n de la complacencia y aparici&#243;n de disfunci&#243;n diast&#243;lica del VI<sup>18</sup>. </p>
      <p>No hay un consenso universal sobre la influencia de la PAS y de la PAD en la funci&#243;n ventricular global del VI y el &#237;ndice Tei. Algunos autores mostraron que el &#237;ndice Tei se correlaciona con la presi&#243;n arterial<sup>5,15,19</sup>, mientras que otros no concuerdan<sup>2,17</sup>. Nuestro estudio mostr&#243; que la PAS y la PAD se correlacionaron con el &#237;ndice de desempe&#241;o mioc&#225;rdico, pero apenas la PAS estaba asociada de forma independiente con el &#237;ndice Tei. El mismo resultado fue obtenido cuando consideramos apenas los criterios del SM. Adem&#225;s de eso, la PAS mostr&#243; ser el predictor independiente m&#225;s fuerte del &#237;ndice Tei entre los criterios del SM con mayor significaci&#243;n estad&#237;stica (p &lt; 0,001).</p>
      <p>La resistencia a la insulina subyacente a la diabetes mellitus tipo 2 y SM lleva a alteraciones significativos en la estructura y funci&#243;n del VI. B&#225;sicamente, lleva a la activaci&#243;n del sistema nervioso simp&#225;tico y del sistema renina-angiotensina-aldosterona (SRAA), causando reducci&#243;n en el n&#250;mero de mitocondrias, elementos contr&#225;ctiles, densidad de la red capilar, e induce fibrosis extracelular y apoptose<sup>20</sup>. Todas esas alteraciones resultan en la aparici&#243;n de disfunci&#243;n diast&#243;lica del VI y, subsecuentemente, hipertrofia del VI. Pattoneri et al<sup>3</sup> mostraron que individuos recientemente diagnosticados con diabetes mellitus tipo 2 presentaban funci&#243;n global del VI anormal. Hay un dilema en relaci&#243;n a si los niveles de glucosa y hemoglobina glicada afectan o no la funci&#243;n global del VI. Estudios han confirmado que esa relaci&#243;n existe<sup>3,5,19</sup>, lo que tambi&#233;n fue el resultado de nuestro estudio. El an&#225;lisis separado de la influencia de los componentes del SM en nuestro estudio tambi&#233;n demostr&#243; que los niveles de glucemia de ayuno, adem&#225;s de la PAS y niveles de triglic&#233;ridos, estaban asociados de forma independiente con el &#237;ndice Tei. </p>
      <p>Los estudios que investigaron los efectos individuales y simult&#225;neos de la hipertensi&#243;n y diabetes en la funci&#243;n global del VI no llegaron a un acuerdo sobre si esos factores sin&#233;rgicamente llevan a mayor da&#241;o en el VI. Cho et al<sup>21</sup> mostraron que los efectos simult&#225;neos de esos factores alteraban la funci&#243;n global del VI m&#225;s que los factores individuales separadamente. Otros autores no concuerdan y creen que las diferencias entre los efectos individuales y simult&#225;neos de esos dos factores no existen<sup>3,17</sup>.</p>
      <p>No hay consenso absoluto sobre el impacto de la obesidad en el &#237;ndice Tei. Levent et al<sup>4</sup> estudiaron el efecto de la hipertensi&#243;n y obesidad en ni&#241;os y mostr&#243; que ni&#241;os obesos, pero normotensos, ten&#237;an un &#237;ndice Tei m&#225;s alto, cuando fueron comparados al grupo control, lo que confirmaba da&#241;o a la funci&#243;n global del VI, mientras que ni&#241;os con ambos factores de riesgo presentaban un nivel aun mayor de disfunci&#243;n, lo que indicaba un posible efecto sin&#233;rgico de esos factores. El estudio en una poblaci&#243;n adulta confirm&#243; que la obesidad perjudicaba la funci&#243;n mioc&#225;rdica global por la disminuci&#243;n del &#237;ndice Tei, esto es, mostrando la mejora en la funci&#243;n mioc&#225;rdica con la reducci&#243;n del peso<sup>22</sup>. Hay un estudio controvertido que mostr&#243; que la obesidad no empeoraba, pero s&#237; mejoraba la funci&#243;n global del VI<sup>23</sup>. Entre tanto, los autores no sugirieron posibles mecanismos para ese efecto "protector" del aumento del peso corporal. Nuestro estudio mostr&#243; que el IMC no se correlacionaba con &#237;ndice Tei, en contraste con la CC, que era un predictor independiente de la funci&#243;n global del VI. Esos hallazgos eran esperados, pues no hab&#237;a diferencia significativa en el IMC entre los grupos SM y control, mientras que la CC era significativamente mayor en los individuos con SM. Voulgari et al<sup>19</sup> obtuvieron resultados similares. </p>
