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<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" article-type="research-article" dtd-version="1.1" specific-use="sps-1.9" xml:lang="en">
  <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">hWVfNh9SZ5LNCZCxGJygCZs</article-id>
      <article-id specific-use="scielo-v2" pub-id-type="publisher-id">S0066-782X2020000200222</article-id>
      <article-id pub-id-type="doi">10.36660/abc.20180321</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Original Article</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>A 10-Year Trend Analysis of Heart Failure in the Less Developed Brazil</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-7443-5029</contrib-id>
          <name>
            <surname>Fernandes</surname>
            <given-names>Amanda D. F.</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">1</xref>
          <xref ref-type="corresp" rid="c1"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Fernandes</surname>
            <given-names>Gilson C.</given-names>
          </name>
          <xref ref-type="aff" rid="aff2">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Mazza</surname>
            <given-names>Manuel Rivera</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Knijnik</surname>
            <given-names>Leonardo M.</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Fernandes</surname>
            <given-names>Gustavo Soares</given-names>
          </name>
          <xref ref-type="aff" rid="aff3">3</xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-8656-870X</contrib-id>
          <name>
            <surname>Vilela</surname>
            <given-names>Andre Telis de</given-names>
          </name>
          <xref ref-type="aff" rid="aff4">4</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Badiye</surname>
            <given-names>Amit</given-names>
          </name>
          <xref ref-type="aff" rid="aff2">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Chaparro</surname>
            <given-names>Sandra V.</given-names>
          </name>
          <xref ref-type="aff" rid="aff2">2</xref>
        </contrib>
      </contrib-group>
      <aff id="aff1">
        <label>1</label>
        <institution content-type="orgname">University of Miami Miller</institution>
        <institution content-type="orgdiv1">School of Medicine</institution>
        <institution content-type="orgdiv2">Department of Medicine</institution>
        <addr-line>
          <city>Miami</city>
          <state>Florida</state>
        </addr-line>
        <country country="US">USA</country>
        <institution content-type="original">University of Miami Miller School of Medicine - Department of Medicine, Miami, Florida - USA</institution>
      </aff>
      <aff id="aff2">
        <label>2</label>
        <institution content-type="orgname">University of Miami Miller</institution>
        <institution content-type="orgdiv1">School of Medicine</institution>
        <institution content-type="orgdiv2">Division of Cardiology</institution>
        <addr-line>
          <city>Miami</city>
          <state>Florida</state>
        </addr-line>
        <country country="US">USA</country>
        <institution content-type="original">University of Miami Miller School of Medicine - Division of Cardiology, Miami, Florida - USA</institution>
      </aff>
      <aff id="aff3">
        <label>3</label>
        <institution content-type="orgname">Centro Universitario de Joao Pessoa</institution>
        <addr-line>
          <city>Jo&#227;o Pessoa</city>
          <state>PB</state>
        </addr-line>
        <country country="BR">Brazil</country>
        <institution content-type="original">Centro Universitario de Joao Pessoa, Jo&#227;o Pessoa, PB - Brazil</institution>
      </aff>
      <aff id="aff4">
        <label>4</label>
        <institution content-type="orgname">Universidade Federal da Paraiba</institution>
        <addr-line>
          <city>Jo&#227;o Pessoa</city>
          <state>PB</state>
        </addr-line>
        <country country="BR">Brazil</country>
        <institution content-type="original">Universidade Federal da Paraiba, Jo&#227;o Pessoa, PB - Brazil</institution>
      </aff>
      <author-notes>
        <corresp id="c1"><bold>Mailing Address: Amanda D. F. Fernandes</bold>, University of Miami Miller School of Medicine - Department of Medicine - 1600 N.W. 10th Avenue Miami Fl&#243;rida 33136 - Estados Unidos. E-mail: <email>amandadantasff@gmail.com</email></corresp>
        <fn fn-type="con">
          <p>
            <bold>Author contributions</bold>
          </p>
          <p>Conception and design of the research: Fernandes ADF; Acquisition of data: Fernandes ADF, Knijnik LM, Fernandes GS; Analysis and interpretation of the data: Fernandes ADF, Fernandes GC, Knijnik LM; Statistical analysis: Fernandes ADF, Fernandes GC, Mazza MR; Writing of the manuscript: Fernandes ADF, Fernandes GC, Mazza MR, Knijnik LM, Fernandes GS; Critical revision of the manuscript for intellectual content: Fernandes ADF, Fernandes GC, Mazza MR, Knijnik LM, Vilela AT, Badiye A, Chaparro SV.</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>
      <pub-date publication-format="electronic" date-type="pub">
        <day>20</day>
        <month>03</month>
        <year>2020</year>
      </pub-date>
      <pub-date publication-format="electronic" date-type="collection">
        <month>02</month>
        <year>2020</year>
      </pub-date>
      <volume>114</volume>
      <issue>2</issue>
      <fpage>222</fpage>
      <lpage>231</lpage>
      <history>
        <date date-type="received">
          <day>07</day>
          <month>11</month>
          <year>2018</year>
        </date>
        <date date-type="rev-recd">
          <day>08</day>
          <month>03</month>
          <year>2019</year>
        </date>
        <date date-type="accepted">
          <day>10</day>
          <month>04</month>
          <year>2019</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 License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited</license-p>
        </license>
      </permissions>
      <abstract>
        <title>Abstract</title>
        <sec>
          <title>Background:</title>
          <p>Data on heart failure (HF) epidemiology in less developed areas of Brazil are scarce.</p>
        </sec>
        <sec>
          <title>Objective:</title>
          <p>Our aim was to determine the HF morbidity and mortality in Paraiba and Brazil and its 10-year trends.</p>
        </sec>
        <sec>
          <title>Methods:</title>
          <p>A retrospective search was conducted from 2008 to 2017 using the DATASUS database and included patients &#8805; 15 years old with a primary diagnosis of HF. Data on in-hospital and population morbidity and mortality were collected and stratified by year, gender and age. Pearson correlation and linear-by-linear association test for trends were calculated, with a level of significance of 5%.</p>
        </sec>
        <sec>
          <title>Results:</title>
          <p>From 2008 to 2017, HF admissions decreased 62% (p = 0.004) in Paraiba and 34% (p = 0.004) in Brazil. The in-hospital mortality rate increased in Paraiba and Brazil [65.1% (p = 0.006) and 30.1% (p = 0.003), respectively], but the absolute in-hospital mortality had a significant decrease only in Paraiba [37.5% (p = 0.013)], which was maintained after age stratification, except for groups 15-19, 60-69 and &gt; 80 years. It was observed an increase in the hospital stay [44% (p = 0.004) in Paraiba and 12.3% (p = 0.004) in Brazil]. From 2008 to 2015, mortality rate for HF in the population decreased 10.7% (p = 0.047) in Paraiba and 7.7% (p = 0.017) in Brazil.</p>
