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  <front>
    <journal-meta>
      <journal-id journal-id-type="nlm-ta">Arq Bras Cardiol</journal-id>
      <journal-title-group>
        <journal-title>Arquivos Brasileiros de Cardiologia</journal-title>
        <abbrev-journal-title abbrev-type="publisher">Arq. Bras. Cardiol.</abbrev-journal-title>
      </journal-title-group>
      <issn pub-type="ppub">0066-782X</issn>
      <issn pub-type="epub">1678-4170</issn>
      <publisher>
        <publisher-name>Sociedade Brasileira de Cardiologia</publisher-name>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v3">38Vph5VkwLFnR4BJd4X4B7Q</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v2">S0066-782X2014000300017</article-id>
      <article-id pub-id-type="other">00017</article-id>
      <article-id pub-id-type="doi">10.5935/abc.20140025</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Ponto De Vista</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title xml:lang="pt">Manifesta&#231;&#227;o At&#237;pica da Isquemia Mioc&#225;rdica no
               Idoso</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Ochiai</surname>
            <given-names>Marcelo E.</given-names>
          </name>
          <xref ref-type="corresp" rid="c01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Lopes</surname>
            <given-names>Neusa Helena</given-names>
          </name>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Buzo</surname>
            <given-names>Carolina Giusti</given-names>
          </name>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Pierri</surname>
            <given-names>Humberto</given-names>
          </name>
        </contrib>
        <aff>
          <institution content-type="orgname">USP</institution>
          <institution content-type="orgdiv1">Faculdade de Medicina</institution>
          <institution content-type="orgdiv2">Hospital das Cl&#237;nicas</institution>
          <institution content-type="orgdiv3">Instituto do Cora&#231;&#227;o</institution>
          <addr-line>
            <named-content content-type="city">S&#227;o Paulo</named-content>
            <named-content content-type="state">SP</named-content>
          </addr-line>
          <country>Brasil</country>
          <institution content-type="original">Instituto do Cora&#231;&#227;o (InCor) - Hospital das
                  Cl&#237;nicas da Faculdade de Medicina da USP, S&#227;o Paulo, SP - Brasil</institution>
        </aff>
      </contrib-group>
      <author-notes>
        <corresp id="c01"><bold>Correspond&#234;ncia: Marcelo E. Ochiai</bold>, Av. En&#233;as de Carvalho Aguiar, 44,
               Bloco II, 2&#186; andar, S&#227;o Paulo, SP- Brasil. E-mail:
                  <email>Marcelo.ochiai@incor.usp.br</email>
				</corresp>
        <fn fn-type="con">
          <p>
            <bold>Contribui&#231;&#227;o dos autores</bold>
          </p>
          <p>Concep&#231;&#227;o e desenho da pesquisa: Ochiai ME, Lopes NH, Buzo CG, Pierri H; Obten&#231;&#227;o
                  de dados e Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do intelectual: Ochiai
                  ME, Lopes NH, Pierri H; Reda&#231;&#227;o do manuscrito: Ochiai ME, Buzo CG, Pierri H.</p>
        </fn>
        <fn fn-type="conflict">
          <p>
            <bold>Potencial Conflito de Interesses</bold>
          </p>
          <p>Declaro n&#227;o haver conflito de interesses pertinentes</p>
        </fn>
      </author-notes>
      <pub-date pub-type="epub-ppub">
        <month>03</month>
        <year>2014</year>
      </pub-date>
      <volume>102</volume>
      <issue>3</issue>
      <elocation-id>31</elocation-id>
      <history>
