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  <front>
    <journal-meta>
      <journal-id journal-id-type="nlm-ta">Arq Bras Cardiol</journal-id>
      <journal-id journal-id-type="publisher-id">abc</journal-id>
      <journal-title-group>
        <journal-title>Arquivos Brasileiros de Cardiologia</journal-title>
        <abbrev-journal-title abbrev-type="publisher">Arq. Bras. Cardiol.</abbrev-journal-title>
      </journal-title-group>
      <issn pub-type="ppub">0066-782X</issn>
      <issn pub-type="epub">1678-4170</issn>
      <publisher>
        <publisher-name>Sociedade Brasileira de Cardiologia - SBC</publisher-name>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id specific-use="scielo-v3" pub-id-type="publisher-id">dDY3rkjjDXyBwX8cL8XPgXb</article-id>
      <article-id specific-use="scielo-v2" pub-id-type="publisher-id">S0066-782X2020000800146</article-id>
      <article-id pub-id-type="publisher-id">abc.20200486</article-id>
      <article-id pub-id-type="doi">10.36660/abc.20200486</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Carta ao Editor</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>A Exist&#234;ncia Pr&#233;via de Doen&#231;as do Aparelho Circulat&#243;rio Acelera a Mortalidade por COVID-19?</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0003-2875-9863</contrib-id>
          <name>
            <surname>Souza</surname>
            <given-names>Carlos Dornels Freire de</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Leal</surname>
            <given-names>Thiago Cavalcanti</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Santos</surname>
            <given-names>Lucas Gomes</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
        </contrib>
      </contrib-group>
      <aff id="aff1">
        <label>1</label>
        <institution content-type="orgname">Universidade Federal de Alagoas</institution>
        <addr-line>
          <named-content content-type="city">Arapiraca</named-content>
          <named-content content-type="state">AL</named-content>
        </addr-line>
        <country country="BR">Brasil</country>
        <institution content-type="original">Universidade Federal de Alagoas - Campus Arapiraca, Arapiraca, AL - Brasil</institution>
      </aff>
      <author-notes>
        <corresp id="c01"><bold>Correspond&#234;ncia:</bold> Carlos Dornels Freire de Souza &#8226; Universidade Federal de Alagoas - Campus Arapiraca &#8211; Medicina &#8211; Av. Manoel Severino Barbosa, S/N. CEP 57309-005, Arapiraca, AL &#8211; Brasil E-mail: <email>carlos.freire@arapiraca.ufal.br</email> </corresp>
      </author-notes>
      <pub-date date-type="pub" publication-format="electronic">
        <day>07</day>
        <month>08</month>
        <year>2020</year>
      </pub-date>
      <pub-date date-type="collection" publication-format="electronic">
        <month>07</month>
        <year>2020</year>
      </pub-date>
      <volume>115</volume>
      <issue>1</issue>
      <fpage>146</fpage>
      <lpage>147</lpage>
      <history>
        <date date-type="received">
          <day>17</day>
          <month>05</month>
          <year>2020</year>
        </date>
        <date date-type="rev-recd">
          <day>21</day>
          <month>05</month>
          <year>2020</year>
        </date>
        <date date-type="accepted">
          <day>21</day>
          <month>05</month>
          <year>2020</year>
        </date>
      </history>
      <permissions>
        <license license-type="open-access" xlink:href="https://creativecommons.org/licenses/by/4.0/" xml:lang="en">
          <license-p> This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. </license-p>
        </license>
      </permissions>
      <kwd-group xml:lang="pt">
        <kwd>Coronavirus</kwd>
        <kwd>COVID-19</kwd>
        <kwd>Pandemia</kwd>
        <kwd>S&#237;ndrome Respirat&#243;ria Aguda Grave/complica&#231;&#245;es</kwd>
        <kwd>Comorbidades</kwd>
        <kwd>Fatores de Risco</kwd>
        <kwd>Diabetes</kwd>