        </sec>
        <sec>
          <title>Conclusions:</title>
          <p>Although HF mortality rate has been decreasing in Paraiba and Brazil, an increase in the in-hospital mortality rate and length of stay for HF has been observed. Hospital-based clinical studies should be performed to identify the causes for these trends of increase.</p>
        </sec>
      </abstract>
      <kwd-group xml:lang="en">
        <title>Keywords:</title>
        <kwd>Heart Failure/physiopathology</kwd>
        <kwd>Heart Failure/mortality</kwd>
        <kwd>Heart Failure/epidemiology</kwd>
        <kwd>Comorbidity</kwd>
        <kwd>Heart Failure/trends</kwd>
        <kwd>Hospitalization</kwd>
      </kwd-group>
    </article-meta>
  </front>
  <body>
    <sec sec-type="intro">
      <title>Introduction</title>
      <p>Heart Failure (HF) is the main cause of hospitalizations in the United States in patients older than 65 years old,<xref ref-type="bibr" rid="B1">1</xref><sup>,</sup><xref ref-type="bibr" rid="B2">2</xref> and is estimated to affect 26 million people worldwide.<xref ref-type="bibr" rid="B3">3</xref> Its prevalence has been increasing fast due to aging of the population.<xref ref-type="bibr" rid="B1">1</xref><sup>,</sup><xref ref-type="bibr" rid="B4">4</xref> A higher life expectancy has been achieved with adherence to medical therapy, ventricular assist devices (VADs) and increase in the number of heart transplants.<xref ref-type="bibr" rid="B1">1</xref></p>
      <p>Paraiba is one of the nine states of the Northeast region of Brazil and had an estimated population in 2017 of 4,025,558 inhabitants, corresponding to the 13<sup>th</sup> highest population among the 27 federative units of Brazil. The gross domestic product per capita of Paraiba was US$3,594.94 in 2010, corresponding to fourth poorest state in the country, and the human development index in 2014 was 0.701, the 6<sup>th</sup> lowest in the country.<xref ref-type="bibr" rid="B5">5</xref><sup>,</sup><xref ref-type="bibr" rid="B6">6</xref> Data regarding the epidemiology of HF in less developed countries are still limited and based mainly in cohorts of hospitalized patients or clinical trials.<xref ref-type="bibr" rid="B2">2</xref> In Brazil, there is no data about the epidemiology of HF in Paraiba, and only a few reports on HF statistics in the Northeast region of Brazil.<xref ref-type="bibr" rid="B7">7</xref><sup>,</sup> <xref ref-type="bibr" rid="B8">8</xref></p>
      <p>A better understanding of the HF epidemiology in less developed areas of Brazil, as Paraiba, through a population-based study, could lead to a more effective and appropriate healthcare planning. The aim of this study was to describe and to perform a 10-year trend analysis of the HF morbidity and mortality in the state of Paraiba and in Brazil.</p>
    </sec>
    <sec sec-type="methods">
      <title>Methods</title>
      <sec>
        <title>Study model</title>
        <p>This is a population-based time series analysis using the Hospital Information System (SIH/SUS), available at DATASUS (Department of Informatics of the Brazilian Unified Health System- SUS) database.<xref ref-type="bibr" rid="B6">6</xref> DATASUS is responsible for the administration of health and financial information declared by all states and cities, and the federal district of Brazil. This database compiles information regarding health assistance, epidemiology, morbidity and demography.</p>
      </sec>
      <sec>
        <title>Study population</title>
        <p>The population of interest was composed by Brazilians older than 15 years that used any healthcare services under the primary diagnosis of HF, represented by the code I50 of the International Classification of Diseases 10<sup>th</sup> Revision (ICD-10), between 2008 and 2017.</p>
      </sec>
      <sec>
        <title>Variables</title>
        <p>Epidemiological data on HF were extracted, including absolute and relative mortality of the population, in-hospital mortality (absolute numbers), in-hospital mortality rate, number of hospital admissions and length of hospitalization. Variables were stratified by year, gender and age groups (15-19, 20-29, 30-39, 40-49, 50-59, 60-69, 70-79 and &#8805; 80 years). In-hospital data from the period of 2008 to 2017, and population data from 2008 to 2015 were available. The last population census conducted by the Brazilian Institute of Geography and Statistics (IBGE)<xref ref-type="bibr" rid="B5">5</xref> in 2010 was also used.</p>
      </sec>
      <sec>
        <title>Data analysis</title>
        <p>Categorical variables were expressed as frequencies and continuous variables as mean &#177; standard deviation (SD).</p>
        <p>In-hospital mortality rate from HF was obtained by dividing the number of all in-hospital HF deaths in Paraiba or Brazil by the number of hospitalizations for HF in the corresponding year. Population mortality rate from HF was calculated by dividing the number of all HF deaths in Paraiba or Brazil by the respective population in the corresponding year.</p>
        <p>The Statistical Package for the Social Sciences (SPSS) version 21.0 (SPPS Inc., Chicago, USA) was used for the analysis. We used the Shapiro-Wilk&#8217;s test to test the normality of data distribution for further analyses. The Pearson correlation was used to evaluate the correlation between numerical variables with normal distribution. The Chi-square test was performed using a contingency table and the linear-by-linear association test, also known as Mantel-Haenzsel test for trends, which is equivalent to the Cochran-Armitage test for trends available in other statistical packages.<xref ref-type="bibr" rid="B9">9</xref> The level of significance was set at 5%.</p>
      </sec>
    </sec>
    <sec sec-type="results">
      <title>Results</title>
      <p>Descriptive statistics of our variables are presented in <xref ref-type="table" rid="t1">Table 1</xref>.</p>
      <table-wrap id="t1">
        <label>Table 1</label>
        <caption>
          <title>Descriptive statistics of Heart Failure epidemiology in Paraiba, from 2008 to 2017</title>
        </caption>
        <table frame="hsides" rules="groups">
          <colgroup>
            <col width="25%"/>
            <col width="25%"/>
            <col width="25%"/>
            <col width="25%"/>
          </colgroup>
          <thead>
            <tr>
              <th align="left">Variables</th>
              <th align="center">Mean</th>
              <th align="center">Standard deviation</th>
              <th align="center">Shapiro-Wilk significance<xref ref-type="table-fn" rid="TFN1">*</xref></th>
            </tr>
          </thead>
          <tbody>
            <tr>
              <td align="left">Deaths (population)<sup><xref ref-type="table-fn" rid="TFN2">&#8224;</xref></sup></td>
              <td align="center">739.88</td>
              <td align="center">32.92</td>
              <td align="center">0.385</td>
            </tr>
            <tr>
              <td align="left">Women</td>
              <td align="center">387.88</td>
              <td align="center">24.07</td>
              <td align="center">0.916</td>
            </tr>
            <tr>
              <td align="left">Men</td>
              <td align="center">349.63</td>
              <td align="center">17.71</td>
              <td align="center">0.099</td>
            </tr>
            <tr>
              <td align="left">Deaths (in-hospital)</td>
              <td align="center">474.50</td>
              <td align="center">95.52</td>
              <td align="center">0.324</td>
            </tr>
            <tr>
              <td align="left">Women</td>
              <td align="center">238.80</td>