      <p>En ese estudio, mostramos que los niveles de LDL y HDL-colesterol no se correlacionaban con el &#237;ndice Tei, mientras que los niveles de colesterol total y triglic&#233;ridos se correlacionaban con ese par&#225;metro. Los niveles de triglic&#233;ridos no se asociaban de forma independiente con el &#237;ndice Tei, cuando todos los par&#225;metros cl&#237;nicos y ecocardiogr&#225;ficos eran considerados. Entre tanto, cuando solamente los criterios de la SM eran considerados, los niveles de triglic&#233;ridos se asociaban de forma independiente con ese &#237;ndice, lo que est&#225; de acuerdo con los hallazgos de otros autores<sup>5,19</sup>. de las Fuentes et al<sup>4</sup> fueron los primeros que mostraron que individuos con niveles de triglic&#233;ridos (TG) aumentados presentaban funci&#243;n diast&#243;lica del VI significativamente deficiente y aumento de la masa del VI, cuando fueron comparados al grupo control. Eso puede ser explicado por el hecho de que los TG acumulados en el espacio extracelular reducen la complacencia del VI, teniendo como consecuencia sus efectos lipot&#243;xicos en los cardiomiocitos y alto consumo de energ&#237;a, que es necesario para su metabolismo. </p>
      <p>Nuestro estudio tambi&#233;n mostr&#243; que la funci&#243;n renal estimada a trav&#233;s de la creatinina s&#233;rica estaba elevada en individuos con SM y se correlacionaba con el &#237;ndice Tei, lo que est&#225; de acuerdo con algunos autores<sup>25</sup>, pero es contradictorio para otros<sup>26</sup>. Entre tanto, la creatinina s&#233;rica no estaba asociada de forma independiente con el &#237;ndice Tei. </p>
      <p>La relaci&#243;n entre varios par&#225;metros ecocardiogr&#225;ficos y el &#237;ndice Tei fue evaluada en pacientes con hipertensi&#243;n, diabetes o aquellos que presentaban ambos factores de riesgo<sup>2,3,17</sup>; entre tanto, esa evaluaci&#243;n no hab&#237;a aun sido realizada en individuos con SM. La mayor&#237;a de los autores cree que la funci&#243;n global del VI deficiente en el SM es en verdad una consecuencia del da&#241;o a la funci&#243;n diast&#243;lica<sup>5,6,19</sup>, que es, en su mayor parte, el resultado de la identificaci&#243;n de la funci&#243;n sist&#243;lica del VI realizada apenas con la fracci&#243;n de eyecci&#243;n sist&#243;lica y/o el acortamiento fraccional del VI. Entre tanto, hay estudios mostrando que esos par&#225;metros tambi&#233;n podr&#237;an estar alterados en individuos con SM<sup>26</sup>. El estudio de imagen por Doppler tisular introdujo nuevos par&#225;metros de la funci&#243;n sist&#243;lica del VI, que mostr&#243; estar deficiente en el grupo con SM<sup>27</sup>. Nuestro estudio mostr&#243; que la funci&#243;n sist&#243;lica del VI estimada a trav&#233;s de la FE y s<sub>septal</sub> estaba preservada en el grupo con SM, aunque con significaci&#243;n estad&#237;stica lim&#237;trofe. </p>
      <p>Todos los par&#225;metros de la funci&#243;n diast&#243;lica del VI evaluados en nuestro estudio (E/A, TD, e'<sub>septal</sub> y raz&#243;n E/e'<sub>septal</sub>) confirmaron la existencia de disfunci&#243;n diast&#243;lica. El espesor relativo de la pared y el &#237;ndice de masa del VI, el di&#225;metro atrial izquierdo, la raz&#243;n E/A, s<sub>septal</sub>, e'<sub>septal</sub> y la raz&#243;n E/e'<sub> septal</sub> se correlacionaron con la funci&#243;n global del VI estimada a trav&#233;s del &#237;ndice Tei; entre tanto, el &#237;ndice de masa del VI, e'<sub>septal</sub> y raz&#243;n E/e'<sub>septal</sub> estaban asociados de forma independiente con el &#237;ndice Tei. Resultados similares fueron obtenidos por Masugata et al<sup>2</sup> en pacientes con hipertensi&#243;n. Andersen et al<sup>17</sup> descubrieron una correlaci&#243;n entre el &#237;ndice Tei y el TD y la raz&#243;n E/A ratio en pacientes con hipertensi&#243;n y diabetes, mientras que Pattoneri et al<sup>3</sup> encontraron una correlaci&#243;n entre el TCIV y el TE con ese &#237;ndice en pacientes con diabetes de diagn&#243;stico reciente. </p>
