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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introdu&#231;&#227;o</span><p id="par0065" class="elsevierStylePara elsevierViewall">As doen&#231;as cardiovasculares s&#227;o ainda a principal causa de morte na Europa e Portugal n&#227;o &#233; exce&#231;&#227;o&#44; apesar do decr&#233;scimo progressivo que se tem verificado nas &#250;ltimas d&#233;cadas<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">1&#8211;3</span></a>&#46; Este facto observa&#8208;se na popula&#231;&#227;o geral&#44; mas em 2015 os tumores malignos j&#225; ultrapassam as doen&#231;as do aparelho circulat&#243;rio como principal causa de morte no sexo masculino<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">3</span></a>&#46; Para al&#233;m dos fatores de risco cardiovasculares j&#225; bem estabelecidos&#44; como a hipertens&#227;o arterial &#40;HTA&#41;&#44; o tabagismo&#44; a diabetes&#44; a eleva&#231;&#227;o do colesterol&#8208;LDL&#44; a idade e a hist&#243;ria familiar&#44; diversos outros fatores de risco t&#234;m vindo a ser valorizados nos &#250;ltimos anos&#46; Em particular&#44; a s&#237;ndrome metab&#243;lica &#40;SM&#41;&#44; uma agrega&#231;&#227;o de diversos fatores de risco&#44; pela sua elevada preval&#234;ncia a n&#237;vel mundial&#44; atingindo um padr&#227;o quase epid&#233;mico e pela associa&#231;&#227;o j&#225; demonstrada ao desenvolvimento de diabetes tipo 2 e doen&#231;as cardiovasculares &#40;num risco que pode ser at&#233; duas vezes superior&#41;&#44; tem sido um problema importante&#44; agravado pelo facto de o seu tratamento depender de uma profunda altera&#231;&#227;o dos estilos de vida&#44; muitas vezes dif&#237;ceis de implementar na popula&#231;&#227;o geral<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">4&#8211;6</span></a>&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Diversas meta&#8208;an&#225;lises pr&#233;vias demonstraram claramente que em preven&#231;&#227;o prim&#225;ria existe uma associa&#231;&#227;o clara entre a presen&#231;a de SM e a ocorr&#234;ncia de eventos cardiovasculares no seguimento<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">4&#8211;7</span></a>&#46; O mesmo foi demonstrado no estudo VALSIM realizado numa popula&#231;&#227;o portuguesa<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">8</span></a>&#46; Em preven&#231;&#227;o secund&#225;ria&#44; os resultados s&#227;o contradit&#243;rios&#44; com alguns estudos mostrando efeito neutro e outros maior incid&#234;ncia de eventos cardiovasculares&#44; mas com seguimentos inferiores a tr&#234;s anos<a class="elsevierStyleCrossRefs" href="#bib0195"><span class="elsevierStyleSup">9&#44;10</span></a>&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Em trabalhos pr&#233;vios&#44; demonstr&#225;mos que a presen&#231;a de SM <span class="elsevierStyleItalic">per se</span> n&#227;o se associa &#224; presen&#231;a de aterosclerose subcl&#237;nica &#40;avaliada pela espessura &#237;ntima&#8208;m&#233;dia da car&#243;tida comum &#8211; EIMc&#41; mas que alguns dos componentes desta s&#237;ndrome&#44; nomeadamente a hiperinsulin&#233;mia&#44; hiperglicemia e os n&#237;veis baixos do colesterol&#8208;HDL&#44; est&#227;o diretamente associados&#44; demostrando o efeito heterog&#233;neo dos diversos componentes da entidade SM<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">11&#8211;13</span></a>&#46; Do mesmo modo&#44; tamb&#233;m n&#227;o se constatou rela&#231;&#227;o direta com a presen&#231;a de doen&#231;a coron&#225;ria angiograficamente significativa &#40;avaliada em contexto est&#225;vel&#41;&#44; sendo a hiperglicemia e a hipertriglicerid&#233;mia os componentes preditores de presen&#231;a de doen&#231;a coron&#225;ria<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">14</span></a>&#46; Em ambos os estudos&#44; o per&#237;metro abdominal mostrou um efeito paradoxal&#44; protetor<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">12&#44;14</span></a>&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Estes trabalhos iniciais tiveram origem num estudo transversal e observacional&#46; Passados mais de cinco anos desde esta an&#225;lise&#44; temos como presente objetivo analisar o mesmo grupo de doentes e verificar num seguimento a longo&#8208;prazo &#40;superior a cinco anos&#41; se a presen&#231;a de SM se associa a maior ocorr&#234;ncia de mortalidade ou maior incid&#234;ncia de eventos cerebrais ou cardiovasculares&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">M&#233;todos</span><p id="par0085" class="elsevierStylePara elsevierViewall">Inclu&#237;ram&#8208;se no trabalho original indiv&#237;duos adultos &#40;&#8805; 18 anos&#41; admitidos eletivamente para realiza&#231;&#227;o de coronariografia por suspeita de doen&#231;a coron&#225;ria &#40;por queixas de angor e&#47;ou isquemia documentada por testes n&#227;o invasivos&#41; entre 2008 e 2010&#46; Foram exclu&#237;dos doentes com antecedentes de s&#237;ndrome coron&#225;ria aguda&#44; revasculariza&#231;&#227;o mioc&#225;rdica pr&#233;via ou doen&#231;a coron&#225;ria conhecida&#44; doen&#231;a valvular significativa&#44; cardiopatia cong&#233;nita ou outras miocardiopatias&#46; Nos trabalhos originais&#44; foi utilizada a defini&#231;&#227;o de SM da <span class="elsevierStyleItalic">American Heart Association&#47;National Heart Lung and Blood Institute</span><a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">15</span></a>&#46; Contudo&#44; presentemente&#44; a defini&#231;&#227;o foi harmonizada pelas diversas sociedades cient&#237;ficas&#44; sendo a principal diferen&#231;a a possibilidade de cada pa&#237;s&#47;regi&#227;o poder definir os limites de obesidade abdominal tendo em conta padr&#245;es &#233;tnicos<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">16</span></a>&#46; Utiliz&#225;mos ent&#227;o a nova defini&#231;&#227;o e consider&#225;mos os limites anteriormente definidos para o per&#237;metro abdominal &#40;&#8805; 88<span class="elsevierStyleHsp" style=""></span>cm para as mulheres e &#8805; 102<span class="elsevierStyleHsp" style=""></span>cm para os homens&#41;&#46; Os outros crit&#233;rios s&#227;o uma press&#227;o arterial &#8805; 130&#47;85<span class="elsevierStyleHsp" style=""></span>mmHg &#40;ou sob terap&#234;utica especifica&#41;&#44; colesterol&#8208;HDL &#8804; 40<span class="elsevierStyleHsp" style=""></span>mg&#47;dL nos homens ou &#8804; 50<span class="elsevierStyleHsp" style=""></span>mg&#47;dL nas mulheres &#40;ou sob terap&#234;utica especifica&#41;&#44; triglic&#233;ridos &#8805; 150<span class="elsevierStyleHsp" style=""></span>mg&#47;dL &#40;ou sob terap&#234;utica especifica&#41; e glicemia &#8805; 100<span class="elsevierStyleHsp" style=""></span>mg&#47;dL &#40;ou sob terap&#234;utica espec&#237;fica&#41;<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">15&#44;16</span></a>&#46; A SM &#233; definida pela presen&#231;a de pelo menos tr&#234;s dos crit&#233;rios referidos&#46; A presen&#231;a de doen&#231;a coron&#225;ria angiograficamente significativa foi definida pela presen&#231;a de estenose &#8805; 70&#37; em qualquer vaso coron&#225;rio epic&#225;rdico&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">Em todos os doentes&#44; a informa&#231;&#227;o de seguimento foi obtida por entrevista telef&#243;nica com o doente ou com familiares diretos aos 30 dias e ao primeiro ano ap&#243;s o internamento por uma equipa especialmente dedicada &#224; colheita de dados de seguimento dos doentes internados no servi&#231;o&#46; Em 2017&#44; realizou&#8208;se novo contacto para obter informa&#231;&#227;o adicional de seguimento desta coorte espec&#237;fica&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Foram considerados e analisados v&#225;rios eventos no seguimento&#46; A mortalidade de todas as causas define&#8208;se como morte por qualquer motivo&#46; A mortalidade de causa cardiovascular define&#8208;se como morte associada a patologia cardiovascular&#46; S&#237;ndrome coron&#225;ria aguda foi definida pela presen&#231;a de angor em repouso &#40;ou equivalente de angor&#41; com altera&#231;&#245;es no ECG e&#47;ou subida&#47;descida de marcadores de necrose mioc&#225;rdica&#46; Quando foi realizada angioplastia coron&#225;ria ou cirurgia de revasculariza&#231;&#227;o mioc&#225;rdica durante o seguimento&#44; sem rela&#231;&#227;o com o motivo de internamento inicial&#44; considerou&#8208;se a ocorr&#234;ncia de revasculariza&#231;&#227;o mioc&#225;rdica&#46; Internamento por insufici&#234;ncia card&#237;aca definiu&#8208;se como internamento por aparecimento&#47;agravamento de sintomas ou sinais de insufici&#234;ncia card&#237;aca&#46; Readmiss&#227;o cardiovascular foi considerada sempre que o doente foi internado por motivo cardiovascular agudo ou eletivo&#46; Acidente vascular cerebral &#40;AVC&#41;&#47;acidente isqu&#233;mico transit&#243;rio &#40;AIT&#41; foi definido pela presen&#231;a de instala&#231;&#227;o de novo de d&#233;ficits neurol&#243;gicos&#46; Foi tamb&#233;m analisado um composto de v&#225;rios eventos card&#237;acos e cerebrais &#40;mortalidade de todas as causas&#44; s&#237;ndrome coron&#225;ria aguda&#44; revasculariza&#231;&#227;o mioc&#225;rdica&#44; AVC&#47;AIT ou admiss&#227;o por insufici&#234;ncia card&#237;aca&#41;&#46; Nos doentes com eventos&#44; foi realizada an&#225;lise do processo cl&#237;nico para confirma&#231;&#227;o e classifica&#231;&#227;o adequada do evento ou foi solicitado ao doente informa&#231;&#227;o adicional&#46; Efetuou&#8208;se compara&#231;&#227;o destes eventos em doentes com e sem doen&#231;a coron&#225;ria&#44; bem como em doentes com e sem SM&#44; dividindo assim os indiv&#237;duos por quatro grupos&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">Todos os indiv&#237;duos assinaram consentimento informado para a participa&#231;&#227;o no estudo e o presente trabalho est&#225; de acordo com a Declara&#231;&#227;o de Helsinquia&#46;</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">An&#225;lise estat&#237;stica</span><p id="par0105" class="elsevierStylePara elsevierViewall">As vari&#225;veis cont&#237;nuas est&#227;o reportadas como m&#233;dia e desvio&#8208;padr&#227;o&#46; Foi testada a normalidade com recurso ao teste de Kolmogorov&#8208;Smirnov&#46; A compara&#231;&#227;o das vari&#225;veis cont&#237;nuas foi efetuada pelo teste ANOVA&#46; As vari&#225;veis categ&#243;ricas est&#227;o descritas como percentagens e foram comparadas com o teste qui&#8208;quadrado ou o teste de Fischer&#44; conforme apropriado&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">As estimativas de sobreviv&#234;ncia livre de eventos no seguimento foram calculadas pelo m&#233;todo de Kaplan&#8208;Meier e as curvas foram comparadas pelo teste <span class="elsevierStyleItalic">Log&#8208;rank</span>&#46; Foi utilizada a an&#225;lise de Cox <span class="elsevierStyleItalic">proportional&#8208;hazards</span> para analisar a influ&#234;ncia da presen&#231;a de SM e de doen&#231;a coron&#225;ria angiograficamente significativa na ocorr&#234;ncia de eventos a longo prazo e ajustada para as vari&#225;veis com impacto significativo no progn&#243;stico&#46; As estimativas de associa&#231;&#227;o entre os preditores e os eventos est&#227;o apresentadas como <span class="elsevierStyleItalic">Hazard Ratios</span> &#40;HR&#41; e intervalo de confian&#231;a de 95&#37;&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">Foi utilizado o programa IBM SPSS <span class="elsevierStyleItalic">statistical software package</span> &#40;vers&#227;o 19&#46;0&#46;0&#46;2&#41; e considerado um valor de p inferior a 0&#44;05 como estatisticamente significativo&#46;</p></span></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Resultados</span><p