              <td align="center">46.15</td>
              <td align="center">0.763</td>
            </tr>
            <tr>
              <td align="left">Men</td>
              <td align="center">234.70</td>
              <td align="center">52.04</td>
              <td align="center">0.161</td>
            </tr>
            <tr>
              <td align="left">Population mortality rate (per 100,000) <sup><xref ref-type="table-fn" rid="TFN2">&#8224;</xref></sup></td>
              <td align="center">19.16</td>
              <td align="center">1.09</td>
              <td align="center">0.775</td>
            </tr>
            <tr>
              <td align="left">In-hospital mortality rate (per 100)</td>
              <td align="center">9.76</td>
              <td align="center">1.84</td>
              <td align="center">0.659</td>
            </tr>
            <tr>
              <td align="left">Number of admissions</td>
              <td align="center">5117.20</td>
              <td align="center">1805.13</td>
              <td align="center">0.176</td>
            </tr>
            <tr>
              <td align="left">Mean duration of hospitalization (days)</td>
              <td align="center">5.92</td>
              <td align="center">0.80</td>
              <td align="center">0.121</td>
            </tr>
          </tbody>
        </table>
        <table-wrap-foot>
          <fn id="TFN1">
            <label>*</label>
            <p>In the Shapiro-Wilk test, the null hypothesis is that the population follows a normal distribution; if p &lt; 0.05, the data is not normally distributed;</p>
          </fn>
          <fn id="TFN2">
            <label>&#8224;</label>
            <p>Year interval: 2008-2015;</p>
          </fn>
          <attrib>Source of data: SUS Information System (DATASUS) and Brazilian Institute of Geography and Statistics (2010).</attrib>
        </table-wrap-foot>
      </table-wrap>
      <sec>
        <title>Hospitalizations</title>
        <p>The total number of HF admissions in Paraiba state between 2008 and 2017 was 51,172, representing the leading cause of hospitalizations due to cardiovascular diseases (29.4%), followed by other ischemic diseases of the heart (13%), stroke (11%), primary hypertension (10%) and acute myocardial infarction (5%). During the same period, HF was also the leading cardiovascular cause of hospitalization in Brazil, with 2,380,133 cases (21%). HF was responsible for 2.54% and 2.25% of all causes of hospitalization in Paraiba and in Brazil, respectively.</p>
        <p>A downward trend in the absolute number of hospitalizations from HF in Paraiba and Brazil was observed between 2008 and 2017, corresponding to a decrease of 62% (R = -0.970; p = 0.004; <xref ref-type="table" rid="t2">Table 2</xref>; <xref ref-type="fig" rid="f1">Figure 1A</xref>) and 34% (R = -0.964; p = 0.004; <xref ref-type="table" rid="t3">Table 3</xref>; <xref ref-type="fig" rid="f1">Figure 1B</xref>), respectively. The frequency of males hospitalized for HF was 52% in Paraiba and 51% in Brazil.</p>
        <table-wrap id="t2">
          <label>Table 2</label>
          <caption>
            <title>Heart failure trends in Paraiba, from 2008 to 2017</title>
          </caption>
          <table frame="hsides" rules="groups">
            <colgroup>
              <col width="7%"/>
              <col width="7%"/>
              <col width="7%"/>
              <col width="7%"/>
              <col width="7%"/>
              <col width="7%"/>
              <col width="7%"/>
              <col width="7%"/>
              <col width="7%"/>
              <col width="7%"/>
              <col width="7%"/>
              <col width="7%"/>
              <col width="7%"/>
            </colgroup>
            <thead>
              <tr>
                <th align="left">Variables</th>
                <th align="center">2008</th>
                <th align="center">2009</th>
                <th align="center">2010</th>
                <th align="center">2011</th>
                <th align="center">2012</th>
                <th align="center">2013</th>
                <th align="center">2014</th>
                <th align="center">2015</th>
                <th align="center">2016</th>
                <th align="center">2017</th>
                <th align="center">P values for trends<xref ref-type="table-fn" rid="TFN3">*</xref><sup><xref ref-type="table-fn" rid="TFN4">&#8224;</xref></sup></th>
                <th align="center">Pearson (R)</th>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td align="left">Number of deaths (population)</td>
                <td align="center">722</td>
                <td align="center">777</td>
                <td align="center">772</td>
                <td align="center">753</td>
                <td align="center">719</td>
                <td align="center">768</td>
                <td align="center">725</td>
                <td align="center">683</td>
                <td align="center">------</td>
                <td align="center">------</td>
                <td align="center">0.175</td>
                <td align="center">-0.513</td>
              </tr>
              <tr>
                <td align="left">Women</td>
                <td align="center">365</td>
                <td align="center">398</td>
                <td align="center">390</td>
                <td align="center">413</td>
                <td align="center">386</td>
                <td align="center">421</td>
                <td align="center">383</td>
                <td align="center">347</td>
                <td align="center">------</td>
                <td align="center">------</td>
                <td align="center">0.665</td>
                <td align="center">-0.164</td>
              </tr>
              <tr>
                <td align="left">Men</td>
                <td align="center">351</td>
                <td align="center">374</td>
                <td align="center">379</td>
                <td align="center">337</td>
                <td align="center">332</td>
                <td align="center">347</td>
                <td align="center">341</td>
                <td align="center">336</td>
                <td align="center">------</td>
                <td align="center">------</td>
                <td align="center">0.130</td>
                <td align="center">-0.573</td>
              </tr>
              <tr>
                <td align="left">Number of deaths (in-hospital)</td>
                <td align="center">472</td>
                <td align="center">588</td>
                <td align="center">581</td>
                <td align="center">561</td>
                <td align="center">551</td>
                <td align="center">462</td>
                <td align="center">461</td>
                <td align="center">374</td>
                <td align="center">378</td>
                <td align="center">317</td>
                <td align="center">0.013<xref ref-type="table-fn" rid="TFN3">*</xref></td>
                <td align="center">-0.824</td>
              </tr>
              <tr>
                <td align="left">Women</td>
                <td align="center">220</td>
                <td align="center">310</td>
                <td align="center">294</td>
                <td align="center">282</td>
                <td align="center">265</td>
                <td align="center">235</td>
                <td align="center">224</td>
                <td align="center">207</td>
                <td align="center">188</td>
                <td align="center">173</td>
                <td align="center">0.022<xref ref-type="table-fn" rid="TFN3">*</xref></td>
                <td align="center">-0.762</td>
              </tr>