      <p>Adem&#225;s de eso, estudiamos el impacto de diferentes par&#225;metros cl&#237;nicos y ecocardiogr&#225;ficos en el grupo SM sobre los intervalos del Doppler tisular necesarios para el c&#225;lculo del &#237;ndice Tei (TRIV, TCIV y TE). La PAS, glucemia de ayuno, CC, espesor relativo de la pared, &#237;ndice de masa del VI, e'<sub>septal</sub> y raz&#243;n E/e'<sub>septal</sub> estaban asociados de forma independiente con el TRIV. El an&#225;lisis multivariado mostr&#243; que la PAS, PAD, glucemia de ayuno, &#237;ndice de masa del VI, e'<sub>septal</sub> y raz&#243;n E/e'<sub>septal</sub> estaban asociados de forma independiente con el TCIV. Esos par&#225;metros representan, simult&#225;neamente, las funciones sist&#243;lica y diast&#243;lica del VI en la ecuaci&#243;n del &#237;ndice de Tei. Por otro lado, el TE, un par&#225;metro de la funci&#243;n sist&#243;lica en esa ecuaci&#243;n, estaba asociado de forma independiente con la PAS, &#237;ndice de masa del VI, FE y s<sub>septal</sub>. Aparentemente, casi los mismos factores que est&#225;n asociados con TRIV, TCIV y TE en la SM se correlacionaron con el &#237;ndice Tei como par&#225;metro de la funci&#243;n global del VI. Esos hallazgos son importantes, pues demostramos que no es necesario determinar factores de riesgo para componentes individuales del &#237;ndice Tei. </p>
      <p>Considerando que la funci&#243;n sist&#243;lica del VI estaba preservada en individuos con SM en nuestro estudio, mientras que, por otro lado, la funci&#243;n diast&#243;lica estaba deficiente, la conclusi&#243;n l&#243;gica es que el da&#241;o a la funci&#243;n global del VI es en verdad el resultado de alteraciones en la funci&#243;n diast&#243;lica. Entre tanto, un grupo de estudio mayor posiblemente habr&#237;a demostrado que la funci&#243;n sist&#243;lica del VI tambi&#233;n estaba alterada en individuos con SM, considerando que el valor estad&#237;stico en nuestro estudio fue lim&#237;trofe (p = 0,075).</p>
      <p>La limitaci&#243;n del presente estudio consisti&#243; en un gran n&#250;mero de individuos con SM e hipertensi&#243;n arterial, que era controlada a trav&#233;s del uso de diferentes medicamentos que podr&#237;an afectar el &#237;ndice Tei y la interpretaci&#243;n de los resultados. Otra limitaci&#243;n es el hecho de que pocos estudios cl&#237;nicos utilizaron la imagen del Doppler tisular para obtener par&#225;metros de funci&#243;n sist&#243;lica, diast&#243;lica y global del VI; siendo as&#237;, no pudimos realizar una comparaci&#243;n completa de esos par&#225;metros. Estudios diagn&#243;sticos demostraron que el &#237;ndice Tei obtenido por Doppler pulsado y tisular presentaban valores similares y aunque haya sido demostrado que los valores determinados por el Doppler tisular son m&#225;s precisos y presentan mejor correlaci&#243;n con las medidas invasivas obtenidas durante la cateterizaci&#243;n card&#237;aca, la comparaci&#243;n es bastante razonable<sup>28</sup>. La tercera limitaci&#243;n es relativa a la dependencia de la precarga que el &#237;ndice Tei presenta<sup>29</sup>.</p>
      <p>
        <bold>Conclusi&#243;n</bold>
      </p>
      <p>El s&#237;ndrome metab&#243;lico lleva al da&#241;o card&#237;aco subcl&#237;nico, reduciendo la funci&#243;n global del VI. El &#237;ndice Tei es una manera relativamente simple de estimar la funci&#243;n global del VI y por lo tanto, un par&#225;metro valioso en la pr&#225;ctica cl&#237;nica de rutina. El an&#225;lisis de regresi&#243;n m&#250;ltiple de los par&#225;metros cl&#237;nicos mostr&#243; que la PAS, glucemia de ayuno, &#237;ndice de masa del VI, raz&#243;n E/e'<sub>septal</sub>, y e'<sub>septal</sub> estaban asociados de forma independiente con la funci&#243;n global del VI estimada a trav&#233;s del &#237;ndice Tei. Tambi&#233;n demostramos que casi los mismos factores que est&#225;n asociados con el TRIV, TCIV y TE en el grupo con SM tambi&#233;n est&#225;n asociados con el &#237;ndice Tei. La funci&#243;n diast&#243;lica deficiente del VI es la principal raz&#243;n del deterioro de la funci&#243;n global del VI en el SM, de acuerdo con nuestro estudio. </p>
      <p>Adem&#225;s de eso, mostramos que, entre los componentes del SM, apenas la presi&#243;n arterial sist&#243;lica, glucemia de ayuno y niveles de triglic&#233;ridos estaban asociados de forma independiente con la funci&#243;n global del ventr&#237;culo izquierdo.</p>
      <p>
        <bold>Potencial Conflicto de Intereses</bold>
      </p>
      <p>Declaro no haber conflicto de intereses pertinentes.</p>
      <p>
        <bold>Fuentes de Financiaci&#243;n</bold>
      </p>
      <p>El presente estudio no tuve fuentes de financiaci&#243;n externas.</p>
      <p>
        <bold>Vinculaci&#243;n Acad&#233;mica</bold>
      </p>
      <p>No hay vinculaci&#243;n de este estudio a programas de postgrado.</p>
      <p>
        <bold>Referencias</bold>
      </p>
    </body>
  </sub-article>
</article>