id="par0120" class="elsevierStylePara elsevierViewall">Foram inclu&#237;dos no estudo inicial 300 doentes&#44; tendo quatro doentes sido perdidos no seguimento&#46; Dos 296 doentes inclu&#237;dos na presente an&#225;lise&#44; 59&#37; s&#227;o do sexo masculino&#44; com idade m&#233;dia de 65 &#177; 9 anos &#40;38&#8208;86 anos&#41;&#46; A preval&#234;ncia de SM &#233; de 55&#44;7&#37; e o componente mais prevalente de SM foi a HTA&#44; seguido pela obesidade abdominal&#44; glicemia elevada&#44; colesterol&#8208;HDL baixo e triglic&#233;ridos elevados &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">tabela 1</a>&#41;&#46; Em apenas 41&#44;6&#37; dos indiv&#237;duos se detetou a presen&#231;a de doen&#231;a coron&#225;ria angiograficamente significativa&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0125" class="elsevierStylePara elsevierViewall">Num seguimento m&#233;dio de 6&#44;9 &#177; 2&#44;2 anos&#44; ocorreram 10&#44;1&#37; de mortes de todas as causas&#44; 3&#44;7&#37; de mortes cardiovasculares&#44; 14&#44;2&#37; de admiss&#245;es de causa cardiovascular e 22&#44;0&#37; de eventos compostos &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">tabela 2</a>&#41;&#46; N&#227;o se verificaram diferen&#231;as estatisticamente significativas em termos de mortalidade de todas as causas ou cardiovasculares comparando todos os grupos &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">tabela 2</a> e <a class="elsevierStyleCrossRefs" href="#fig0005">figuras 1 e 2</a>&#41;&#46; Pelo contr&#225;rio&#44; os reinternamentos de causa cardiovascular e os eventos compostos foram mais frequentes nos grupos com doen&#231;a coron&#225;ria &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">tabela 2</a> e <a class="elsevierStyleCrossRefs" href="#fig0015">figuras 3 e 4</a>&#41;&#46; Esta diferen&#231;a foi particularmente condicionada por maior ocorr&#234;ncia de s&#237;ndrome coron&#225;ria aguda no grupo com SM e DC &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">tabela 2</a>&#41;&#46; Ambos os grupos de DC mostram maior realiza&#231;&#227;o de ICP e readmiss&#227;o cardiovascular &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">tabela 2</a>&#41;&#46; A DC associou&#8208;se a mais eventos&#46; Com efeito&#44; nos indiv&#237;duos sem SM&#44; as readmiss&#245;es cardiovasculares e os eventos compostos foram significativamente mais frequentes na presen&#231;a de doen&#231;a coron&#225;ria &#40;<span class="elsevierStyleItalic">Log&#8208;rank</span>&#44; p &#61; 0&#44;001 e p &#61; 0&#44;004&#44; respetivamente&#41;&#44; verificando&#8208;se o mesmo nos indiv&#237;duos com SM &#40;<span class="elsevierStyleItalic">Log&#8208;rank</span>&#44; p &#61; 0&#44;007 e p &#61; 0&#44;002&#44; respetivamente&#41;&#46; Na presen&#231;a de doen&#231;a coron&#225;ria&#44; verificou&#8208;se que a presen&#231;a concomitante de SM se associou a uma tend&#234;ncia para maior morte de todas as causas &#40;<span class="elsevierStyleItalic">Log&#8208;rank</span>&#44; p &#61; 0&#44;382&#41; e para os eventos compostos &#40;<span class="elsevierStyleItalic">Log&#8208;rank</span>&#44; p &#61; 0&#44;365&#41; &#40;<a class="elsevierStyleCrossRefs" href="#fig0005">figuras 1 e 4</a>&#41;&#46; Tamb&#233;m se verifica maior ocorr&#234;ncia de s&#237;ndrome coron&#225;ria aguda&#44; embora sem atingir significado estat&#237;stico &#40;<span class="elsevierStyleItalic">Log&#8208;rank</span>&#44; p &#61; 0&#44;094&#41; mas com uma clara tend&#234;ncia para mais eventos&#46; Os grupos com SM tiveram menos internamentos por insufici&#234;ncia card&#237;aca&#46; A incid&#234;ncia de neoplasias foi semelhante na presen&#231;a ou aus&#234;ncia de SM&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia><p id="par0130" class="elsevierStylePara elsevierViewall">Em an&#225;lise multivariada&#44; apenas a presen&#231;a de doen&#231;a coron&#225;ria foi preditora independente de internamento cardiovascular e eventos compostos&#44; mas n&#227;o de mortalidade &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">tabela 3</a>&#41;&#46; A SM n&#227;o foi preditora independente de nenhum dos eventos considerados&#46; A idade foi preditora independente de morte de todas as causas &#40;HR 1&#44;1&#44; p &#60; 0&#44;001&#41;&#44; morte cardiovascular &#40;HR 1&#44;13&#44; p &#61; 0&#44;002&#41;&#44; reinternamento cardiovascular &#40;HR 1&#44;05&#44; p &#61; 0&#44;020&#41; e eventos compostos &#40;HR 1&#44;07&#44; p &#60; 0&#44;001&#41;&#46; A diabetes foi preditora independente de morte de todas as causas &#40;HR 3&#44;11&#44; p &#61; 0&#44;004&#41; e eventos compostos &#40;HR 1&#44;97&#44; p &#61; 0&#44;012&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Discuss&#227;o</span><p id="par0135" class="elsevierStylePara elsevierViewall">Em meta&#8208;an&#225;lises pr&#233;vias &#40;em doentes na sua maioria em preven&#231;&#227;o prim&#225;ria&#41; foi demonstrada a associa&#231;&#227;o entre SM e eventos cardiovasculares<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">4&#8211;7</span></a>&#46; Esta associa&#231;&#227;o manteve&#8208;se mesmo ap&#243;s ajuste para outros fatores de risco&#44; o que corrobora a exist&#234;ncia de um fen&#243;meno de potencia&#231;&#227;o de risco e relev&#226;ncia epidemiol&#243;gica&#46; Com efeito&#44; a presen&#231;a de SM associou&#8208;se a um aumento de duas vezes do risco de doen&#231;a cardiovascular&#44; mortalidade cardiovascular&#44; enfarte do mioc&#225;rdio e acidente vascular cerebral e aumento de 1&#44;5 vezes no risco de mortalidade total<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">6</span></a>&#46; Assim&#44; os doentes com SM apresentam maior risco para eventos cardiovasculares do que para mortalidade total&#46; Mesmo na aus&#234;ncia de diabetes <span class="elsevierStyleItalic">mellitus</span>&#44; a presen&#231;a de SM associou&#8208;se a aumento de risco de mortalidade cardiovascular&#44; enfarte mioc&#225;rdio e AVC&#44; n&#227;o sendo&#44; contudo&#44; significativo para a mortalidade total<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">6</span></a>&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">Em Portugal&#44; no estudo VALSIM&#44; a SM associou&#8208;se de forma independente &#224; presen&#231;a de doen&#231;a coron&#225;ria &#40;definida como angina e&#47;ou hist&#243;ria pr&#233;via de enfarte do mioc&#225;rdio&#41; e particularmente &#224; presen&#231;a de diabetes&#44; confirmando a sua relev&#226;ncia cl&#237;nica na ocorr&#234;ncia de doen&#231;a cardiovascular em Portugal<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">8</span></a>&#46; A hipertens&#227;o &#233; o componente de SM que se associou de forma mais potente com a ocorr&#234;ncia de doen&#231;a cardiovascular&#44; tendo&#8208;se&#44; contudo&#44; destacado tamb&#233;m com alguma relev&#226;ncia a eleva&#231;&#227;o da glicemia&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">Os estudos em preven&#231;&#227;o secund&#225;ria t&#234;m mostrado resultados contradit&#243;rios&#44; com alguns a mostrar impacto na ocorr&#234;ncia de eventos e outros com efeito neutro&#44; mas na sua maioria n&#227;o ultrapassando os 36 meses de seguimento<a class="elsevierStyleCrossRefs" href="#bib0195"><span class="elsevierStyleSup">9&#44;10</span></a>&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">Um estudo com ecografia intracoron&#225;ria mostrou que nos indiv&#237;duos com SM existe uma alta preval&#234;ncia de placas com elevado conte&#250;do lip&#237;dico&#44; mais inst&#225;veis&#44; sendo a SM fator preditor independente deste tipo de placas<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">17&#44;18</span></a>&#46; Contudo&#44; em preven&#231;&#227;o secund&#225;ria&#44; o refor&#231;o da terap&#234;utica farmacol&#243;gica&#44; nomeadamente as estatinas&#44; t&#234;m impacto conhecido na redu&#231;&#227;o de eventos por estabiliza&#231;&#227;o das placas ateroscler&#243;ticas&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">Por outro lado&#44; a SM &#233; uma entidade muito heterog&#233;nea&#44; dependendo do tipo de agrega&#231;&#227;o de fatores de risco&#46; No estudo MESYAS realizado em Espanha&#44; o risco de doen&#231;a cardiovascular &#233; vari&#225;vel consoante o componente analisado&#44; com alguns componentes isolados de SM a conferirem diferentes intensidades de risco<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">19</span></a>&#46; Com efeito&#44; o risco associado a SM &#233; plenamente explicado pelos seus componentes considerados individualmente&#46; A hipertriglicerid&#233;mia foi o componente que conferiu maior risco&#46; Pelo contr&#225;rio&#44; a obesidade &#40;avaliada pelo IMC&#41; n&#227;o foi um fator independente de risco para doen&#231;a cardiovascular&#44; parecendo mesmo ser protetor&#46; A sobrecarga cardiovascular associada &#224; obesidade parece assim ser condicionada principalmente pelo aparecimento de outros fatores de risco metab&#243;licos como a hiperglicemia&#44; dislipid&#233;mia aterog&#233;nica e a hipertens&#227;o&#46; Tendo em conta que a SM resulta de uma agrega&#231;&#227;o de pelo menos tr&#234;s fatores de risco&#44; temos como consequ&#234;ncia a exist&#234;ncia de uma grande heterogeneidade de risco entre os doentes com SM dependente dos crit&#233;rios utilizados para o diagn&#243;stico&#46; Na presen&#231;a de obesidade&#44; &#233; necess&#225;ria a presen&#231;a de apenas outros dois fatores de risco&#46; Contudo&#44; na aus&#234;ncia de obesidade&#44; s&#227;o necess&#225;rios outros tr&#234;s componentes que apresentam um risco cardiovascular muito mais significativo&#46; Assim&#44; o tipo de componentes agregados poder&#225; ser importante para o desenvolvimento de doen&#231;a coron&#225;ria&#44; em particular se estiverem envolvidos em simult&#226;neo a eleva&#231;&#227;o da glicemia e dislipid&#233;mia aterog&#233;nica&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">Com efeito&#44; estudos longitudinais encontraram uma incid&#234;ncia de eventos cardiovasculares id&#234;ntica entre obesos metabolicamente benignos &#40;definidos pela aus&#234;ncia de s&#237;ndrome metab&#243;lico e diabetes&#41; e indiv&#237;duos com peso normal&#44; em contraste com o elevado risco cardiovascular em indiv&#237;duos obesos de alto risco&#44; com agrega&#231;&#227;o de fatores de risco cardiometab&#243;licos<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">20</span></a>&#46; Uma an&#225;lise dos dados de tr&#234;s grandes estudos &#40;<span class="elsevierStyleItalic">Framingham Offspring Study&#44; Atherosclerosis Risk In Communities</span> e <span class="elsevierStyleItalic">Cardiovascular Health Study</span>&#41; mostrou que a presen&#231;a de componentes de SM&#44; de SM propriamente dito ou de diabetes associa&#8208;se a um aumento de duas a cinco vezes do risco de eventos coron&#225;rios ou AVC num seguimento m&#233;dio de oito anos&#44; mesmo tendo em conta a obesidade abdominal<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">21</span></a>&#44; sugerindo que a presen&#231;a de anomalias metab&#243;licas &#233; um fator preditor substancialmente mais forte do que a obesidade abdominal na incid&#234;ncia de eventos cardiovasculares&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">Quando existe doen&#231;a coron&#225;ria estabelecida&#44; a glicemia elevada&#44; mas n&#227;o a presen&#231;a de SM <span class="elsevierStyleItalic">per se</span> ou dos outros componentes de SM permite predizer risco de morte ou enfarte no seguimento<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">22</span></a>&#46; Outros autores&#44; pelo contr&#225;rio&#44; mostraram que na presen&#231;a de doen&#231;a