              <tr>
                <td align="left">Men</td>
                <td align="center">252</td>
                <td align="center">278</td>
                <td align="center">287</td>
                <td align="center">279</td>
                <td align="center">286</td>
                <td align="center">227</td>
                <td align="center">237</td>
                <td align="center">167</td>
                <td align="center">190</td>
                <td align="center">144</td>
                <td align="center">0.012<xref ref-type="table-fn" rid="TFN3">*</xref></td>
                <td align="center">-0.837</td>
              </tr>
              <tr>
                <td align="left">Mortality rate (population)</td>
                <td align="center">19,25</td>
                <td align="center">20.53</td>
                <td align="center">20.21</td>
                <td align="center">19.55</td>
                <td align="center">18.51</td>
                <td align="center">19.62</td>
                <td align="center">18.38</td>
                <td align="center">17.19</td>
                <td align="center">------</td>
                <td align="center">------</td>
                <td align="center">0.047<xref ref-type="table-fn" rid="TFN3">*</xref></td>
                <td align="center">-0.751</td>
              </tr>
              <tr>
                <td align="left">Mortality rate (in-hospital)</td>
                <td align="center">6.60</td>
                <td align="center">8.50</td>
                <td align="center">7.90</td>
                <td align="center">8.50</td>
                <td align="center">10.10</td>
                <td align="center">9.8</td>
                <td align="center">11.20</td>
                <td align="center">12.00</td>
                <td align="center">12.10</td>
                <td align="center">10.90</td>
                <td align="center">0.006<xref ref-type="table-fn" rid="TFN3">*</xref></td>
                <td align="center">0.917</td>
              </tr>
              <tr>
                <td align="left">Women</td>
                <td align="center">6.35</td>
                <td align="center">9.32</td>
                <td align="center">8.52</td>
                <td align="center">9.02</td>
                <td align="center">10.08</td>
                <td align="center">10.39</td>
                <td align="center">11.49</td>
                <td align="center">13.56</td>
                <td align="center">12.69</td>
                <td align="center">11.93</td>
                <td align="center">0.006<xref ref-type="table-fn" rid="TFN3">*</xref></td>
                <td align="center">0.908</td>
              </tr>
              <tr>
                <td align="left">Men</td>
                <td align="center">6.76</td>
                <td align="center">7.67</td>
                <td align="center">7.36</td>
                <td align="center">8.15</td>
                <td align="center">10.20</td>
                <td align="center">9.12</td>
                <td align="center">11.02</td>
                <td align="center">10.61</td>
                <td align="center">11.59</td>
                <td align="center">9.40</td>
                <td align="center">0.013<xref ref-type="table-fn" rid="TFN3">*</xref></td>
                <td align="center">0.828</td>
              </tr>
              <tr>
                <td align="left">Number of admissions</td>
                <td align="center">7143</td>
                <td align="center">6890</td>
                <td align="center">7331</td>
                <td align="center">6571</td>
                <td align="center">5450</td>
                <td align="center">4739</td>
                <td align="center">4102</td>
                <td align="center">3112</td>
                <td align="center">3115</td>
                <td align="center">2719</td>
                <td align="center">0.004<xref ref-type="table-fn" rid="TFN3">*</xref></td>
                <td align="center">-0.970</td>
              </tr>
              <tr>
                <td align="left">
                  <bold>Deaths per age range (population)</bold>
                </td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
              </tr>
              <tr>
                <td align="left">15-19 years</td>
                <td align="center">2</td>
                <td align="center">2</td>
                <td align="center">3</td>
                <td align="center">2</td>
                <td align="center">1</td>
                <td align="center">0</td>
                <td align="center">1</td>
                <td align="center">1</td>
                <td align="center">------</td>
                <td align="center">------</td>
                <td align="center">0.067</td>
                <td align="center">-0.693</td>
              </tr>
              <tr>
                <td align="left">20-29 years</td>
                <td align="center">3</td>
                <td align="center">8</td>
                <td align="center">8</td>
                <td align="center">5</td>
                <td align="center">5</td>
                <td align="center">6</td>
                <td align="center">2</td>
                <td align="center">6</td>
                <td align="center">------</td>
                <td align="center">------</td>
                <td align="center">0.588</td>
                <td align="center">-0.205</td>
              </tr>
              <tr>
                <td align="left">30-39 years</td>
                <td align="center">8</td>
                <td align="center">16</td>
                <td align="center">9</td>
                <td align="center">13</td>
                <td align="center">9</td>
                <td align="center">10</td>
                <td align="center">10</td>
                <td align="center">8</td>
                <td align="center">------</td>
                <td align="center">------</td>
                <td align="center">0.389</td>
                <td align="center">-0.326</td>
              </tr>
              <tr>
                <td align="left">40-49 years</td>
                <td align="center">21</td>
                <td align="center">22</td>
                <td align="center">29</td>
                <td align="center">23</td>
                <td align="center">25</td>
                <td align="center">23</td>
                <td align="center">24</td>
                <td align="center">13</td>
                <td align="center">------</td>
                <td align="center">------</td>
                <td align="center">0.292</td>
                <td align="center">-0.399</td>
              </tr>
              <tr>
                <td align="left">50-59 years</td>
                <td align="center">47</td>
                <td align="center">42</td>
                <td align="center">53</td>
                <td align="center">33</td>
                <td align="center">45</td>
                <td align="center">48</td>
                <td align="center">46</td>
                <td align="center">36</td>
                <td align="center">------</td>
                <td align="center">------</td>
                <td align="center">0.479</td>
                <td align="center">-0.267</td>
              </tr>
              <tr>
                <td align="left">60-69 years</td>
                <td align="center">84</td>
                <td align="center">88</td>
                <td align="center">92</td>
                <td align="center">75</td>
                <td align="center">92</td>
                <td align="center">101</td>
                <td align="center">82</td>