        <kwd>Hipertens&#227;o</kwd>
        <kwd>Dispnea</kwd>
      </kwd-group>
      <counts>
        <fig-count count="2"/>
        <table-count count="0"/>
        <equation-count count="0"/>
        <ref-count count="6"/>
        <page-count count="2"/>
      </counts>
    </article-meta>
  </front>
  <body>
    <p>
      <bold>Caro Editor,</bold>
    </p>
    <p>Os primeiros casos de doen&#231;a de coronav&#237;rus 2019 (COVID-19) foram identificados na metr&#243;pole de Wuhan, capital da prov&#237;ncia de Hubei, na Rep&#250;blica Popular da China.<sup><xref ref-type="bibr" rid="B1">1</xref></sup> Nela, observou-se um surto de pneumonia de r&#225;pida progress&#227;o e de origem indeterminada associada &#224; exposi&#231;&#227;o comum ao mercado de frutos do mar da cidade.<sup><xref ref-type="bibr" rid="B1">1</xref></sup> Em 31 de dezembro de 2019, a China notificou o surto &#224; Organiza&#231;&#227;o Mundial da Sa&#250;de (OMS).<sup><xref ref-type="bibr" rid="B1">1</xref></sup> Um m&#234;s depois, em 30 de Janeiro, a OMS declarou situa&#231;&#227;o de emerg&#234;ncia internacional e, em 11 de mar&#231;o, foi declarada pandemia pela doen&#231;a.<sup><xref ref-type="bibr" rid="B2">2</xref></sup></p>
    <p>No Brasil, o primeiro caso foi confirmado em 26 de fevereiro de 2020, em S&#227;o Paulo. Em 17 de mar&#231;o, foi registrada a primeira morte no pa&#237;s e, tr&#234;s dias depois (20 de mar&#231;o), o Minist&#233;rio da Sa&#250;de reconheceu a transmiss&#227;o comunit&#225;ria em todo territ&#243;rio nacional. Em 15 de maio, o Brasil ocupava a sexta posi&#231;&#227;o mundial em casos acumulados, com mais de 200.000 infectados e mais de 13.000 mortes.<sup><xref ref-type="bibr" rid="B3">3</xref></sup></p>
    <p>Dentre os aspectos mais relevantes a serem observados no curso da pandemia s&#227;o os grupos de maior risco, dos quais se destacam os indiv&#237;duos com a idade superior a 60 anos e aqueles com comorbidades cardiovasculares como fatores de pior progn&#243;stico e maior letalidade quando infectados pelo novo coronav&#237;rus.<sup><xref ref-type="bibr" rid="B4">4</xref></sup></p>
    <p>Este estudo objetivou analisar a associa&#231;&#227;o entre a exist&#234;ncia pr&#233;via de doen&#231;as do aparelho circulat&#243;rio e o tempo (em dias) entre o in&#237;cio dos primeiros sintomas e a data do &#243;bito por COVID-19.</p>
    <p>Trata-se de um estudo de caso-controle envolvendo dados de 374 &#243;bitos por COVID-19 registrados no estado de Pernambuco. Os dados foram obtidos da p&#225;gina eletr&#244;nica de monitoramento da COVID-19 do estado (https://dados.seplag.pe.gov.br/apps/corona.html), em 07 de maio de 2020. Ap&#243;s a coleta, o banco de dados passou por ajustes das vari&#225;veis, que consistiu na avalia&#231;&#227;o dos sinais/sintomas e comorbidades. Ap&#243;s a adequa&#231;&#227;o, 197 indiv&#237;duos possu&#237;am doen&#231;a do aparelho circulat&#243;rio pr&#233;via, dos quais 187 apresentavam data do in&#237;cio dos sintomas e data do &#243;bito. Esses indiv&#237;duos compuseram o grupo de casos. Para a composi&#231;&#227;o do grupo controle, foram selecionados 187 &#243;bitos que n&#227;o possu&#237;am comorbidades relatadas. A sele&#231;&#227;o desses &#243;bitos foi aleat&#243;ria, obedecendo a data de in&#237;cio dos primeiros sintomas.</p>
    <p>No estudo, foram consideradas as seguintes vari&#225;veis: comorbidades existentes (nenhuma, uma, duas e tr&#234;s ou mais) e o tempo (em dias) entre a data dos primeiros sintomas e o &#243;bito por COVID-19. Para a an&#225;lise estat&#237;stica, foi utilizado o teste de Kolmogorov-Smirnov para a avalia&#231;&#227;o inicial da normalidade dos dados. Uma vez constatada a viola&#231;&#227;o do pressuposto de distribui&#231;&#227;o gaussiana, a associa&#231;&#227;o entre as vari&#225;veis foi avaliada pelo teste n&#227;o param&#233;trico U de Mann-Whitney. As an&#225;lises consideraram signific&#226;ncia de 5% e foram realizadas com o aux&#237;lio do software SPSS vers&#227;o 24.0 (IBM Corporation). Por utilizar dados de dom&#237;nio p&#250;blico, nos quais n&#227;o &#233; poss&#237;vel a identifica&#231;&#227;o dos indiv&#237;duos, este estudo dispensou a aprova&#231;&#227;o pelo Comit&#234; de &#201;tica em Pesquisa.</p>