coron&#225;ria&#44; a SM tem impacto na mortalidade e na ocorr&#234;ncia de eventos coron&#225;rios a m&#233;dio e longo prazo<a class="elsevierStyleCrossRefs" href="#bib0265"><span class="elsevierStyleSup">23&#44;24</span></a>&#46; Contudo&#44; estes &#250;ltimos estudos foram realizados em popula&#231;&#245;es n&#227;o contempor&#226;neas &#40;d&#233;cada de 80 e 90&#41;&#44; com abordagens terap&#234;uticas diferentes das atuais e em popula&#231;&#245;es etnicamente diferentes &#40;na sua maioria japonesa&#41;&#44; bem como utilizando defini&#231;&#245;es mais antigas de SM&#46; Estudos mais recentes continuam a revelar controv&#233;rsia na influ&#234;ncia da SM na ocorr&#234;ncia de eventos<a class="elsevierStyleCrossRefs" href="#bib0195"><span class="elsevierStyleSup">9&#44;10</span></a>&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">Na presente an&#225;lise&#44; numa popula&#231;&#227;o mais contempor&#226;nea no tratamento da doen&#231;a coron&#225;ria&#44; demonstr&#225;mos que a presen&#231;a de SM em doentes com doen&#231;a coron&#225;ria n&#227;o tem impacto na ocorr&#234;ncia de mortalidade cardiovascular ou reinternamento por motivo cardiovascular&#46; Contudo&#44; &#233; aparente uma tend&#234;ncia importante para maior frequ&#234;ncia de eventos compostos&#44; s&#237;ndromes coron&#225;rias agudas no seguimento e menos internamentos por insufici&#234;ncia card&#237;aca&#46; A idade e a presen&#231;a de diabetes s&#227;o os fatores predizentes com maior impacto&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">O resultado relacionado com insufici&#234;ncia card&#237;aca foi algo surpreendente&#44; mas consultando literatura internacional&#44; encontramos outras evid&#234;ncias&#44; nomeadamente na resposta &#224; terap&#234;utica de ressincroniza&#231;&#227;o card&#237;aca que &#233; mais significativa nos indiv&#237;duos com SM<a class="elsevierStyleCrossRefs" href="#bib0275"><span class="elsevierStyleSup">25&#8208;28</span></a>&#46; Por um lado&#44; a propor&#231;&#227;o de mulheres nos grupos com SM &#233; superior e estudos anteriores descrevem que o impacto negativo na sobreviv&#234;ncia de doentes com insufici&#234;ncia card&#237;aca ocorre sobretudo no sexo masculino&#44; n&#227;o sendo observado nas mulheres<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">28</span></a>&#46; Por outro lado&#44; o efeito na sobreviv&#234;ncia no contexto de insufici&#234;ncia card&#237;aca &#233; sobretudo determinado pela presen&#231;a de diabetes e hipertens&#227;o&#44; dependendo por isso dos fatores de risco agregados em determinados indiv&#237;duos que &#233; muito heterog&#233;neo como j&#225; referido<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">28</span></a>&#46; Finalmente&#44; em indiv&#237;duos com insufici&#234;ncia card&#237;aca e obesidade e&#47;ou SM os mecanismos n&#227;o est&#227;o completamente esclarecidos<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">28</span></a>&#46; Alguns autores sugerem que o balan&#231;o entre a sobrecarga anab&#243;lica e catab&#243;lica est&#225; alterado nestes doentes&#44; conferindo um melhor progn&#243;stico<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">28</span></a>&#46; Na presen&#231;a de uma condi&#231;&#227;o que contrabalan&#231;a os efeitos de inflama&#231;&#227;o e m&#225; nutri&#231;&#227;o proteica&#44; como o excesso de peso ou a obesidade moderada&#44; poder&#225; ser ben&#233;fico em doentes com insufici&#234;ncia card&#237;aca&#46; Contudo&#44; esta associa&#231;&#227;o inversa entre obesidade ou SM descrita por outros autores e tamb&#233;m aparente no nosso estudo&#44; pode ser resultado de um vi&#233;s porque os doentes com obesidade e&#47;ou SM representam um subgrupo selecionado de doentes com insufici&#234;ncia card&#237;aca nos quais os fatores de risco confundentes associados a pior progn&#243;stico podem estar menos presentes&#46; Por outro lado&#44; por estes doentes referirem sintomas e sinais relacionados com obesidade&#44; podem condicionar uma avalia&#231;&#227;o card&#237;aca mais precoce com identifica&#231;&#227;o tamb&#233;m precoce dos casos de insufici&#234;ncia card&#237;aca e um tratamento mais agressivo atempado&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">Uma quest&#227;o relevante diz respeito &#224; defini&#231;&#227;o de SM que tem variado ao longo dos anos&#44; dificultando n&#227;o s&#243; a compara&#231;&#227;o de estudos&#44; mas com implica&#231;&#245;es importantes na preval&#234;ncia deste entidade<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">29</span></a>&#46; Contudo&#44; o risco de eventos cardiovasculares &#233; semelhante para todas as defini&#231;&#245;es&#44; independentemente da defini&#231;&#227;o<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">29</span></a>&#46; Em 2009&#44; as diversas sociedades cient&#237;ficas para o estudo da SM reuniram&#8208;se e publicaram a defini&#231;&#227;o harmonizada que foi a utilizada no presente estudo<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">16</span></a>&#46;</p><p id="par0185" class="elsevierStylePara elsevierViewall">Uma breve refer&#234;ncia tamb&#233;m ao facto de no nosso estudo apenas 41&#44;6&#37; dos indiv&#237;duos apresentarem doen&#231;a coron&#225;ria angiograficamente significativa&#46; Estes dados est&#227;o de acordo com dados internacionais&#44; tais como os dados publicados do <span class="elsevierStyleItalic">CathPCI Registry of the National Cardiovascular Data Registry</span>&#44; provenientes de uma amostra grande e representativa de doentes sem doen&#231;a card&#237;aca conhecida previamente submetidos a angiografia coron&#225;ria eletiva nos Estados Unidos da Am&#233;rica&#44; sendo esses dados ainda mais baixos do que os obtidos na nossa amostra<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">30</span></a>&#46; Nesse registo&#44; apenas 37&#44;6&#37; dos indiv&#237;duos submetidos a coronariografia apresentaram doen&#231;a coron&#225;ria obstrutiva&#44; definida por estenoses &#8805; 50&#37; do tronco comum ou &#8805; 70&#37; de um vaso epic&#225;rdico <span class="elsevierStyleItalic">major</span>&#46; Estes resultados demonstram as limita&#231;&#245;es da cl&#237;nica e mesmo dos testes de isquemia n&#227;o invasivos&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">Um coment&#225;rio final est&#225; relacionado com a aparente inexist&#234;ncia de associa&#231;&#227;o a neoplasias em doentes com SM num seguimento a longo&#8208;prazo&#44; ao contr&#225;rio do anteriormente reportado por outros estudos&#46;</p><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Limita&#231;&#245;es</span><p id="par0195" class="elsevierStylePara elsevierViewall">A principal limita&#231;&#227;o do estudo relaciona&#8208;se com o facto de a dimens&#227;o da amostra para o tempo de seguimento ser relativamente pequena e o n&#250;mero de eventos observados foi tamb&#233;m pequeno&#44; n&#227;o tendo poder estat&#237;stico para confirmar o impacto que tendencialmente &#233; aparente nos resultados apresentados&#46; Este facto n&#227;o permite tamb&#233;m realizar an&#225;lises mais detalhadas da influ&#234;ncia de cada componente da SM na ocorr&#234;ncia de eventos cardiovasculares&#46; Contudo&#44; os dados apresentados abrem uma janela de oportunidade para estudos mais alargados&#46;</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Conclus&#227;o</span><p id="par0200" class="elsevierStylePara elsevierViewall">Num seguimento a longo&#8208;prazo&#44; a presen&#231;a de doen&#231;a coron&#225;ria teve um impacto muito importante na ocorr&#234;ncia de eventos&#44; mas n&#227;o a presen&#231;a de SM&#44; questionando o impacto da obesidade e da SM em preven&#231;&#227;o secund&#225;ria&#46; Contudo&#44; ser&#225; necess&#225;ria uma an&#225;lise numa popula&#231;&#227;o de maiores dimens&#245;es e eventualmente com maior seguimento e maior n&#250;mero de eventos para se obterem conclus&#245;es mais definitivas&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Conflitos de interesse</span><p id="par0205" class="elsevierStylePara elsevierViewall">Os autores declaram n&#227;o haver conflitos de interesse&#46;</p></span></span>"
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            0 => "S&#237;ndrome metab&#243;lica"
            1 => "Doen&#231;a coron&#225;ria"
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            3 => "Progn&#243;stico"
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            0 => "Metabolic syndrome"
            1 => "Coronary artery disease"
            2 => "Cardiovascular events"
            3 => "Prognosis"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introdu&#231;&#227;o</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Doentes com obesidade t&#234;m um maior risco de eventos cardiovasculares em preven&#231;&#227;o prim&#225;ria&#46; Em preven&#231;&#227;o secund&#225;ria tem sido descrito um paradoxo da obesidade&#46; Foi nosso objetivo estudar uma coorte de indiv&#237;duos analisados previamente num estudo transversal sobre a rela&#231;&#227;o entre s&#237;ndrome metab&#243;lica &#40;SM&#41; e doen&#231;a coron&#225;ria &#40;DC&#41;&#44; estudando presentemente o impacto da SM na ocorr&#234;ncia de eventos cardiovasculares a longo&#8208;prazo&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">M&#233;todos</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Foram analisados 296 indiv&#237;duos num seguimento m&#233;dio de 6&#44;9 &#177; 2&#44;2 anos&#46; Os indiv&#237;duos foram divididos em quatro grupos em fun&#231;&#227;o da presen&#231;a ou aus&#234;ncia de SM e de DC &#40;estenoses coron&#225;rias &#8805; 70&#37;&#41;&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Resultados</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">A popula&#231;&#227;o analisada tinha uma idade de 65 &#177; 9 anos no in&#237;cio do estudo&#44; 59&#44;5&#37; do sexo masculino&#44; 55&#44;7&#37; com SM e 41&#44;6&#37; com DC&#46; No seguimento&#44; ocorreram 10&#44;1&#37; de mortes por todas as causas&#44; 3&#44;7&#37; mortes cardiovasculares&#44; 14&#44;2&#37; reinternamentos cardiovasculares e 22&#44;0&#37; de eventos compostos &#40;morte&#44; s&#237;ndrome coron&#225;ria aguda&#44; revasculariza&#231;&#227;o coron&#225;ria&#44; acidente vascular cerebral&#47;isqu&#233;mico transit&#243;rio&#44; admiss&#227;o por insufici&#234;ncia card&#237;aca&#41;&#46; N&#227;o se verificaram diferen&#231;as significativas em termos de mortalidade&#46; Ambos os grupos com DC tiveram mais reinternamentos e eventos compostos &#40;Log&#8208;<span class="elsevierStyleItalic">rank</span>&#44; p &#60; 0&#44;001 e p &#61; 0&#44;001&#44; respetivamente&#41;&#44; mas sem diferen&#231;as em rela&#231;&#227;o &#224; presen&#231;a de SM&#46; A DC foi preditora independente de reinternamento cardiovascular &#40;HR 3&#44;21&#44; IC 95&#37; 1&#44;66&#8211;6&#44;21&#41; e de eventos compostos &#40;HR 2&#44;41&#44; IC 95&#37; 1&#44;44&#8211;4&#44;02&#41;&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclus&#245;es</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Em doentes de elevado risco cardiovascular ou com doen&#231;a coron&#225;ria estabelecida&#44; a presen&#231;a de SM n&#227;o se associou a aumento de eventos cerebrais ou card&#237;acos num seguimento a longo&#8208;prazo&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