                <td align="center">93</td>
                <td align="center">------</td>
                <td align="center">------</td>
                <td align="center">0.457</td>
                <td align="center">0.281</td>
              </tr>
              <tr>
                <td align="left">70-79 years</td>
                <td align="center">164</td>
                <td align="center">172</td>
                <td align="center">152</td>
                <td align="center">172</td>
                <td align="center">147</td>
                <td align="center">179</td>
                <td align="center">174</td>
                <td align="center">154</td>
                <td align="center">------</td>
                <td align="center">------</td>
                <td align="center">0.979</td>
                <td align="center">-0.010</td>
              </tr>
              <tr>
                <td align="left">Older than 80 years</td>
                <td align="center">387</td>
                <td align="center">422</td>
                <td align="center">423</td>
                <td align="center">427</td>
                <td align="center">394</td>
                <td align="center">401</td>
                <td align="center">385</td>
                <td align="center">372</td>
                <td align="center">------</td>
                <td align="center">------</td>
                <td align="center">0.143</td>
                <td align="center">-0.553</td>
              </tr>
              <tr>
                <td align="left">
                  <bold>Deaths per age range (in-hospital)</bold>
                </td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
              </tr>
              <tr>
                <td align="left">15-19 years</td>
                <td align="center">3</td>
                <td align="center">2</td>
                <td align="center">3</td>
                <td align="center">3</td>
                <td align="center">2</td>
                <td align="center">2</td>
                <td align="center">2</td>
                <td align="center">2</td>
                <td align="center">4</td>
                <td align="center">2</td>
                <td align="center">0.815</td>
                <td align="center">-0.078</td>
              </tr>
              <tr>
                <td align="left">20-29 years</td>
                <td align="center">11</td>
                <td align="center">10</td>
                <td align="center">8</td>
                <td align="center">5</td>
                <td align="center">5</td>
                <td align="center">4</td>
                <td align="center">4</td>
                <td align="center">7</td>
                <td align="center">2</td>
                <td align="center">2</td>
                <td align="center">0.010<xref ref-type="table-fn" rid="TFN3">*</xref></td>
                <td align="center">-0.859</td>
              </tr>
              <tr>
                <td align="left">30-39 years</td>
                <td align="center">17</td>
                <td align="center">19</td>
                <td align="center">16</td>
                <td align="center">11</td>
                <td align="center">16</td>
                <td align="center">12</td>
                <td align="center">7</td>
                <td align="center">8</td>
                <td align="center">6</td>
                <td align="center">8</td>
                <td align="center">0.008<xref ref-type="table-fn" rid="TFN3">*</xref></td>
                <td align="center">-0.887</td>
              </tr>
              <tr>
                <td align="left">40-49 years</td>
                <td align="center">24</td>
                <td align="center">35</td>
                <td align="center">35</td>
                <td align="center">35</td>
                <td align="center">36</td>
                <td align="center">30</td>
                <td align="center">19</td>
                <td align="center">10</td>
                <td align="center">10</td>
                <td align="center">17</td>
                <td align="center">0.029<xref ref-type="table-fn" rid="TFN3">*</xref></td>
                <td align="center">-0.727</td>
              </tr>
              <tr>
                <td align="left">50-59 years</td>
                <td align="center">55</td>
                <td align="center">53</td>
                <td align="center">53</td>
                <td align="center">55</td>
                <td align="center">63</td>
                <td align="center">47</td>
                <td align="center">46</td>
                <td align="center">24</td>
                <td align="center">38</td>
                <td align="center">35</td>
                <td align="center">0.025<xref ref-type="table-fn" rid="TFN3">*</xref></td>
                <td align="center">-0.748</td>
              </tr>
              <tr>
                <td align="left">60-69 years</td>
                <td align="center">77</td>
                <td align="center">97</td>
                <td align="center">96</td>
                <td align="center">97</td>
                <td align="center">101</td>
                <td align="center">86</td>
                <td align="center">93</td>
                <td align="center">72</td>
                <td align="center">76</td>
                <td align="center">44</td>
                <td align="center">0.061</td>
                <td align="center">-0.625</td>
              </tr>
              <tr>
                <td align="left">70-79 years</td>
                <td align="center">129</td>
                <td align="center">150</td>
                <td align="center">136</td>
                <td align="center">142</td>
                <td align="center">131</td>
                <td align="center">119</td>
                <td align="center">129</td>
                <td align="center">96</td>
                <td align="center">89</td>
                <td align="center">75</td>
                <td align="center">0.009<xref ref-type="table-fn" rid="TFN3">*</xref></td>
                <td align="center">-0.865</td>
              </tr>
              <tr>
                <td align="left">Older than 80 years</td>
                <td align="center">149</td>
                <td align="center">213</td>
                <td align="center">227</td>
                <td align="center">211</td>
                <td align="center">194</td>
                <td align="center">157</td>
                <td align="center">156</td>
                <td align="center">153</td>
                <td align="center">148</td>
                <td align="center">129</td>
                <td align="center">0.052</td>
                <td align="center">-0.649</td>
              </tr>
              <tr>
                <td align="left">Mean duration of hospitalization (days)</td>
                <td align="center">5</td>
                <td align="center">5.2</td>
                <td align="center">5.3</td>
                <td align="center">5.5</td>
                <td align="center">5.6</td>
                <td align="center">5.6</td>
                <td align="center">6.1</td>
                <td align="center">6.5</td>
                <td align="center">7.2</td>
                <td align="center">7.2</td>
                <td align="center">0.004<xref ref-type="table-fn" rid="TFN3">*</xref></td>
                <td align="center">0.953</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN3">
              <label>*</label>
              <p>p &lt; 0.05;</p>
            </fn>
            <fn id="TFN4">
              <label>&#8224;</label>