        <date date-type="received">
          <day>13</day>
          <month>05</month>
          <year>2013</year>
        </date>
        <date date-type="rev-recd">
          <day>22</day>
          <month>08</month>
          <year>2013</year>
        </date>
        <date date-type="accepted">
          <day>18</day>
          <month>10</month>
          <year>2013</year>
        </date>
      </history>
      <kwd-group xml:lang="pt">
        <kwd>Isquemia mioc&#225;rdica / fisiopatologia</kwd>
        <kwd>Idoso</kwd>
        <kwd>Insufici&#234;ncia card&#237;aca</kwd>
        <kwd>Doen&#231;a da art&#233;ria coronariana</kwd>
        <kwd>Angina pectoris</kwd>
      </kwd-group>
      <counts>
        <fig-count count="1"/>
        <table-count count="0"/>
        <equation-count count="0"/>
        <ref-count count="15"/>
        <page-count count="3"/>
      </counts>
    </article-meta>
  </front>
  <body>
    <p>Frequentemente, pacientes mais velhos apresentam quadro cl&#237;nico at&#237;pico para isquemia
         mioc&#225;rdica ou s&#227;o assintom&#225;ticos. A presente revis&#227;o pretende reexaminar a fisiopatologia
         da manifesta&#231;&#227;o at&#237;pica no idoso, suas implica&#231;&#245;es progn&#243;sticas e terap&#234;uticas.</p>
    <p>A doen&#231;a ateroscler&#243;tica coronariana &#233; um problema crescente de sa&#250;de p&#250;blica, de especial
         import&#226;ncia nas faixas et&#225;rias mais elevadas. A sua preval&#234;ncia aumenta significamente a
         partir da sexta d&#233;cada de vida, tornando-se a maior causa de morte para as pessoas mais
         velhas, bem como a maior respons&#225;vel pela interna&#231;&#227;o hospitalar e procedimentos
            invasivos<xref ref-type="bibr" rid="B01">1</xref>.</p>
    <p>No idoso, a manifesta&#231;&#227;o cl&#237;nica ausente ou at&#237;pica dificulta o manejo da doen&#231;a
         ateroscler&#243;tica coronariana. A situa&#231;&#227;o de ocorr&#234;ncia de isquemia mioc&#225;rdica sem dor, a
         chamada isquemia assintom&#225;tica ou silenciosa, &#233; mais frequente no paciente idoso<xref ref-type="bibr" rid="B02">2</xref>. Considerando pacientes com s&#237;ndrome coronariana
         aguda, como infarto do mioc&#225;rdio com supradesnivelamento do segmento ST, entre aqueles com
         menos de 65 anos de idade, somente 11,1% n&#227;o apresentam dor precordial, diferentemente
         daqueles com mais de 85 anos de idade, entre os quais 43,2% n&#227;o apresentam dor
            precordial<xref ref-type="bibr" rid="B03">3</xref>. Similarmente, entre os pacientes
         idosos que apresentam onda Q no eletrocardiograma (ECG), 78% n&#227;o haviam tido sintoma de dor
            precordial<xref ref-type="bibr" rid="B04">4</xref>(<xref ref-type="fig" rid="f01">Figura
            1</xref>).</p>
    <fig id="f01" fig-type="other">
      <label>Figura 1</label>
      <caption>
        <title>Apresenta&#231;&#227;o cl&#237;nica do infarto agudo do mioc&#225;rdio segundo a idade. Bayer AJ,
               Chadha JS, Farag RR, Pathy MS. J Am Geriatr Soc. 1986; 34:263-6.</title>
      </caption>
      <graphic xlink:href="1678-4170-abc-102-03-0031-40025-gf01.jpg"/></fig>
    <p>O diabetes melito tem sido considerado o maior fator relacionado &#224; isquemia assintom&#225;tica
         em paciente com doen&#231;a coronariana est&#225;vel, entretanto diversos estudos n&#227;o encontraram
         essa associa&#231;&#227;o<xref ref-type="bibr" rid="B05">5</xref>. Esses mesmos estudos indicam que o
         &#250;nico fator independente para isquemia silenciosa &#233; a idade avan&#231;ada. De fato, ocorre