    <p>A m&#233;dia e desvio-padr&#227;o (m&#233;dia &#177; DP) e mediana e intervalo interquartil (mediana &#8211; IIQ) de dias entre o in&#237;cio dos primeiros sintomas e a data do &#243;bito de toda a popula&#231;&#227;o do estudo (n = 374) foram 11,52 (&#177; 7,75) e 10 (IIQ 10), respectivamente. Do grupo casos, 38 (20,3%) possu&#237;am apenas uma doen&#231;a do aparelho circulat&#243;rio; 79 (42,2%) possu&#237;am duas comorbidades/fatores de risco e 70 (37,5%) possu&#237;am tr&#234;s ou mais comorbidades/fatores de risco. Salienta-se que pelo menos uma das comorbidades estava relacionada com o sistema circulat&#243;rio ( <xref ref-type="fig" rid="f01">Figura 1</xref> ).</p>
    <p>
      <fig id="f01">
        <label>Figura 1 </label>
        <caption>
          <title>&#8211; <italic>Compara&#231;&#227;o entre o n&#250;mero de dias entre o in&#237;cio dos primeiros sintomas e o &#243;bito por COVID-19, segundo presen&#231;a/aus&#234;ncia de comorbidades. Brasil, 2020.</italic></title>
        </caption>
        <graphic xlink:href="1678-4170-abc-115-01-0146-00486-gf01.tif"/></fig>
    </p>
    <p>Observou-se diferen&#231;a significativa entre o n&#250;mero de dias entre o in&#237;cio dos primeiros sintomas e o &#243;bito ao comparar os dois grupos. Os valores observados no grupo controle (m&#233;dia &#177; DP= 13,32 &#177; 7,2; mediana &#8211; IIQ= 11 &#8211; 11) foram superiores ao grupo que possu&#237;a comorbidades relatadas (m&#233;dia &#177; DP = 9,73 &#177; 7,8; mediana &#8211; IIQ = 7 &#8211; 9) ( <xref ref-type="fig" rid="f01">Figura 1</xref> ).</p>
    <p>O presente estudo aponta para uma progress&#227;o mais r&#225;pida da COVID-19 em quem possui comorbidades cardiovasculares, com uma m&#233;dia de dias do in&#237;cio dos primeiros sintomas ao &#243;bito inferior em quase quatro dias (3,9 dias na m&#233;dia e 4,0 na mediana), quando comparados o grupo que possu&#237;a enfermidades cardiovasculares pr&#233;vias e o grupo controle. Este processo decorre dos efeitos do SARS-CoV-2 no organismo humano, como a liga&#231;&#227;o do v&#237;rus &#224; enzima conversora de angiotensina 2 (ECA2) encontrada nas superf&#237;cies das c&#233;lulas card&#237;acas, renais e pulmonares.<sup><xref ref-type="bibr" rid="B4">4</xref></sup></p>
    <p>A exposi&#231;&#227;o das glicoprote&#237;nas relacionadas ao novo coronav&#237;rus &#224; ECA2 promove a sua internaliza&#231;&#227;o junto com o v&#237;rus, o que diminui a densidade de ECA2 na membrana<sup><xref ref-type="bibr" rid="B5">5</xref> , <xref ref-type="bibr" rid="B6">6</xref></sup> e consequentemente o efeito cardioprotetor relacionado &#224; hipertrofia card&#237;aca, &#224; fibrose mioc&#225;rdica e &#224; inflama&#231;&#227;o. Nesse sentido, associa-se a redu&#231;&#227;o de ECA2 &#224; exacerba&#231;&#227;o das cardiopatias existentes, tais como insufici&#234;ncia card&#237;aca e hipertens&#227;o arterial, contribuindo com a mais r&#225;pida progress&#227;o e o agravamento do quadro cl&#237;nico respirat&#243;rio e cardiovascular dos indiv&#237;duos com COVID-19.</p>
    <p>Com base nos resultados observados, a presen&#231;a de comorbidades cardiovasculares acelera a mortalidade por COVID-19. Ademias, outros estudos ainda devem ser realizados a fim de mensurar o impacto de cada doen&#231;a cardiovascular no risco de mortalidade.</p>
  </body>
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  </back>
  <sub-article article-type="translation" id="TRen" xml:lang="en">
    <front-stub>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Letter to the Editor</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Does Existence of Prior Circulatory System Diseases Accelerate Mortality Due to COVID-19?</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0003-2875-9863</contrib-id>