              <p>P value for trends according to the linear-by-linear association;</p>
            </fn>
            <attrib>Source of data: SUS Information System (DATASUS) and Brazilian Institute of Geography and Statistics (count of 2010).</attrib>
          </table-wrap-foot>
        </table-wrap>
        <table-wrap id="t3">
          <label>Table 3</label>
          <caption>
            <title>Heart failure trends in Brazil, from 2008 to 2017</title>
          </caption>
          <table frame="hsides" rules="groups">
            <colgroup>
              <col width="7%"/>
              <col width="7%"/>
              <col width="7%"/>
              <col width="7%"/>
              <col width="7%"/>
              <col width="7%"/>
              <col width="7%"/>
              <col width="7%"/>
              <col width="7%"/>
              <col width="7%"/>
              <col width="7%"/>
              <col width="7%"/>
              <col width="7%"/>
            </colgroup>
            <thead>
              <tr>
                <th align="left">Variables</th>
                <th align="center">2008</th>
                <th align="center">2009</th>
                <th align="center">2010</th>
                <th align="center">2011</th>
                <th align="center">2012</th>
                <th align="center">2013</th>
                <th align="center">2014</th>
                <th align="center">2015</th>
                <th align="center">2016</th>
                <th align="center">2017</th>
                <th align="center">P values for trends<xref ref-type="table-fn" rid="TFN5">*</xref><sup><xref ref-type="table-fn" rid="TFN6">&#8224;</xref></sup></th>
                <th align="center">Pearson (R)</th>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td align="left">Number of deaths (population)</td>
                <td align="center">27,567</td>
                <td align="center">27,314</td>
                <td align="center">27,544</td>
                <td align="center">27,818</td>
                <td align="center">26,694</td>
                <td align="center">27,290</td>
                <td align="center">26,783</td>
                <td align="center">27,434</td>
                <td align="center">------</td>
                <td align="center">------</td>
                <td align="center">0.276</td>
                <td align="center">-0.412</td>
              </tr>
              <tr>
                <td align="left">Women</td>
                <td align="center">13,990</td>
                <td align="center">14,136</td>
                <td align="center">14,236</td>
                <td align="center">14,525</td>
                <td align="center">13,824</td>
                <td align="center">14,014</td>
                <td align="center">13,846</td>
                <td align="center">14,435</td>
                <td align="center">------</td>
                <td align="center">------</td>
                <td align="center">0.929</td>
                <td align="center">0.034</td>
              </tr>
              <tr>
                <td align="left">Men</td>
                <td align="center">13,428</td>
                <td align="center">13,047</td>
                <td align="center">13,159</td>
                <td align="center">13,130</td>
                <td align="center">12,756</td>
                <td align="center">13,166</td>
                <td align="center">12,825</td>
                <td align="center">12,900</td>
                <td align="center">------</td>
                <td align="center">------</td>
                <td align="center">0.069</td>
                <td align="center">-0.689</td>
              </tr>
              <tr>
                <td align="left">Number of deaths (in-hospital)</td>
                <td align="center">22,513</td>
                <td align="center">23,043</td>
                <td align="center">23,667</td>
                <td align="center">24,451</td>
                <td align="center">23,071</td>
                <td align="center">22,858</td>
                <td align="center">22,031</td>
                <td align="center">22,756</td>
                <td align="center">23,519</td>
                <td align="center">19,209</td>
                <td align="center">0.131</td>
                <td align="center">-0.504</td>
              </tr>
              <tr>
                <td align="left">Women</td>
                <td align="center">11,021</td>
                <td align="center">11,356</td>
                <td align="center">11,740</td>
                <td align="center">12,099</td>
                <td align="center">11,426</td>
                <td align="center">11,305</td>
                <td align="center">10,963</td>
                <td align="center">11,450</td>
                <td align="center">11,738</td>
                <td align="center">10,509</td>
                <td align="center">0.401</td>
                <td align="center">-0.280</td>
              </tr>
              <tr>
                <td align="left">Men</td>
                <td align="center">11,198</td>
                <td align="center">11,395</td>
                <td align="center">11,676</td>
                <td align="center">12,092</td>
                <td align="center">11,408</td>
                <td align="center">11,301</td>
                <td align="center">10,823</td>
                <td align="center">11,097</td>
                <td align="center">11,577</td>
                <td align="center">10,213</td>
                <td align="center">0.119</td>
                <td align="center">-0.520</td>
              </tr>
              <tr>
                <td align="left">Mortality rate (population)</td>
                <td align="center">14.54</td>
                <td align="center">14.26</td>
                <td align="center">14.44</td>
                <td align="center">14.46</td>
                <td align="center">13.76</td>
                <td align="center">13.57</td>
                <td align="center">13.21</td>
                <td align="center">13.42</td>
                <td align="center">------</td>
                <td align="center">------</td>
                <td align="center">0.017<xref ref-type="table-fn" rid="TFN5">*</xref></td>
                <td align="center">-0.905</td>
              </tr>
              <tr>
                <td align="left">Mortality rate (in-hospital)</td>
                <td align="center">8.3</td>
                <td align="center">8.5</td>
                <td align="center">8.9</td>
                <td align="center">9.4</td>
                <td align="center">9.5</td>
                <td align="center">9.7</td>
                <td align="center">9.8</td>
                <td align="center">10.5</td>
                <td align="center">11.0</td>
                <td align="center">10.8</td>
                <td align="center">0.003<xref ref-type="table-fn" rid="TFN5">*</xref></td>
                <td align="center">0.981</td>
              </tr>
              <tr>
                <td align="left">Women</td>
                <td align="center">8.5</td>
                <td align="center">8.7</td>
                <td align="center">9.2</td>
                <td align="center">9.6</td>
                <td align="center">9.8</td>
                <td align="center">10.0</td>
                <td align="center">10.2</td>
                <td align="center">11.0</td>
                <td align="center">11.5</td>
                <td align="center">11.2</td>
                <td align="center">0.003<xref ref-type="table-fn" rid="TFN5">*</xref></td>
                <td align="center">0.980</td>
              </tr>
              <tr>
                <td align="left">Men</td>