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            "titulo" => "Introdu&#231;&#227;o"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introduction</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Obese patients are at higher cardiovascular risk in primary prevention&#46; In secondary prevention&#44; an obesity paradox has been reported&#46; We analyzed a cohort of individuals from a previous cross&#8208;sectional study on the impact of metabolic syndrome &#40;MS&#41; on coronary artery disease &#40;CAD&#41;&#44; aiming to assess the occurrence of cardiovascular events in a long follow&#8208;up&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Methods</span><p id="spar0105" class="elsevierStyleSimplePara elsevierViewall">We analyzed 296 individuals in a mean follow&#8208;up of 6&#46;9&#177;2&#46;2 years&#46; Subjects were divided into four groups according to the presence of MS or CAD &#40;defined as &#8805;70&#37; coronary stenosis&#41;&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Results</span><p id="spar0110" class="elsevierStyleSimplePara elsevierViewall">The study population had a mean age of 65&#177;9 years at the beginning of the study&#59; 59&#46;5&#37; were male&#44; 55&#46;7&#37; had MS and 41&#46;6&#37; had CAD&#46; During follow&#8208;up 10&#46;1&#37; of the population suffered all&#8208;cause death&#44; 3&#46;7&#37; cardiovascular death&#44; 14&#46;2&#37; cardiovascular readmission and 22&#46;0&#37; the composite outcome &#40;mortality&#44; acute coronary syndrome&#44; coronary revascularization&#44; stroke&#47;transient ischemic attack or heart failure admission&#41;&#46; There were no significant differences in any type of mortality&#46; Patients with CAD had more readmissions and composite outcomes &#40;log&#8208;rank p&#60;0&#46;001 and p&#61;0&#46;001&#44; respectively&#41;&#44; but there was no difference according to the presence of MS&#46; Only CAD was an independent predictor of cardiovascular admission &#40;HR 3&#46;21&#44; 95&#37; CI 1&#46;66&#8208;6&#46;21&#41; and composite outcomes &#40;HR 2&#46;41&#44; 95&#37; CI 1&#46;44&#8208;4&#46;02&#41;&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusions</span><p id="spar0115" class="elsevierStyleSimplePara elsevierViewall">In patients with high cardiovascular risk or established CAD&#44; the presence of MS is not associated with cerebral or cardiac events in long&#8208;term follow&#8208;up&#46;</p></span>"
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Mortalidade de todas as causas</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>S&#237;ndrome metab&#243;lica&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;56&#8211;2&#44;52&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;652&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Doen&#231;a coron&#225;ria&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1&#44;17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#44;54&#8211;2&#44;42&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#44;672&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t  " colspan="4" align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Mortalidade cardiovascular</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>S&#237;ndrome metab&#243;lica&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#44;81&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#44;25&#8211;2&#44;67&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;730&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Doen&#231;a coron&#225;ria&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1&#44;45&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#44;44&#8211;4&#44;79&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#44;545&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t  " colspan="4" align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Admiss&#227;o cardiovascular</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>S&#237;ndrome metab&#243;lica&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#44;93&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;50&#8211;1&#44;73&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#44;818&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Doen&#231;a coron&#225;ria&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">3&#44;21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1&#44;66&#8211;6&#44;21&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#44;001&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1&#44;03&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#44;61&#8211;1&#44;74&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#44;901&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Doen&#231;a coron&#225;ria&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2&#44;41&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">1&#44;44&#8211;4&#44;02&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#44;001&nbsp;\t\t\t\t\t\t\n
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                  """
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        "descripcion" => array:1 [
          "pt" => "<p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">An&#225;lise multivariada de Cox sobre efeito preditor da s&#237;ndrome metab&#243;lica e&#47;ou doen&#231;a coron&#225;ria na ocorr&#234;ncia de eventos</p>"
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      "titulo" => "Refer&#234;ncias"
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        0 => array:2 [
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            0 => array:3 [
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Cardiovascular diseases in Europe&#58; epidemiological update 2016"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "N&#46; Townsend"
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                            2 => "P&#46; Bhatnagar"
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                    0 => array:2 [
                      "doi" => "10.1093/eurheartj/ehw334"
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur Heart J&#46;"
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                        "volumen" => "37"
                        "paginaInicial" => "3232"
                        "paginaFinal" => "3245"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27523477"
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              "identificador" => "bib0160"
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                0 => array:1 [
                  "referenciaCompleta" => "Programa Nacional para as doen&#231;as c&#233;rebro&#8208;cardiovasculares 2017&#46; Ed&#46; Dire&#231;&#227;o Geral Sa&#250;de&#44; Lisboa&#44; Setembro 2017&#44; p&#225;gina 5&#46;"
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            2 => array:3 [
              "identificador" => "bib0165"
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                0 => array:1 [
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                      "titulo" => "Metabolic syndrome and risk of cardiovascular disease&#58; a meta&#8208;analysis"
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                          "etal" => false
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                            0 => "A&#46; Galassi"
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                      "doi" => "10.1016/j.amjmed.2006.02.031"
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                        "volumen" => "119"
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                      "titulo" => "Metabolic syndrome and risk of incident cardiovascular events and death&#58; a systematic review and meta&#8208;analysis of longitudinal studies"
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                          "etal" => true
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                            0 => "A&#46;S&#46; Gami"
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                        "paginaInicial" => "403"
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                      "titulo" => "The metabolic syndrome and cardiovascular risk&#58; a systematic review and meta&#8208;analysis"
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                          "etal" => true
                          "autores" => array:3 [
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                            1 => "K&#46;B&#46; Filion"
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                      "doi" => "10.1016/j.jacc.2010.05.034"
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                        "tituloSerie" => "J Am Coll Cardiol&#46;"
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                        "volumen" => "56"
                        "paginaInicial" => "1113"
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                      "titulo" => "Metabolic syndrome &#40;MetS&#41; predicts cardio and cerebrovascular events in a twenty years follow&#8208;up&#46; A prospective study"
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                          "etal" => true
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                            1 => "A&#46; Peritore"
                            2 => "F&#46;P&#46; Guameri"
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                    ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.atherosclerosis.2012.05.018"
                      "Revista" => array:6 [
                        "tituloSerie" => "Atherosclerosis&#46;"
                        "fecha" => "2012"
                        "volumen" => "223"
                        "paginaInicial" => "468"
                        "paginaFinal" => "472"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22704563"
                            "web" => "Medline"
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                  "contribucion" => array:1 [
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                      "titulo" => "&#40;em nome dos investigadores do estudo VALSIM&#41; S&#237;ndrome Metab&#243;lica em Portugal&#58; Preval&#234;ncia e Implica&#231;&#245;es no Risco Cardiovascular &#8211; Resultados do Estudo VALSIM"
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                          "etal" => true
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                            1 => "N&#46; Cortez-Dias"
                            2 => "S&#46; Martins"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Rev Port Cardiol&#46;"
                        "fecha" => "2008"
                        "volumen" => "27"
                        "paginaInicial" => "1495"
                        "paginaFinal" => "1529"
                        "link" => array:1 [
                          0 => array:2 [
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                            "web" => "Medline"
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                0 => array:2 [
                  "contribucion" => array:1 [
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                      "titulo" => "Metabolic syndrome cluster does not provide incremental prognostic information in patients with stable cardiovascular disease&#58; A post hoc analysis of the AIM&#8208;HIGH trial"
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                          "etal" => true
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                    0 => array:2 [
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                      "Revista" => array:6 [
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Artigo Original
Será a síndrome metabólica um marcador de prognóstico em doentes com elevado risco cardiovascular? Um estudo de coorte a longo‐prazo
Is metabolic syndrome a prognostic marker in patients at high cardiovascular risk? A long‐term cohort study
Ana Teresa Timóteoa,b,
Autor para correspondência
ana_timoteo@yahoo.com

Autor para correspondência.