          <name>
            <surname>Souza</surname>
            <given-names>Carlos Dornels Freire de</given-names>
          </name>
          <xref ref-type="aff" rid="aff1001">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Leal</surname>
            <given-names>Thiago Cavalcanti</given-names>
          </name>
          <xref ref-type="aff" rid="aff1001">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Santos</surname>
            <given-names>Lucas Gomes</given-names>
          </name>
          <xref ref-type="aff" rid="aff1001">
            <sup>1</sup>
          </xref>
        </contrib>
      </contrib-group>
      <aff id="aff1001">
        <label>1</label>
        <country country="BR">Brazil</country>
        <institution content-type="original">Universidade Federal de Alagoas - Campus Arapiraca, Arapiraca, AL - Brazil</institution>
      </aff>
      <author-notes>
        <corresp id="c01001"><bold>Mailing Address:</bold> Carlos Dornels Freire de Souza &#8226; Universidade Federal de Alagoas - Campus Arapiraca &#8211; Medicina &#8211; Av. Manoel Severino Barbosa, S/N. Postal Code 57309-005, Arapiraca, AL &#8211; Brazil E-mail: carlos.freire@arapiraca.ufal.br</corresp>
      </author-notes>
      <kwd-group xml:lang="en">
        <kwd>Coronavirus, COVID-19, Pandemics</kwd>
        <kwd>Severe Acute Respiratory Syndrome/complications</kwd>
        <kwd>Comorbidity</kwd>
        <kwd>Risk Factors</kwd>
        <kwd>Diabetes</kwd>
        <kwd>Hypertension</kwd>
        <kwd>Dispnea</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <p>
        <bold>Dear Editor,</bold>
      </p>
      <p>The first cases of coronavirus disease 2019 (COVID-19) were identified in the metropolis of Wuhan, the capital of the province of Hubei, in the People&#8217;s Republic of China.<sup><xref ref-type="bibr" rid="B1">1</xref></sup> An outbreak of rapidly progressive pneumonia of undetermined origin associated with common exposure to the city&#8217;s seafood market was observed.<sup><xref ref-type="bibr" rid="B1">1</xref></sup> On December 31, 2019, China notified the World Health Organization (WHO) of the outbreak.<sup><xref ref-type="bibr" rid="B1">1</xref></sup> One month later, on January 30, 2020, the WHO declared the situation an international emergency, and, on March 11, the disease was declared a pandemic.<sup><xref ref-type="bibr" rid="B2">2</xref></sup></p>
      <p>In Brazil, the first case was confirmed on February 26, 2020, in S&#227;o Paulo. On March 17, the first death in the country was registered, and, three days later, on March 20, the Ministry of Health recognized community transmission throughout Brazilian territory. On May 15, Brazil held sixth place worldwide in total cases, with more than 200,000 individuals infected and more than 13,000 deaths.<sup><xref ref-type="bibr" rid="B3">3</xref></sup></p>
      <p>The most relevant aspects that should be observed during the course of the pandemic include the groups at greatest risk; in this group, individuals over the age of 60 and those with cardiovascular comorbidities stand out, as these factors are associated with worse prognosis and greater lethality when patients are infected with the novel coronavirus.<sup><xref ref-type="bibr" rid="B4">4</xref></sup></p>
      <p>The objective of this study was to analyze the association between the existence of previous circulatory system diseases and time (in days) from onset of first symptoms to date of death due to COVID-19.</p>
      <p>This is a case-control study, involving data from 374 deaths due to COVID-19, registered in the state of Pernambuco, Brazil. Data were obtained from the state&#8217;s COVID-19 monitoring webpage (https://dados.seplag.pe.gov.br/apps/corona.html), on May 7, 2020. After collection, the database underwent adjustment of variables, which consisted of evaluation of signs/symptoms and comorbidities. Following adaptation, 197 individuals had prior circulatory system disease, 187 of which included date of onset of symptoms and date of death. These individuals constituted the case group. To form the control group, 187 deaths without related comorbidities were selected. Selection of these deaths was random, following the date of onset of symptoms.</p>