                <td align="center">8.2</td>
                <td align="center">8.4</td>
                <td align="center">8.7</td>
                <td align="center">9.2</td>
                <td align="center">9.3</td>
                <td align="center">9.4</td>
                <td align="center">9.6</td>
                <td align="center">10.1</td>
                <td align="center">10.6</td>
                <td align="center">10.4</td>
                <td align="center">0.003<xref ref-type="table-fn" rid="TFN5">*</xref></td>
                <td align="center">0.985</td>
              </tr>
              <tr>
                <td align="left">Number of admissions</td>
                <td align="center">270,988</td>
                <td align="center">269,891</td>
                <td align="center">265,038</td>
                <td align="center">260,995</td>
                <td align="center">242,919</td>
                <td align="center">236,550</td>
                <td align="center">223,825</td>
                <td align="center">217,050</td>
                <td align="center">214,432</td>
                <td align="center">178,445</td>
                <td align="center">0.004<xref ref-type="table-fn" rid="TFN5">*</xref></td>
                <td align="center">-0.964</td>
              </tr>
              <tr>
                <td align="left">
                  <bold>Deaths per age range (population)</bold>
                </td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
              </tr>
              <tr>
                <td align="left">15-19 years</td>
                <td align="center">56</td>
                <td align="center">55</td>
                <td align="center">47</td>
                <td align="center">49</td>
                <td align="center">51</td>
                <td align="center">41</td>
                <td align="center">40</td>
                <td align="center">35</td>
                <td align="center">------</td>
                <td align="center">------</td>
                <td align="center">0.014<xref ref-type="table-fn" rid="TFN5">*</xref></td>
                <td align="center">-0.926</td>
              </tr>
              <tr>
                <td align="left">20-29 years</td>
                <td align="center">206</td>
                <td align="center">204</td>
                <td align="center">180</td>
                <td align="center">176</td>
                <td align="center">165</td>
                <td align="center">174</td>
                <td align="center">159</td>
                <td align="center">145</td>
                <td align="center">------</td>
                <td align="center">------</td>
                <td align="center">0.012<xref ref-type="table-fn" rid="TFN5">*</xref></td>
                <td align="center">-0.947</td>
              </tr>
              <tr>
                <td align="left">30-39 years</td>
                <td align="center">468</td>
                <td align="center">415</td>
                <td align="center">379</td>
                <td align="center">387</td>
                <td align="center">396</td>
                <td align="center">373</td>
                <td align="center">358</td>
                <td align="center">355</td>
                <td align="center">------</td>
                <td align="center">------</td>
                <td align="center">0.022<xref ref-type="table-fn" rid="TFN5">*</xref></td>
                <td align="center">-0.863</td>
              </tr>
              <tr>
                <td align="left">40-49 years</td>
                <td align="center">1,039</td>
                <td align="center">1,002</td>
                <td align="center">1,034</td>
                <td align="center">957</td>
                <td align="center">913</td>
                <td align="center">920</td>
                <td align="center">836</td>
                <td align="center">815</td>
                <td align="center">------</td>
                <td align="center">------</td>
                <td align="center">0.011<xref ref-type="table-fn" rid="TFN5">*</xref></td>
                <td align="center">-0.957</td>
              </tr>
              <tr>
                <td align="left">50-59 years</td>
                <td align="center">2,389</td>
                <td align="center">2,303</td>
                <td align="center">2,293</td>
                <td align="center">2,269</td>
                <td align="center">2,259</td>
                <td align="center">2,214</td>
                <td align="center">2,072</td>
                <td align="center">2,157</td>
                <td align="center">------</td>
                <td align="center">------</td>
                <td align="center">0.016<xref ref-type="table-fn" rid="TFN5">*</xref></td>
                <td align="center">-0.910</td>
              </tr>
              <tr>
                <td align="left">60-69 years</td>
                <td align="center">4,296</td>
                <td align="center">4,249</td>
                <td align="center">4,196</td>
                <td align="center">4,268</td>
                <td align="center">4,057</td>
                <td align="center">4,230</td>
                <td align="center">4,123</td>
                <td align="center">4,255</td>
                <td align="center">------</td>
                <td align="center">------</td>
                <td align="center">0.328</td>
                <td align="center">-0.370</td>
              </tr>
              <tr>
                <td align="left">70-79 years</td>
                <td align="center">7,178</td>
                <td align="center">7,027</td>
                <td align="center">7,062</td>
                <td align="center">7,013</td>
                <td align="center">6,727</td>
                <td align="center">6,969</td>
                <td align="center">6,707</td>
                <td align="center">6,845</td>
                <td align="center">------</td>
                <td align="center">------</td>
                <td align="center">0.037<xref ref-type="table-fn" rid="TFN5">*</xref></td>
                <td align="center">-0.788</td>
              </tr>
              <tr>
                <td align="left">Older than 80 years</td>
                <td align="center">11,788</td>
                <td align="center">11,928</td>
                <td align="center">12,206</td>
                <td align="center">12,539</td>
                <td align="center">12,012</td>
                <td align="center">12,259</td>
                <td align="center">12,383</td>
                <td align="center">12,733</td>
                <td align="center">------</td>
                <td align="center">------</td>
                <td align="center">0.039<xref ref-type="table-fn" rid="TFN5">*</xref></td>
                <td align="center">0.782</td>
              </tr>
              <tr>
                <td align="left">
                  <bold>Deaths per age range (in-hospital)</bold>
                </td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
                <td align="center">&#160;</td>
              </tr>
              <tr>
                <td align="left">15-19 years</td>
                <td align="center">87</td>
                <td align="center">97</td>
                <td align="center">75</td>
                <td align="center">73</td>
                <td align="center">61</td>
                <td align="center">65</td>
                <td align="center">59</td>
                <td align="center">61</td>
                <td align="center">61</td>
                <td align="center">38</td>
                <td align="center">0.007<xref ref-type="table-fn" rid="TFN5">*</xref></td>