, Miguel Mota Carmob, Cristina Soaresa, Rui Cruz Ferreiraa
a Serviço de Cardiologia, Hospital de Santa Marta, Centro Hospitalar Universitário Lisboa Central, Lisboa, Portugal
b Centro de Estudos de Doenças Crónicas (CEDOC), NOVA Medical School, Lisboa, Portugal
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introdu&#231;&#227;o</span><p id="par0065" class="elsevierStylePara elsevierViewall">As doen&#231;as cardiovasculares s&#227;o ainda a principal causa de morte na Europa e Portugal n&#227;o &#233; exce&#231;&#227;o&#44; apesar do decr&#233;scimo progressivo que se tem verificado nas &#250;ltimas d&#233;cadas<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">1&#8211;3</span></a>&#46; Este facto observa&#8208;se na popula&#231;&#227;o geral&#44; mas em 2015 os tumores malignos j&#225; ultrapassam as doen&#231;as do aparelho circulat&#243;rio como principal causa de morte no sexo masculino<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">3</span></a>&#46; Para al&#233;m dos fatores de risco cardiovasculares j&#225; bem estabelecidos&#44; como a hipertens&#227;o arterial &#40;HTA&#41;&#44; o tabagismo&#44; a diabetes&#44; a eleva&#231;&#227;o do colesterol&#8208;LDL&#44; a idade e a hist&#243;ria familiar&#44; diversos outros fatores de risco t&#234;m vindo a ser valorizados nos &#250;ltimos anos&#46; Em particular&#44; a s&#237;ndrome metab&#243;lica &#40;SM&#41;&#44; uma agrega&#231;&#227;o de diversos fatores de risco&#44; pela sua elevada preval&#234;ncia a n&#237;vel mundial&#44; atingindo um padr&#227;o quase epid&#233;mico e pela associa&#231;&#227;o j&#225; demonstrada ao desenvolvimento de diabetes tipo 2 e doen&#231;as cardiovasculares &#40;num risco que pode ser at&#233; duas vezes superior&#41;&#44; tem sido um problema importante&#44; agravado pelo facto de o seu tratamento depender de uma profunda altera&#231;&#227;o dos estilos de vida&#44; muitas vezes dif&#237;ceis de implementar na popula&#231;&#227;o geral<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">4&#8211;6</span></a>&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Diversas meta&#8208;an&#225;lises pr&#233;vias demonstraram claramente que em preven&#231;&#227;o prim&#225;ria existe uma associa&#231;&#227;o clara entre a presen&#231;a de SM e a ocorr&#234;ncia de eventos cardiovasculares no seguimento<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">4&#8211;7</span></a>&#46; O mesmo foi demonstrado no estudo VALSIM realizado numa popula&#231;&#227;o portuguesa<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">8</span></a>&#46; Em preven&#231;&#227;o secund&#225;ria&#44; os resultados s&#227;o contradit&#243;rios&#44; com alguns estudos mostrando efeito neutro e outros maior incid&#234;ncia de eventos cardiovasculares&#44; mas com seguimentos inferiores a tr&#234;s anos<a class="elsevierStyleCrossRefs" href="#bib0195"><span class="elsevierStyleSup">9&#44;10</span></a>&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Em trabalhos pr&#233;vios&#44; demonstr&#225;mos que a presen&#231;a de SM <span class="elsevierStyleItalic">per se</span> n&#227;o se associa &#224; presen&#231;a de aterosclerose subcl&#237;nica &#40;avaliada pela espessura &#237;ntima&#8208;m&#233;dia da car&#243;tida comum &#8211; EIMc&#41; mas que alguns dos componentes desta s&#237;ndrome&#44; nomeadamente a hiperinsulin&#233;mia&#44; hiperglicemia e os n&#237;veis baixos do colesterol&#8208;HDL&#44; est&#227;o diretamente associados&#44; demostrando o efeito heterog&#233;neo dos diversos componentes da entidade SM<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">11&#8211;13</span></a>&#46; Do mesmo modo&#44; tamb&#233;m n&#227;o se constatou rela&#231;&#227;o direta com a presen&#231;a de doen&#231;a coron&#225;ria angiograficamente significativa &#40;avaliada em contexto est&#225;vel&#41;&#44; sendo a hiperglicemia e a hipertriglicerid&#233;mia os componentes preditores de presen&#231;a de doen&#231;a coron&#225;ria<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">14</span></a>&#46; Em ambos os estudos&#44; o per&#237;metro abdominal mostrou um efeito paradoxal&#44; protetor<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">12&#44;14</span></a>&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Estes trabalhos iniciais tiveram origem num estudo transversal e observacional&#46; Passados mais de cinco anos desde esta an&#225;lise&#44; temos como presente objetivo analisar o mesmo grupo de doentes e verificar num seguimento a longo&#8208;prazo &#40;superior a cinco anos&#41; se a presen&#231;a de SM se associa a maior ocorr&#234;ncia de mortalidade ou maior incid&#234;ncia de eventos cerebrais ou cardiovasculares&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">M&#233;todos</span><p id="par0085" class="elsevierStylePara elsevierViewall">Inclu&#237;ram&#8208;se no trabalho original indiv&#237;duos adultos &#40;&#8805; 18 anos&#41; admitidos eletivamente para realiza&#231;&#227;o de coronariografia por suspeita de doen&#231;a coron&#225;ria &#40;por queixas de angor e&#47;ou isquemia documentada por testes n&#227;o invasivos&#41; entre 2008 e 2010&#46; Foram exclu&#237;dos doentes com antecedentes de s&#237;ndrome coron&#225;ria aguda&#44; revasculariza&#231;&#227;o mioc&#225;rdica pr&#233;via ou doen&#231;a coron&#225;ria conhecida&#44; doen&#231;a valvular significativa&#44; cardiopatia cong&#233;nita ou outras miocardiopatias&#46; Nos trabalhos originais&#44; foi utilizada a defini&#231;&#227;o de SM da <span class="elsevierStyleItalic">American Heart Association&#47;National Heart Lung and Blood Institute</span><a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">15</span></a>&#46; Contudo&#44; presentemente&#44; a defini&#231;&#227;o foi harmonizada pelas diversas sociedades cient&#237;ficas&#44; sendo a principal diferen&#231;a a possibilidade de cada pa&#237;s&#47;regi&#227;o poder definir os limites de obesidade abdominal tendo em conta padr&#245;es &#233;tnicos<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">16</span></a>&#46; Utiliz&#225;mos ent&#227;o a nova defini&#231;&#227;o e consider&#225;mos os limites anteriormente definidos para o per&#237;metro abdominal &#40;&#8805; 88<span class="elsevierStyleHsp" style=""></span>cm para as mulheres e &#8805; 102<span class="elsevierStyleHsp" style=""></span>cm para os homens&#41;&#46; Os outros crit&#233;rios s&#227;o uma press&#227;o arterial &#8805; 130&#47;85<span class="elsevierStyleHsp" style=""></span>mmHg &#40;ou sob terap&#234;utica especifica&#41;&#44; colesterol&#8208;HDL &#8804; 40<span class="elsevierStyleHsp" style=""></span>mg&#47;dL nos homens ou &#8804; 50<span class="elsevierStyleHsp" style=""></span>mg&#47;dL nas mulheres &#40;ou sob terap&#234;utica especifica&#41;&#44; triglic&#233;ridos &#8805; 150<span class="elsevierStyleHsp" style=""></span>mg&#47;dL &#40;ou sob terap&#234;utica especifica&#41; e glicemia &#8805; 100<span class="elsevierStyleHsp" style=""></span>mg&#47;dL &#40;ou sob terap&#234;utica espec&#237;fica&#41;<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">15&#44;16</span></a>&#46; A SM &#233; definida pela presen&#231;a de pelo menos tr&#234;s dos crit&#233;rios referidos&#46; A presen&#231;a de doen&#231;a coron&#225;ria angiograficamente significativa foi definida pela presen&#231;a de estenose &#8805; 70&#37; em qualquer vaso coron&#225;rio epic&#225;rdico&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">Em todos os doentes&#44; a informa&#231;&#227;o de seguimento foi obtida por entrevista telef&#243;nica com o doente ou com familiares diretos aos 30 dias e ao primeiro ano ap&#243;s o internamento por uma equipa especialmente dedicada &#224; colheita de dados de seguimento dos doentes internados no servi&#231;o&#46; Em 2017&#44; realizou&#8208;se novo contacto para obter informa&#231;&#227;o adicional de seguimento desta coorte espec&#237;fica&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Foram considerados e analisados v&#225;rios eventos no seguimento&#46; A mortalidade de todas as causas define&#8208;se como morte por qualquer motivo&#46; A mortalidade de causa cardiovascular define&#8208;se como morte associada a patologia cardiovascular&#46; S&#237;ndrome coron&#225;ria aguda foi definida pela presen&#231;a de angor em repouso &#40;ou equivalente de angor&#41; com altera&#231;&#245;es no ECG e&#47;ou subida&#47;descida de marcadores de necrose mioc&#225;rdica&#46; Quando foi realizada angioplastia coron&#225;ria ou cirurgia de revasculariza&#231;&#227;o mioc&#225;rdica durante o seguimento&#44; sem rela&#231;&#227;o com o motivo de internamento inicial&#44; considerou&#8208;se a ocorr&#234;ncia de revasculariza&#231;&#227;o mioc&#225;rdica&#46; Internamento por insufici&#234;ncia card&#237;aca definiu&#8208;se como internamento por aparecimento&#47;agravamento de sintomas ou sinais de insufici&#234;ncia card&#237;aca&#46; Readmiss&#227;o cardiovascular foi considerada sempre que o doente foi internado por motivo cardiovascular agudo ou eletivo&#46; Acidente vascular cerebral &#40;AVC&#41;&#47;acidente isqu&#233;mico transit&#243;rio &#40;AIT&#41; foi definido pela presen&#231;a de instala&#231;&#227;o de novo de d&#233;ficits neurol&#243;gicos&#46; Foi tamb&#233;m analisado um composto de v&#225;rios eventos card&#237;acos e cerebrais &#40;mortalidade de todas as causas&#44; s&#237;ndrome coron&#225;ria aguda&#44; revasculariza&#231;&#227;o mioc&#225;rdica&#44; AVC&#47;AIT ou admiss&#227;o por insufici&#234;ncia card&#237;aca&#41;&#46; Nos doentes com eventos&#44; foi realizada an&#225;lise do processo cl&#237;nico para confirma&#231;&#227;o e classifica&#231;&#227;o adequada do evento ou foi solicitado ao doente informa&#231;&#227;o adicional&#46; Efetuou&#8208;se compara&#231;&#227;o destes eventos em doentes com e sem doen&#231;a coron&#225;ria&#44; bem como em doentes com e sem SM&#44; dividindo assim os indiv&#237;duos por quatro grupos&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">Todos os indiv&#237;duos assinaram consentimento informado para a participa&#231;&#227;o no estudo e o presente trabalho est&#225; de acordo com a Declara&#231;&#227;o de Helsinquia&#46;</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">An&#225;lise estat&#237;stica</span><p id="par0105" class="elsevierStylePara elsevierViewall">As vari&#225;veis cont&#237;nuas est&#227;o reportadas como m&#233;dia e desvio&#8208;padr&#227;o&#46; Foi testada a normalidade com recurso ao teste de Kolmogorov&#8208;Smirnov&#46; A compara&#231;&#227;o das vari&#225;veis cont&#237;nuas foi efetuada pelo teste ANOVA&#46; As vari&#225;veis categ&#243;ricas est&#227;o descritas como percentagens e foram comparadas com o teste qui&#8208;quadrado ou o teste de Fischer&#44; conforme apropriado&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">As estimativas de sobreviv&#234;ncia livre de eventos no seguimento foram calculadas pelo m&#233;todo de Kaplan&#8208;Meier e as curvas foram comparadas pelo teste <span class="elsevierStyleItalic">Log&#8208;rank</span>&#46; Foi utilizada a an&#225;lise de Cox <span class="elsevierStyleItalic">proportional&#8208;hazards</span> para analisar a influ&#234;ncia da presen&#231;a de SM e de doen&#231;a coron&#225;ria angiograficamente significativa na ocorr&#234;ncia de eventos a longo prazo e ajustada para as vari&#225;veis com impacto significativo no progn&#243;stico&#46; As estimativas de associa&#231;&#227;o entre os preditores e os eventos est&#227;o apresentadas como <span class="elsevierStyleItalic">Hazard Ratios</span> &#40;HR&#41; e intervalo de confian&#231;a de 95&#37;&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">Foi utilizado o programa IBM SPSS <span class="elsevierStyleItalic">statistical software package</span> &#40;vers&#227;o 19&#46;0&#46;0&#46;2&#41; e considerado um valor de p inferior a 0&#44;05 como