      <p>In this study, the following variables were considered: existing comorbidities (none, one, two, and three or more) and time (in days) from onset of symptoms to death due to COVID-19. For statistical analysis, the Kolmogorov-Smirnov test was used for initial evaluation of data normality. When violation of the presupposed Gaussian distribution was found, association between variables was evaluated by nonparametric Mann-Whitney U test. Analyses considered a significance level of 5%, and they were carried out with the help of SPSS software, version 24.0 (IBM Corporation). Given that the study used public domain data, wherein it is not possible to identify the individuals, approval by the Research Ethics Committee was waived for this study.</p>
      <p>Average and standard deviation (average &#177; SD) and median and interquartile range (median &#8211; IQR) of days from onset of first symptoms to date of death for the whole study population (n = 374) were 11.52 (&#177; 7.75) and 10 (IIQ 10), respectively. In the case group, 38 (20.3%) had only one circulatory system disease; 79 (42.2%) had two comorbidities/risk factors, and 70 (37.5%) had three or more comorbidities/risk factors. It is worth highlighting that at least one of the comorbidities was related to the circulatory system ( <xref ref-type="fig" rid="f01001">Figure 1</xref> ).</p>
      <p>
        <fig id="f01001">
          <label>Figure 1</label>
          <caption>
            <title>&#8211; <italic>Comparison between number of days from onset of first symptoms to death due to COVID-19, according to presence or absence of comorbidities. Brazil, 2020.</italic></title>
          </caption>
          <graphic xlink:href="1678-4170-abc-115-01-0146-00486-gf01-en.tif"/></fig>
      </p>
      <p>A significant difference was observed regarding the number of days from onset of first symptoms to death when comparing the two groups. The values observed in the control group (average &#177; SD = 13.32 &#177; 7.2; median &#8211; IQR = 11 &#8211; 11) were higher than those in the group with reported comorbidities (average &#177; SD = 9.73 &#177; 7.8; median &#8211; IQR = 7 &#8211; 9) ( <xref ref-type="fig" rid="f01001">Figure 1</xref> ).</p>
      <p>This study indicates more rapid progression of COVID-19 in patients with cardiovascular comorbidities; average number of days from onset of first symptoms to death was lower by almost four days (3.9 days for average and 4.0 days for median), when comparing the group that had prior cardiovascular disease to the control group. This process results from the effects of SARS-CoV-2 in the human body, such as the binding of the virus to angiotensin-converting enzyme 2 (ACE2) found in the surface of heart, kidney, and lung cells.<sup><xref ref-type="bibr" rid="B4">4</xref></sup></p>
      <p>Exposure of glycoproteins related to the novel coronavirus to ACE2 promotes internalization together with the virus, which diminishes the density of ACE2 in the membrane<sup><xref ref-type="bibr" rid="B5">5</xref> , <xref ref-type="bibr" rid="B6">6</xref></sup> and, consequently, the cardioprotective effect related to cardiac hypertrophy, myocardial fibrosis, and inflammation. Accordingly, the reduction of ACE2 is associated with the exacerbation of existing heart diseases, such as heart failure and arterial hypertension, contributing to more rapid progression and worsening of respiratory and cardiovascular condition of individuals with COVID-19.</p>
      <p>Based on the observed results, the presence of cardiovascular comorbidities accelerates mortality due to COVID-19. Furthermore, future studies need to be performed with the aim of measuring the impact of each cardiovascular disease on risk of mortality.</p>
    </body>
  </sub-article>
</article>