         aumento progressivo no intervalo entre o in&#237;cio do infradesnivelamento do segmento ST e o
         in&#237;cio da angina com o aumento da idade<xref ref-type="bibr" rid="B06">6</xref>, indicando
         aumento do limiar de dor entre os mais velhos.</p>
    <p>Quando ocorre um epis&#243;dio de redu&#231;&#227;o do fluxo sangu&#237;neo coronariano, a primeira altera&#231;&#227;o &#233;
         o sofrimento do mi&#243;cito, seguindo-se altera&#231;&#227;o de relaxamento mioc&#225;rdico e
         infradesnivelamento do segmento ST. A dor &#233; a &#250;ltima manifesta&#231;&#227;o da isquemia
            mioc&#225;rdica<xref ref-type="bibr" rid="B07">7</xref>.</p>
    <p>A maior preval&#234;ncia de isquemia mioc&#225;rdica assintom&#225;tica ou com sintomas at&#237;picos nos
         idosos &#233; explicada pelo maior limiar de dor relacionado &#224;s altera&#231;&#245;es nociceptivas e pela
         grande preval&#234;ncia de doen&#231;as como depress&#227;o e diabetes melito. Aumento do n&#237;vel s&#233;rico de
         beta-endorfinas tamb&#233;m tem sido descrito nos pacientes com isquemia mioc&#225;rdica
            assintom&#225;tica<xref ref-type="bibr" rid="B08">8</xref>, entretanto existem estudos com
         achados diferentes<xref ref-type="bibr" rid="B09">9</xref>
			<sup>,</sup>
			<xref ref-type="bibr" rid="B10">10</xref>.Adicionalmente, pacientes com isquemia silenciosa apresentam
         ativa&#231;&#227;o nervosa central diferente daqueles com angina quando submetidos a estresse
         isqu&#234;mico com dobutamina, predominando a ativa&#231;&#227;o dos c&#243;rtex frontal, ventral e
            temporal<xref ref-type="bibr" rid="B11">11</xref>.Curiosamente, a &#225;rea tal&#226;mica, que &#233; a
         respons&#225;vel pelo reconhecimento da dor, teve ativa&#231;&#227;o semelhante entre os pacientes com e
         sem angina<xref ref-type="bibr" rid="B12">12</xref>.</p>
    <p>Por outro lado, os pacientes idosos apresentam comorbidades que podem influenciar na
         manifesta&#231;&#227;o cl&#237;nica da isquemia mioc&#225;rdica. Mesmo o diabetes melito &#233; uma condi&#231;&#227;o cuja
         preval&#234;ncia aumenta com a idade, assim como a neuropatia diab&#233;tica.</p>
    <p>A fibromialgia e a depress&#227;o s&#227;o condi&#231;&#245;es neuropsiqui&#225;tricas que interferem na sensa&#231;&#227;o
         dolorosa. Por vezes, idosos com queixa de dor precordial, com o diagn&#243;stico de isquemia
         mioc&#225;rdica descartado, melhoram com o uso de antidepressivos. O contr&#225;rio tamb&#233;m pode
         ocorrer, com idosos com dor at&#237;pica para isquemia mioc&#225;rdica, geralmente atribu&#237;da &#224;
         depress&#227;o, terem doen&#231;a coronariana significativa. A rela&#231;&#227;o entre depress&#227;o e doen&#231;a
         coronariana ateroscler&#243;tica est&#225; bem definida<xref ref-type="bibr" rid="B13">13</xref>,entretanto s&#227;o v&#225;rias as raz&#245;es pelas quais a depress&#227;o aumenta a ocorr&#234;ncia da
         coronariopatia. Pacientes com depress&#227;o apresentam menor ader&#234;ncia ao tratamento
         medicamentoso e mudan&#231;as de estilo de vida. Adicionalmente,a depress&#227;o<xref ref-type="bibr" rid="B14">14</xref> pode causar altera&#231;&#227;o da fun&#231;&#227;o endotelial, desregula&#231;&#227;o do eixo
         hipot&#225;lamo-hip&#243;fise-adrenal, aumento da reatividade plaquet&#225;ria e marcadores inflamat&#243;rios
         com a interleucina 6.</p>
    <p>Altera&#231;&#245;es de mem&#243;ria, que s&#227;o frequentes nos pacientes idosos, como a doen&#231;a de Alzheimer
         e a dem&#234;ncia vascular, t&#234;m como caracter&#237;stica a perda da mem&#243;ria recente.