estatisticamente significativo&#46;</p></span></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Resultados</span><p id="par0120" class="elsevierStylePara elsevierViewall">Foram inclu&#237;dos no estudo inicial 300 doentes&#44; tendo quatro doentes sido perdidos no seguimento&#46; Dos 296 doentes inclu&#237;dos na presente an&#225;lise&#44; 59&#37; s&#227;o do sexo masculino&#44; com idade m&#233;dia de 65 &#177; 9 anos &#40;38&#8208;86 anos&#41;&#46; A preval&#234;ncia de SM &#233; de 55&#44;7&#37; e o componente mais prevalente de SM foi a HTA&#44; seguido pela obesidade abdominal&#44; glicemia elevada&#44; colesterol&#8208;HDL baixo e triglic&#233;ridos elevados &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">tabela 1</a>&#41;&#46; Em apenas 41&#44;6&#37; dos indiv&#237;duos se detetou a presen&#231;a de doen&#231;a coron&#225;ria angiograficamente significativa&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0125" class="elsevierStylePara elsevierViewall">Num seguimento m&#233;dio de 6&#44;9 &#177; 2&#44;2 anos&#44; ocorreram 10&#44;1&#37; de mortes de todas as causas&#44; 3&#44;7&#37; de mortes cardiovasculares&#44; 14&#44;2&#37; de admiss&#245;es de causa cardiovascular e 22&#44;0&#37; de eventos compostos &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">tabela 2</a>&#41;&#46; N&#227;o se verificaram diferen&#231;as estatisticamente significativas em termos de mortalidade de todas as causas ou cardiovasculares comparando todos os grupos &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">tabela 2</a> e <a class="elsevierStyleCrossRefs" href="#fig0005">figuras 1 e 2</a>&#41;&#46; Pelo contr&#225;rio&#44; os reinternamentos de causa cardiovascular e os eventos compostos foram mais frequentes nos grupos com doen&#231;a coron&#225;ria &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">tabela 2</a> e <a class="elsevierStyleCrossRefs" href="#fig0015">figuras 3 e 4</a>&#41;&#46; Esta diferen&#231;a foi particularmente condicionada por maior ocorr&#234;ncia de s&#237;ndrome coron&#225;ria aguda no grupo com SM e DC &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">tabela 2</a>&#41;&#46; Ambos os grupos de DC mostram maior realiza&#231;&#227;o de ICP e readmiss&#227;o cardiovascular &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">tabela 2</a>&#41;&#46; A DC associou&#8208;se a mais eventos&#46; Com efeito&#44; nos indiv&#237;duos sem SM&#44; as readmiss&#245;es cardiovasculares e os eventos compostos foram significativamente mais frequentes na presen&#231;a de doen&#231;a coron&#225;ria &#40;<span class="elsevierStyleItalic">Log&#8208;rank</span>&#44; p &#61; 0&#44;001 e p &#61; 0&#44;004&#44; respetivamente&#41;&#44; verificando&#8208;se o mesmo nos indiv&#237;duos com SM &#40;<span class="elsevierStyleItalic">Log&#8208;rank</span>&#44; p &#61; 0&#44;007 e p &#61; 0&#44;002&#44; respetivamente&#41;&#46; Na presen&#231;a de doen&#231;a coron&#225;ria&#44; verificou&#8208;se que a presen&#231;a concomitante de SM se associou a uma tend&#234;ncia para maior morte de todas as causas &#40;<span class="elsevierStyleItalic">Log&#8208;rank</span>&#44; p &#61; 0&#44;382&#41; e para os eventos compostos &#40;<span class="elsevierStyleItalic">Log&#8208;rank</span>&#44; p &#61; 0&#44;365&#41; &#40;<a class="elsevierStyleCrossRefs" href="#fig0005">figuras 1 e 4</a>&#41;&#46; Tamb&#233;m se verifica maior ocorr&#234;ncia de s&#237;ndrome coron&#225;ria aguda&#44; embora sem atingir significado estat&#237;stico &#40;<span class="elsevierStyleItalic">Log&#8208;rank</span>&#44; p &#61; 0&#44;094&#41; mas com uma clara tend&#234;ncia para mais eventos&#46; Os grupos com SM tiveram menos internamentos por insufici&#234;ncia card&#237;aca&#46; A incid&#234;ncia de neoplasias foi semelhante na presen&#231;a ou aus&#234;ncia de SM&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia><p id="par0130" class="elsevierStylePara elsevierViewall">Em an&#225;lise multivariada&#44; apenas a presen&#231;a de doen&#231;a coron&#225;ria foi preditora independente de internamento cardiovascular e eventos compostos&#44; mas n&#227;o de mortalidade &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">tabela 3</a>&#41;&#46; A SM n&#227;o foi preditora independente de nenhum dos eventos considerados&#46; A idade foi preditora independente de morte de todas as causas &#40;HR 1&#44;1&#44; p &#60; 0&#44;001&#41;&#44; morte cardiovascular &#40;HR 1&#44;13&#44; p &#61; 0&#44;002&#41;&#44; reinternamento cardiovascular &#40;HR 1&#44;05&#44; p &#61; 0&#44;020&#41; e eventos compostos &#40;HR 1&#44;07&#44; p &#60; 0&#44;001&#41;&#46; A diabetes foi preditora independente de morte de todas as causas &#40;HR 3&#44;11&#44; p &#61; 0&#44;004&#41; e eventos compostos &#40;HR 1&#44;97&#44; p &#61; 0&#44;012&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Discuss&#227;o</span><p id="par0135" class="elsevierStylePara elsevierViewall">Em meta&#8208;an&#225;lises pr&#233;vias &#40;em doentes na sua maioria em preven&#231;&#227;o prim&#225;ria&#41; foi demonstrada a associa&#231;&#227;o entre SM e eventos cardiovasculares<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">4&#8211;7</span></a>&#46; Esta associa&#231;&#227;o manteve&#8208;se mesmo ap&#243;s ajuste para outros fatores de risco&#44; o que corrobora a exist&#234;ncia de um fen&#243;meno de potencia&#231;&#227;o de risco e relev&#226;ncia epidemiol&#243;gica&#46; Com efeito&#44; a presen&#231;a de SM associou&#8208;se a um aumento de duas vezes do risco de doen&#231;a cardiovascular&#44; mortalidade cardiovascular&#44; enfarte do mioc&#225;rdio e acidente vascular cerebral e aumento de 1&#44;5 vezes no risco de mortalidade total<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">6</span></a>&#46; Assim&#44; os doentes com SM apresentam maior risco para eventos cardiovasculares do que para mortalidade total&#46; Mesmo na aus&#234;ncia de diabetes <span class="elsevierStyleItalic">mellitus</span>&#44; a presen&#231;a de SM associou&#8208;se a aumento de risco de mortalidade cardiovascular&#44; enfarte mioc&#225;rdio e AVC&#44; n&#227;o sendo&#44; contudo&#44; significativo para a mortalidade total<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">6</span></a>&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">Em Portugal&#44; no estudo VALSIM&#44; a SM associou&#8208;se de forma independente &#224; presen&#231;a de doen&#231;a coron&#225;ria &#40;definida como angina e&#47;ou hist&#243;ria pr&#233;via de enfarte do mioc&#225;rdio&#41; e particularmente &#224; presen&#231;a de diabetes&#44; confirmando a sua relev&#226;ncia cl&#237;nica na ocorr&#234;ncia de doen&#231;a cardiovascular em Portugal<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">8</span></a>&#46; A hipertens&#227;o &#233; o componente de SM que se associou de forma mais potente com a ocorr&#234;ncia de doen&#231;a cardiovascular&#44; tendo&#8208;se&#44; contudo&#44; destacado tamb&#233;m com alguma relev&#226;ncia a eleva&#231;&#227;o da glicemia&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">Os estudos em preven&#231;&#227;o secund&#225;ria t&#234;m mostrado resultados contradit&#243;rios&#44; com alguns a mostrar impacto na ocorr&#234;ncia de eventos e outros com efeito neutro&#44; mas na sua maioria n&#227;o ultrapassando os 36 meses de seguimento<a class="elsevierStyleCrossRefs" href="#bib0195"><span class="elsevierStyleSup">9&#44;10</span></a>&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">Um estudo com ecografia intracoron&#225;ria mostrou que nos indiv&#237;duos com SM existe uma alta preval&#234;ncia de placas com elevado conte&#250;do lip&#237;dico&#44; mais inst&#225;veis&#44; sendo a SM fator preditor independente deste tipo de placas<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">17&#44;18</span></a>&#46; Contudo&#44; em preven&#231;&#227;o secund&#225;ria&#44; o refor&#231;o da terap&#234;utica farmacol&#243;gica&#44; nomeadamente as estatinas&#44; t&#234;m impacto conhecido na redu&#231;&#227;o de eventos por estabiliza&#231;&#227;o das placas ateroscler&#243;ticas&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">Por outro lado&#44; a SM &#233; uma entidade muito heterog&#233;nea&#44; dependendo do tipo de agrega&#231;&#227;o de fatores de risco&#46; No estudo MESYAS realizado em Espanha&#44; o risco de doen&#231;a cardiovascular &#233; vari&#225;vel consoante o componente analisado&#44; com alguns componentes isolados de SM a conferirem diferentes intensidades de risco<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">19</span></a>&#46; Com efeito&#44; o risco associado a SM &#233; plenamente explicado pelos seus componentes considerados individualmente&#46; A hipertriglicerid&#233;mia foi o componente que conferiu maior risco&#46; Pelo contr&#225;rio&#44; a obesidade &#40;avaliada pelo IMC&#41; n&#227;o foi um fator independente de risco para doen&#231;a cardiovascular&#44; parecendo mesmo ser protetor&#46; A sobrecarga cardiovascular associada &#224; obesidade parece assim ser condicionada principalmente pelo aparecimento de outros fatores de risco metab&#243;licos como a hiperglicemia&#44; dislipid&#233;mia aterog&#233;nica e a hipertens&#227;o&#46; Tendo em conta que a SM resulta de uma agrega&#231;&#227;o de pelo menos tr&#234;s fatores de risco&#44; temos como consequ&#234;ncia a exist&#234;ncia de uma grande heterogeneidade de risco entre os doentes com SM dependente dos crit&#233;rios utilizados para o diagn&#243;stico&#46; Na presen&#231;a de obesidade&#44; &#233; necess&#225;ria a presen&#231;a de apenas outros dois fatores de risco&#46; Contudo&#44; na aus&#234;ncia de obesidade&#44; s&#227;o necess&#225;rios outros tr&#234;s componentes que apresentam um risco cardiovascular muito mais significativo&#46; Assim&#44; o tipo de componentes agregados poder&#225; ser importante para o desenvolvimento de doen&#231;a coron&#225;ria&#44; em particular se estiverem envolvidos em simult&#226;neo a eleva&#231;&#227;o da glicemia e dislipid&#233;mia aterog&#233;nica&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">Com efeito&#44; estudos longitudinais encontraram uma incid&#234;ncia de eventos cardiovasculares id&#234;ntica entre obesos metabolicamente benignos &#40;definidos pela aus&#234;ncia de s&#237;ndrome metab&#243;lico e diabetes&#41; e indiv&#237;duos com peso normal&#44; em contraste com o elevado risco cardiovascular em indiv&#237;duos obesos de alto risco&#44; com agrega&#231;&#227;o de fatores de risco cardiometab&#243;licos<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">20</span></a>&#46; Uma an&#225;lise dos dados de tr&#234;s grandes estudos &#40;<span class="elsevierStyleItalic">Framingham Offspring Study&#44; Atherosclerosis Risk In Communities</span> e <span class="elsevierStyleItalic">Cardiovascular Health Study</span>&#41; mostrou que a presen&#231;a de componentes de SM&#44; de SM propriamente dito ou de diabetes associa&#8208;se a um aumento de duas a cinco vezes do risco de eventos coron&#225;rios ou AVC num seguimento m&#233;dio de oito anos&#44; mesmo tendo em conta a obesidade abdominal<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">21</span></a>&#44; sugerindo que a presen&#231;a de anomalias metab&#243;licas &#233; um fator preditor substancialmente mais forte do que a obesidade abdominal na incid&#234;ncia de eventos cardiovasculares&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">Quando existe doen&#231;a coron&#225;ria estabelecida&#44; a glicemia elevada&#44; mas n&#227;o a presen&#231;a de SM <span class="elsevierStyleItalic">per se</span> ou dos outros componentes de SM permite predizer risco de morte ou enfarte no seguimento<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">22</span></a>&#46; Outros autores&#44; pelo contr&#225;rio&#44; mostraram que na presen&#231;a de doen&#231;a coron&#225;ria&#44; a SM tem impacto na mortalidade e na ocorr&#234;ncia de eventos coron&#225;rios a m&#233;dio e longo prazo<a class="elsevierStyleCrossRefs" href="#bib0265"><span class="elsevierStyleSup">23&#44;24</span></a>&#46; Contudo&#44; estes &#250;ltimos estudos foram realizados em popula&#231;&#245;es n&#227;o contempor&#226;neas &#40;d&#233;cada de 80 e 90&#41;&#44; com abordagens terap&#234;uticas diferentes das atuais e em popula&#231;&#245;es etnicamente diferentes &#40;na sua maioria japonesa&#41;&#44; bem como utilizando defini&#231;&#245;es mais antigas de SM&#46; Estudos mais recentes continuam a revelar controv&#233;rsia na influ&#234;ncia da SM na ocorr&#234;ncia de eventos<a class="elsevierStyleCrossRefs" href="#bib0195"><span class="elsevierStyleSup">9&#44;10</span></a>&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">Na presente an&#225;lise&#44; numa popula&#231;&#227;o mais contempor&#226;nea no tratamento da doen&#231;a coron&#225;ria&#44; demonstr&#225;mos que a presen&#231;a de SM em doentes com doen&#231;a coron&#225;ria n&#227;o tem impacto na ocorr&#234;ncia de mortalidade cardiovascular ou reinternamento por motivo cardiovascular&#46; Contudo&#44; &#233; aparente uma tend&#234;ncia importante para maior frequ&#234;ncia de eventos compostos&#44; s&#237;ndromes coron&#225;rias agudas no seguimento e menos internamentos por insufici&#234;ncia card&#237;aca&#46; A idade e a presen&#231;a de diabetes s&#227;o os fatores predizentes com maior impacto&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">O resultado relacionado com insufici&#234;ncia card&#237;aca foi algo surpreendente&#44; mas consultando literatura internacional&#44; encontramos outras evid&#234;ncias&#44; nomeadamente na resposta &#224; terap&#234;utica de ressincroniza&#231;&#227;o card&#237;aca que &#233; mais significativa nos indiv&#237;duos com SM<a class="elsevierStyleCrossRefs" href="#bib0275"><span class="elsevierStyleSup">25&#8208;28</span></a>&#46; Por um lado&#44; a propor&#231;&#227;o de mulheres nos grupos com SM &#233; superior e estudos anteriores descrevem que o impacto negativo na sobreviv&#234;ncia de doentes com insufici&#234;ncia card&#237;aca ocorre sobretudo no sexo masculino&#44; n&#227;o sendo observado nas mulheres<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">28</span></a>&#46; Por outro lado&#44; o efeito na sobreviv&#234;ncia no contexto de insufici&#234;ncia card&#237;aca &#233; sobretudo determinado pela presen&#231;a de diabetes e hipertens&#227;o&#44; dependendo por isso dos fatores de risco agregados em determinados indiv&#237;duos que &#233; muito heterog&#233;neo como j&#225; referido<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">28</span></a>&#46; Finalmente&#44; em indiv&#237;duos com insufici&#234;ncia card&#237;aca e obesidade e&#47;ou SM os mecanismos n&#227;o est&#227;o completamente esclarecidos<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">28</span></a>&#46; Alguns autores sugerem que o balan&#231;o entre a sobrecarga anab&#243;lica e catab&#243;lica est&#225; alterado nestes doentes&#44; conferindo um melhor progn&#243;stico<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">28</span></a>&#46; Na presen&#231;a de uma condi&#231;&#227;o que contrabalan&#231;a os efeitos de inflama&#231;&#227;o e m&#225; nutri&#231;&#227;o proteica&#44; como o excesso de peso ou a obesidade moderada&#44; poder&#225; ser ben&#233;fico em doentes com insufici&#234;ncia card&#237;aca&#46; Contudo&#44; esta associa&#231;&#227;o inversa entre obesidade ou SM descrita por outros autores e tamb&#233;m aparente no nosso estudo&#44; pode ser resultado de um vi&#233;s porque os doentes com obesidade e&#47;ou SM representam um subgrupo selecionado de doentes com insufici&#234;ncia card&#237;aca nos quais os fatores de risco confundentes associados a pior progn&#243;stico podem estar menos presentes&#46; Por outro lado&#44; por estes doentes referirem sintomas e sinais relacionados com obesidade&#44; podem condicionar uma avalia&#231;&#227;o card&#237;aca mais precoce com identifica&#231;&#227;o tamb&#233;m precoce dos casos de insufici&#234;ncia card&#237;aca e um tratamento mais agressivo atempado&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">Uma quest&#227;o relevante diz respeito &#224; defini&#231;&#227;o de SM que tem variado ao longo dos anos&#44; dificultando n&#227;o s&#243; a compara&#231;&#227;o de estudos&#44; mas com implica&#231;&#245;es importantes na preval&#234;ncia deste entidade<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">29</span></a>&#46; Contudo&#44; o risco de eventos cardiovasculares &#233; semelhante para todas as defini&#231;&#245;es&#44; independentemente da defini&#231;&#227;o<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">29</span></a>&#46; Em 2009&#44; as diversas sociedades cient&#237;ficas para o estudo da SM reuniram&#8208;se e publicaram a defini&#231;&#227;o harmonizada que foi a utilizada no presente estudo<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">16</span></a>&#46;</p><p id="par0185" class="elsevierStylePara elsevierViewall">Uma breve refer&#234;ncia tamb&#233;m ao facto de no nosso estudo apenas 41&#44;6&#37; dos indiv&#237;duos apresentarem doen&#231;a coron&#225;ria angiograficamente significativa&#46; Estes dados est&#227;o de acordo com dados internacionais&#44; tais como os dados publicados do <span class="elsevierStyleItalic">CathPCI Registry of the National Cardiovascular Data Registry</span>&#44; provenientes de uma amostra grande e representativa de doentes sem doen&#231;a card&#237;aca conhecida previamente submetidos a angiografia coron&#225;ria eletiva nos Estados Unidos da Am&#233;rica&#44; sendo esses dados ainda mais baixos do que os obtidos na nossa amostra<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">30</span></a>&#46; Nesse registo&#44; apenas 37&#44;6&#37; dos indiv&#237;duos submetidos a coronariografia apresentaram doen&#231;a coron&#225;ria obstrutiva&#44; definida por estenoses &#8805; 50&#37; do tronco comum ou &#8805; 70&#37; de um vaso epic&#225;rdico <span class="elsevierStyleItalic">major</span>&#46; Estes resultados demonstram as limita&#231;&#245;es da cl&#237;nica e mesmo dos testes de isquemia n&#227;o invasivos&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">Um coment&#225;rio final est&#225; relacionado com a aparente inexist&#234;ncia de associa&#231;&#227;o a neoplasias em doentes com SM num seguimento a longo&#8208;prazo&#44; ao contr&#225;rio do anteriormente reportado por outros estudos&#46;</p><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Limita&#231;&#245;es</span><p id="par0195" class="elsevierStylePara elsevierViewall">A principal limita&#231;&#227;o do estudo relaciona&#8208;se com o facto de a dimens&#227;o da amostra para o tempo de seguimento ser relativamente pequena e o n&#250;mero de eventos observados foi tamb&#233;m pequeno&#44; n&#227;o tendo poder estat&#237;stico para confirmar o impacto que tendencialmente &#233; aparente nos resultados apresentados&#46; Este facto n&#227;o permite tamb&#233;m realizar an&#225;lises mais detalhadas da influ&#234;ncia de cada componente da SM na ocorr&#234;ncia de eventos cardiovasculares&#46; Contudo&#44; os dados apresentados abrem uma janela de oportunidade para estudos mais alargados&#46;</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Conclus&#227;o</span><p id="par0200" class="elsevierStylePara elsevierViewall">Num seguimento a longo&#8208;prazo&#44; a presen&#231;a de doen&#231;a coron&#225;ria teve um impacto muito importante na ocorr&#234;ncia de eventos&#44; mas n&#227;o a presen&#231;a de SM&#44; questionando o impacto da obesidade e da SM em preven&#231;&#227;o secund&#225;ria&#46; Contudo&#44; ser&#225; necess&#225;ria uma an&#225;lise numa popula&#231;&#227;o de maiores dimens&#245;es e eventualmente com maior seguimento e maior n&#250;mero de eventos para se obterem conclus&#245;es mais definitivas&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Conflitos de interesse</span><p id="par0205" class="elsevierStylePara elsevierViewall">Os autores declaram n&#227;o haver conflitos de interesse&#46;</p></span></span>"
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          "palabras" => array:4 [
            0 => "S&#237;ndrome metab&#243;lica"
            1 => "Doen&#231;a coron&#225;ria"
            2 => "Eventos cardiovasculares"
            3 => "Progn&#243;stico"
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          "palabras" => array:4 [
            0 => "Metabolic syndrome"
            1 => "Coronary artery disease"
            2 => "Cardiovascular events"
            3 => "Prognosis"
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    "resumen" => array:2 [
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introdu&#231;&#227;o</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Doentes com obesidade t&#234;m um maior risco de eventos cardiovasculares em preven&#231;&#227;o prim&#225;ria&#46; Em preven&#231;&#227;o secund&#225;ria tem sido descrito um paradoxo da obesidade&#46; Foi nosso objetivo estudar uma coorte de indiv&#237;duos analisados previamente num estudo transversal sobre a rela&#231;&#227;o entre s&#237;ndrome metab&#243;lica &#40;SM&#41; e doen&#231;a coron&#225;ria &#40;DC&#41;&#44; estudando presentemente o impacto da SM na ocorr&#234;ncia de eventos cardiovasculares a longo&#8208;prazo&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">M&#233;todos</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Foram analisados 296 indiv&#237;duos num seguimento m&#233;dio de 6&#44;9 &#177; 2&#44;2 anos&#46; Os indiv&#237;duos foram divididos em quatro grupos em fun&#231;&#227;o da presen&#231;a ou aus&#234;ncia de SM e de DC &#40;estenoses coron&#225;rias &#8805; 70&#37;&#41;&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Resultados</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">A popula&#231;&#227;o analisada tinha uma idade de 65 &#177; 9 anos no in&#237;cio do estudo&#44; 59&#44;5&#37; do sexo masculino&#44; 55&#44;7&#37; com SM e 41&#44;6&#37; com DC&#46; No seguimento&#44; ocorreram 10&#44;1&#37; de mortes por todas as causas&#44; 3&#44;7&#37; mortes cardiovasculares&#44; 14&#44;2&#37; reinternamentos cardiovasculares e 22&#44;0&#37; de eventos compostos &#40;morte&#44; s&#237;ndrome coron&#225;ria aguda&#44; revasculariza&#231;&#227;o coron&#225;ria&#44; acidente vascular cerebral&#47;isqu&#233;mico transit&#243;rio&#44; admiss&#227;o por insufici&#234;ncia card&#237;aca&#41;&#46; N&#227;o se verificaram diferen&#231;as significativas em termos de mortalidade&#46; Ambos os grupos com DC tiveram mais reinternamentos e eventos compostos &#40;Log&#8208;<span class="elsevierStyleItalic">rank</span>&#44; p &#60; 0&#44;001 e p &#61; 0&#44;001&#44; respetivamente&#41;&#44; mas sem diferen&#231;as em rela&#231;&#227;o &#224; presen&#231;a de SM&#46; A DC foi preditora independente de reinternamento cardiovascular &#40;HR 3&#44;21&#44; IC 95&#37; 1&#44;66&#8211;6&#44;21&#41; e de eventos compostos &#40;HR 2&#44;41&#44; IC 95&#37; 1&#44;44&#8211;4&#44;02&#41;&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclus&#245;es</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Em doentes de elevado risco cardiovascular ou com doen&#231;a coron&#225;ria estabelecida&#44; a presen&#231;a de SM n&#227;o se associou a aumento de eventos cerebrais ou card&#237;acos num seguimento a longo&#8208;prazo&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Introdu&#231;&#227;o"
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          1 => array:2 [