         Consequentemente, nesses pacientes, o relato confi&#225;vel de sintomas de in&#237;cio recente &#233;
         prejudicado. Tanto a doen&#231;a de Alzheimer como a dem&#234;ncia vascular t&#234;m fatores de risco
         semelhantes aos da doen&#231;a coronariana. Dessa forma, al&#233;m da concomit&#226;ncia frequente, o
         d&#233;ficit de mem&#243;ria leva o idoso &#224; dificuldade de lembrar e descrever adequadamente a dor
         decorrente da isquemia mioc&#225;rdica.</p>
    <p>Entre os idosos portadores de insufici&#234;ncia card&#237;aca, 50-70% apresentam a isquemia
         mioc&#225;rdica como etiologia, e parte consider&#225;vel deles tem revasculariza&#231;&#227;o do mioc&#225;rdio
         pr&#233;via. Tanto a insufici&#234;ncia card&#237;aca<xref ref-type="bibr" rid="B15">15</xref> como a
         revasculariza&#231;&#227;o do mioc&#225;rdio reduzem o desempenho cognitivo, principalmente no dom&#237;nio de
         aten&#231;&#227;o. Dessa forma, caso o paciente apresente isquemia mioc&#225;rdica, esse d&#233;ficit cognitivo
         pode prejudicar o relato das caracter&#237;sticas da dor. </p>
    <p>Concluindo, os pacientes idosos com isquemia mioc&#225;rdica frequentemente apresentam
         manifesta&#231;&#245;es cl&#237;nicas at&#237;picas, devido a comorbidades como diabetes melito, altera&#231;&#245;es
         nociceptivas, depress&#227;o e dem&#234;ncia. Portanto, nos pacientes idosos, os sintomas at&#237;picos
         para insufici&#234;ncia coronariana devem ser valorizados, e, para a confirma&#231;&#227;o ou n&#227;o do
         diagn&#243;stico de isquemia mioc&#225;rdica, a pesquisa atrav&#233;s de exames complementares deve ser
         mais rigorosa. Adicionalmente, esses exames de pesquisa de isquemia mioc&#225;rdica tamb&#233;m
         identificam os pacientes de maior risco, que devem ser tratados de forma mais
         intensiva.</p>
  </body>
  <back>
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    <fn-group>
      <fn fn-type="supported-by">
        <p>
          <bold>Fontes de Financiamento</bold>
        </p>
        <p>O presente estudo n&#227;o teve fontes de financiamento externas</p>
      </fn>
      <fn fn-type="other">
        <p>
          <bold>Vincula&#231;&#227;o Acad&#234;mica</bold>
        </p>
        <p>N&#227;o h&#225; vincula&#231;&#227;o desse estudo a programas de p&#243;s-gradua&#231;&#227;o.</p>
      </fn>
    </fn-group>
  </back>
  <sub-article article-type="translation" id="SA1" xml:lang="en">
    <front-stub>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Viewpoint</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title xml:lang="en">Atypical Manifestation of Myocardial Ischemia in the
               Elderly</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Ochiai</surname>
            <given-names>Marcelo E.</given-names>
          </name>
          <xref ref-type="corresp" rid="c02"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Lopes</surname>
            <given-names>Neusa Helena</given-names>
          </name>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Buzo</surname>
            <given-names>Carolina Giusti</given-names>
          </name>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Pierri</surname>
            <given-names>Humberto</given-names>
          </name>
        </contrib>
        <aff>
          <institution content-type="orgname">USP</institution>
          <institution content-type="orgdiv1">Faculdade de Medicina</institution>
          <institution content-type="orgdiv2">Hospital das Cl&#237;nicas</institution>
          <institution content-type="orgdiv3">Instituto do Cora&#231;&#227;o</institution>
          <addr-line>
            <named-content content-type="city">S&#227;o Paulo</named-content>
            <named-content content-type="state">SP</named-content>
          </addr-line>
          <country>Brazil</country>
          <institution content-type="original">Instituto do Cora&#231;&#227;o (InCor) - Hospital das
                  Cl&#237;nicas da Faculdade de Medicina da USP, S&#227;o Paulo, SP - Brazil</institution>
        </aff>
      </contrib-group>
      <author-notes>
        <corresp id="c02"><bold>Mailing: Marcelo E. Ochiai,</bold> Av. En&#233;as de Carvalho Aguiar, 44, Bloco II,
               2.&#186; andar, S&#227;o Paulo, SP - Brazil. E-mail: <email>Marcelo.ochiai@incor.usp.br</email>
				</corresp>
        <fn fn-type="con">
          <p>
            <bold>Author contributions</bold>
          </p>
          <p>Conception and design of the research: Ochiai ME, Lopes NH, Buzo CG, Pierri H;
                  Acquisition of data and Critical revision of the manuscript for intellectual
                  content: Ochiai ME, Lopes NH, Pierri H; Writing of the manuscript: Ochiai ME, Buzo
                  CG, Pierri H.</p>
        </fn>
        <fn fn-type="conflict">
          <p>
            <bold>Potential Conflict of Interest</bold>
          </p>
          <p>No potential conflict of interest relevant to this article was reported.</p>
        </fn>
      </author-notes>
      <kwd-group xml:lang="en">
        <kwd>Myocardial Ischemia / physiopathology</kwd>
        <kwd>Aged</kwd>
        <kwd>Heart Failure</kwd>
        <kwd>Coronary Artery Disease</kwd>
        <kwd>Angina Pectoris</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <p>Often, elderly patients have atypical clinical picture for myocardial ischemia, or are
            asymptomatic. This review intends to re-examine the pathophysiology of atypical
            manifestation in elderly persons, its prognostic and therapeutic implications.</p>
      <p>The coronary atherosclerotic disease is an increasing public health problem, of
            particular importance in higher age groups. Its prevalence increases significantly at
            the sixth decade of life, becoming the leading cause of death in older people, as well
            as the greatest responsible for hospitalization and invasive procedures<xref ref-type="bibr" rid="B01">1</xref>.</p>
      <p>The absent or atypical clinical signs in elderly persons hinder the management of
            coronary atherosclerotic disease. The cases of myocardial ischemia without pain, the
            so-called asymptomatic or silent ischemia, it is more frequent in elderly patient<xref ref-type="bibr" rid="B02">2</xref>. Considering patients with acute coronary
            syndrome, as myocardial infarction with ST-segment elevation, among those under 65 years
            of age, only 11.1% do not have precordial pain, unlike those over 85 years old, among
            which 43.2% have precordial pain<xref ref-type="bibr" rid="B03">3</xref>. Similarly,
            among elderly patients with Q wave in electrocardiogram (ECG), 78% did not have symptoms
            of precordial pain<xref ref-type="bibr" rid="B04">4</xref> (<xref ref-type="fig" rid="f02">Figure 1</xref>).</p>
      <fig id="f02" fig-type="other">
        <label>Figure 1</label>
        <caption>
          <title>Clinical presentation of acute myocardial infarction according to age. Bayer
                  AJ, Chadha JS, Farag RR, Pathy MS. J Am Geriatr Soc. 1986; 34:263-6.</title>
        </caption>
        <graphic xlink:href="1678-4170-abc-102-03-0031-40025-gf01-en.jpg"/></fig>
      <p>Diabetes mellitus has been considered the biggest factor related to asymptomatic
            ischemia in patients with stable coronary disease. However, several studies found no
            such association<xref ref-type="bibr" rid="B05">5</xref>. These studies indicate that
            the only independent factor for silent ischemia is advanced age. In fact, progressive
            increase occurs in the interval between the beginning of ST segment depression and the
            onset of angina with increased age<xref ref-type="bibr" rid="B06">6</xref>, indicating
            increased pain threshold among elderly.</p>
      <p>When an episode of coronary blood flow reduction occurs, the first alteration is the
            suffering of myocyte, following changes of myocardial relaxation and ST segment
            depression. Pain is the last manifestation of myocardial ischemia<xref ref-type="bibr" rid="B07">7</xref>.</p>
      <p>The higher prevalence of asymptomatic myocardial ischemia or with atypical symptoms in
            elderly is explained by increased pain threshold related to nociceptive changes and by
            the great prevalence of diseases such as depression and diabetes mellitus. Increased
            beta-endorphins levels have also been described in patients with asymptomatic myocardial