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            "titulo" => "M&#233;todos"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introduction</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Obese patients are at higher cardiovascular risk in primary prevention&#46; In secondary prevention&#44; an obesity paradox has been reported&#46; We analyzed a cohort of individuals from a previous cross&#8208;sectional study on the impact of metabolic syndrome &#40;MS&#41; on coronary artery disease &#40;CAD&#41;&#44; aiming to assess the occurrence of cardiovascular events in a long follow&#8208;up&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Methods</span><p id="spar0105" class="elsevierStyleSimplePara elsevierViewall">We analyzed 296 individuals in a mean follow&#8208;up of 6&#46;9&#177;2&#46;2 years&#46; Subjects were divided into four groups according to the presence of MS or CAD &#40;defined as &#8805;70&#37; coronary stenosis&#41;&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Results</span><p id="spar0110" class="elsevierStyleSimplePara elsevierViewall">The study population had a mean age of 65&#177;9 years at the beginning of the study&#59; 59&#46;5&#37; were male&#44; 55&#46;7&#37; had MS and 41&#46;6&#37; had CAD&#46; During follow&#8208;up 10&#46;1&#37; of the population suffered all&#8208;cause death&#44; 3&#46;7&#37; cardiovascular death&#44; 14&#46;2&#37; cardiovascular readmission and 22&#46;0&#37; the composite outcome &#40;mortality&#44; acute coronary syndrome&#44; coronary revascularization&#44; stroke&#47;transient ischemic attack or heart failure admission&#41;&#46; There were no significant differences in any type of mortality&#46; Patients with CAD had more readmissions and composite outcomes &#40;log&#8208;rank p&#60;0&#46;001 and p&#61;0&#46;001&#44; respectively&#41;&#44; but there was no difference according to the presence of MS&#46; Only CAD was an independent predictor of cardiovascular admission &#40;HR 3&#46;21&#44; 95&#37; CI 1&#46;66&#8208;6&#46;21&#41; and composite outcomes &#40;HR 2&#46;41&#44; 95&#37; CI 1&#46;44&#8208;4&#46;02&#41;&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusions</span><p id="spar0115" class="elsevierStyleSimplePara elsevierViewall">In patients with high cardiovascular risk or established CAD&#44; the presence of MS is not associated with cerebral or cardiac events in long&#8208;term follow&#8208;up&#46;</p></span>"
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">HR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">IC 95&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">p&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Mortalidade de todas as causas</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>S&#237;ndrome metab&#243;lica&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;56&#8211;2&#44;52&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;652&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Doen&#231;a coron&#225;ria&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;54&#8211;2&#44;42&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;672&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Mortalidade cardiovascular</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>S&#237;ndrome metab&#243;lica&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;81&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;25&#8211;2&#44;67&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;730&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Doen&#231;a coron&#225;ria&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;45&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;44&#8211;4&#44;79&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;545&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Admiss&#227;o cardiovascular</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>S&#237;ndrome metab&#243;lica&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;93&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;50&#8211;1&#44;73&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;818&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Doen&#231;a coron&#225;ria&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">3&#44;21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;66&#8211;6&#44;21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#44;001&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t  " colspan="4" align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Eventos compostos</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>S&#237;ndrome metab&#243;lica&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;03&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;61&#8211;1&#44;74&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;901&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Doen&#231;a coron&#225;ria&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#44;41&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#44;44&#8211;4&#44;02&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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        "descripcion" => array:1 [
          "pt" => "<p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">An&#225;lise multivariada de Cox sobre efeito preditor da s&#237;ndrome metab&#243;lica e&#47;ou doen&#231;a coron&#225;ria na ocorr&#234;ncia de eventos</p>"
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      "titulo" => "Refer&#234;ncias"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0015"
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            0 => array:3 [
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              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Cardiovascular diseases in Europe&#58; epidemiological update 2016"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "N&#46; Townsend"
                            1 => "L&#46; Wilson"
                            2 => "P&#46; Bhatnagar"
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                    0 => array:2 [
                      "doi" => "10.1093/eurheartj/ehw334"
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur Heart J&#46;"
                        "fecha" => "2016"
                        "volumen" => "37"
                        "paginaInicial" => "3232"
                        "paginaFinal" => "3245"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27523477"
                            "web" => "Medline"
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              "identificador" => "bib0160"
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              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "Programa Nacional para as doen&#231;as c&#233;rebro&#8208;cardiovasculares 2017&#46; Ed&#46; Dire&#231;&#227;o Geral Sa&#250;de&#44; Lisboa&#44; Setembro 2017&#44; p&#225;gina 5&#46;"
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            2 => array:3 [
              "identificador" => "bib0165"
              "etiqueta" => "3"
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                0 => array:1 [
                  "referenciaCompleta" => "Causas de Morte 2015&#46; Ed&#46; Instituto Nacional de Estat&#237;stica&#44; I&#46;P&#46;&#44; Lisboa&#44; Maio 2017&#44; p&#225;ginas 31 e 96&#46;"
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            3 => array:3 [
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Metabolic syndrome and risk of cardiovascular disease&#58; a meta&#8208;analysis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "A&#46; Galassi"
                            1 => "K&#46; Reynolds"
                            2 => "J&#46; He"
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                      ]
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                    0 => array:2 [
                      "doi" => "10.1016/j.amjmed.2006.02.031"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Med&#46;"
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                        "volumen" => "119"
                        "paginaInicial" => "812"
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                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17000207"
                            "web" => "Medline"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Metabolic syndrome and risk of incident cardiovascular events and death&#58; a systematic review and meta&#8208;analysis of longitudinal studies"
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                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "A&#46;S&#46; Gami"
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                            2 => "D&#46;E&#46; Howard"
                          ]
                        ]
                      ]
                    ]
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                    0 => array:2 [
                      "doi" => "10.1016/j.jacc.2006.09.032"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Am Coll Cardiol&#46;"
                        "fecha" => "2007"
                        "volumen" => "49"
                        "paginaInicial" => "403"
                        "paginaFinal" => "414"
                        "link" => array:1 [
                          0 => array:2 [
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                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The metabolic syndrome and cardiovascular risk&#58; a systematic review and meta&#8208;analysis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:3 [
                            0 => "S&#46; Motillo"
                            1 => "K&#46;B&#46; Filion"
                            2 => "J&#46; Genest"
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                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jacc.2010.05.034"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Am Coll Cardiol&#46;"
                        "fecha" => "2010"
                        "volumen" => "56"
                        "paginaInicial" => "1113"
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                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20863953"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Metabolic syndrome &#40;MetS&#41; predicts cardio and cerebrovascular events in a twenty years follow&#8208;up&#46; A prospective study"
                      "autores" => array:1 [
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                          "etal" => true
                          "autores" => array:3 [
                            0 => "S&#46; Novo"
                            1 => "A&#46; Peritore"
                            2 => "F&#46;P&#46; Guameri"
                          ]
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                    ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.atherosclerosis.2012.05.018"
                      "Revista" => array:6 [
                        "tituloSerie" => "Atherosclerosis&#46;"
                        "fecha" => "2012"
                        "volumen" => "223"
                        "paginaInicial" => "468"
                        "paginaFinal" => "472"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22704563"
                            "web" => "Medline"
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                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "&#40;em nome dos investigadores do estudo VALSIM&#41; S&#237;ndrome Metab&#243;lica em Portugal&#58; Preval&#234;ncia e Implica&#231;&#245;es no Risco Cardiovascular &#8211; Resultados do Estudo VALSIM"
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                          "etal" => true
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                            0 => "M&#46; Fi&#250;za"
                            1 => "N&#46; Cortez-Dias"
                            2 => "S&#46; Martins"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Rev Port Cardiol&#46;"
                        "fecha" => "2008"
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