               ischemia<xref ref-type="bibr" rid="B08">8</xref>. However, there are studies with
            different findings<xref ref-type="bibr" rid="B09">9</xref>
				<sup>,</sup>
				<xref ref-type="bibr" rid="B10">10</xref>. Additionally, patients suffering from silent
            ischemia have central nervous activation different from those with angina when subjected
            to ischemic dobutamine stress, predominating the frontal cortex and ventral temporal
               activation<xref ref-type="bibr" rid="B11">11</xref>. Interestingly, the thalamic
            area, which is responsible for the recognition of pain, had similar activation in
            patients with and without angina<xref ref-type="bibr" rid="B12">12</xref>.</p>
      <p>On the other hand, the elderly patients have comorbidities that may influence the
            clinical manifestation of myocardial ischemia. Even the diabetes mellitus is a condition
            whose prevalence increases with age, as well as diabetic neuropathy.</p>
      <p>Fibromyalgia and depression are neuropsychiatric conditions that interfere with the
            painful sensation. Sometimes, elderly persons complain of precordial pain, with rejected
            diagnosis of myocardial ischemia, improve with antidepressants. The opposite can also
            occur, with elderly people with atypical pain for myocardial ischemia, generally
            attributed to depression, having significant coronary disease. The relationship between
            depression and coronary atherosclerotic disease is well defined<xref ref-type="bibr" rid="B13">13</xref>. However, there are several reasons why depression increases the
            occurrence of coronary disease. Patients with depression have less treatment adherence
            to drug and lifestyle changes. Additionally, depression<xref ref-type="bibr" rid="B14">14</xref> can cause change of endothelial function, deregulation of the
            hypothalamic-pituitary-adrenal axis, increased platelet reactivity and inflammatory
            markers with interleukin 6.</p>
      <p>Memory changes, which are frequent in elderly patients, as Alzheimer's disease and
            vascular dementia, are characterized by the loss of short term memory. Consequently, in
            these patients, the reliable reporting of symptoms of recent onset is affected. Both
            Alzheimer's disease and vascular dementia have risk factors similar to those of coronary
            disease. As a result, besides frequent concomitance, memory deficit causes elderly to
            have memorization difficulty and describe the pain resulting from myocardial
            ischemia.</p>
      <p>Among elderly patients with heart failure, 50-70% have myocardial ischemia as etiology,
            and considerable part of them have prior myocardial revascularization. Both heart
               failure<xref ref-type="bibr" rid="B15">15</xref> and myocardial revascularization
            reduce cognitive performance, especially in the field of attention. Thus, if a patient
            has myocardial ischemia, this cognitive deficit can impair description of the pain
            characteristics.</p>
      <p>In conclusion, elderly patients with myocardial ischemia often have atypical clinical
            manifestations, due to comorbidities as diabetes mellitus, nociceptive changes,
            depression and dementia. Therefore, in elderly patients, atypical symptoms of coronary
            insufficiency should be valued, and to confirm or not diagnosis of myocardial ischemia,
            the search through additional tests should be more rigorous. Additionally, these
            research tests on myocardial ischemia also identify patients at higher risk that should
            be treated more intensively.</p>
    </body>
    <back>
      <fn-group>
        <fn fn-type="supported-by">
          <p>
            <bold>Sources of Funding</bold>
          </p>
          <p>There were no external funding sources for this study.</p>
        </fn>
        <fn fn-type="other">
          <p>
            <bold>Study Association</bold>
          </p>
          <p>This study is not associated with any post-graduation program.</p>
        </fn>
      </fn-group>
    </back>
  </sub-article>
</article>