                <td align="center">-0.898</td>
              </tr>
              <tr>
                <td align="left">20-29 years</td>
                <td align="center">284</td>
                <td align="center">271</td>
                <td align="center">264</td>
                <td align="center">241</td>
                <td align="center">220</td>
                <td align="center">230</td>
                <td align="center">188</td>
                <td align="center">176</td>
                <td align="center">175</td>
                <td align="center">152</td>
                <td align="center">0.003<xref ref-type="table-fn" rid="TFN5">*</xref></td>
                <td align="center">-0.984</td>
              </tr>
              <tr>
                <td align="left">30-39 years</td>
                <td align="center">597</td>
                <td align="center">529</td>
                <td align="center">503</td>
                <td align="center">501</td>
                <td align="center">475</td>
                <td align="center">451</td>
                <td align="center">445</td>
                <td align="center">437</td>
                <td align="center">434</td>
                <td align="center">369</td>
                <td align="center">0.008<xref ref-type="table-fn" rid="TFN5">*</xref></td>
                <td align="center">-0.887</td>
              </tr>
              <tr>
                <td align="left">40-49 years</td>
                <td align="center">1,278</td>
                <td align="center">1,216</td>
                <td align="center">1,227</td>
                <td align="center">1,216</td>
                <td align="center">1,104</td>
                <td align="center">1,102</td>
                <td align="center">981</td>
                <td align="center">1,004</td>
                <td align="center">1,052</td>
                <td align="center">853</td>
                <td align="center">0.005<xref ref-type="table-fn" rid="TFN5">*</xref></td>
                <td align="center">-0.931</td>
              </tr>
              <tr>
                <td align="left">50-59 years</td>
                <td align="center">2,687</td>
                <td align="center">2,722</td>
                <td align="center">2,736</td>
                <td align="center">2,793</td>
                <td align="center">2,700</td>
                <td align="center">2,620</td>
                <td align="center">2,372</td>
                <td align="center">2,498</td>
                <td align="center">2,569</td>
                <td align="center">2,149</td>
                <td align="center">0.019<xref ref-type="table-fn" rid="TFN5">*</xref></td>
                <td align="center">-0.783</td>
              </tr>
              <tr>
                <td align="left">60-69 years</td>
                <td align="center">4,358</td>
                <td align="center">4,578</td>
                <td align="center">4,739</td>
                <td align="center">4,769</td>
                <td align="center">4,599</td>
                <td align="center">4,452</td>
                <td align="center">4,439</td>
                <td align="center">4,601</td>
                <td align="center">4,783</td>
                <td align="center">4,149</td>
                <td align="center">0.533</td>
                <td align="center">-0.208</td>
              </tr>
              <tr>
                <td align="left">70-79 years</td>
                <td align="center">6,337</td>
                <td align="center">6,371</td>
                <td align="center">6,583</td>
                <td align="center">6,820</td>
                <td align="center">6,237</td>
                <td align="center">6,343</td>
                <td align="center">5,984</td>
                <td align="center">6,174</td>
                <td align="center">6,496</td>
                <td align="center">5,706</td>
                <td align="center">0.101</td>
                <td align="center">-0.546</td>
              </tr>
              <tr>
                <td align="left">Older than 80 years</td>
                <td align="center">6,591</td>
                <td align="center">6,967</td>
                <td align="center">7,289</td>
                <td align="center">7,778</td>
                <td align="center">7,438</td>
                <td align="center">7,343</td>
                <td align="center">7,318</td>
                <td align="center">7,596</td>
                <td align="center">7,745</td>
                <td align="center">7,306</td>
                <td align="center">0.064</td>
                <td align="center">0.617</td>
              </tr>
              <tr>
                <td align="left">Mean duration of hospitalization (days)</td>
                <td align="center">6.5</td>
                <td align="center">6.4</td>
                <td align="center">6.5</td>
                <td align="center">6.6</td>
                <td align="center">6.7</td>
                <td align="center">6.9</td>
                <td align="center">7.1</td>
                <td align="center">7.3</td>
                <td align="center">7.4</td>
                <td align="center">7.3</td>
                <td align="center">0.004<xref ref-type="table-fn" rid="TFN5">*</xref></td>
                <td align="center">0.960</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN5">
              <label>*</label>
              <p>p &lt; 0.05;</p>
            </fn>
            <fn id="TFN6">
              <label>&#8224;</label>
              <p>P value for trends according to the linear-by-linear association;</p>
            </fn>
            <attrib>Source of data: SUS Information System (DATASUS) and Brazilian Institute of Geography and Statistics (count of 2010)</attrib>
          </table-wrap-foot>
        </table-wrap>
        <p>
          <fig id="f1">
            <label>Figure 1</label>
            <caption>
              <title>Trends in absolute number of hospitalizations from heart failure from 2008 to 2017 in Paraiba (A) and regions of Brazil (B).</title>
            </caption>
            <graphic xlink:href="1678-4170-abc-114-02-0222-80321-gf01.tif"/></fig>
        </p>
        <p>When stratified by age, individuals older than 60 years old corresponded to 71% and 73% of all the cases of HF admissions in Paraiba and Brazil, respectively, with the highest frequency in the age range from 70 to 79 years old.</p>
      </sec>
      <sec>
        <title>Absolute mortality of population</title>
        <p>The absolute mortality from HF of the population showed a non-significant decline from 2008 to 2015 in Paraiba (R = -0.513; p = 0.175; <xref ref-type="table" rid="t2">Table 2</xref>) and Brazil (R = -0.412; p = 0.276; <xref ref-type="table" rid="t3">Table 3</xref>), with no difference by gender. Women represented 53% of deaths in Paraiba and 52% in Brazil. In Paraiba, the decrease in absolute deaths from HF in the population across all age categories was not statistically significant (<xref ref-type="table" rid="t2">Table 2</xref>).</p>
        <p>Between 2008 and 2015, the highest proportion of deaths from HF occurred at the age group of &#8805; 80 years old in both men and women in Paraiba (50% and 59%, respectively) and in Brazil (38% and 52%, respectively). The proportions of deaths from HF at the age &#8805; 60 years old in Paraiba was 87% in men and 90% in women and, in Brazil, 83% in men and 89% in women.</p>
      </sec>
      <sec>
        <title>Population mortality rate</title>
        <p>The mean mortality rate from HF in the population was 19.2/100,000 (&#177;1.09) in Paraiba and 14.0/100,000 (&#177;0.53) in Brazil, with a significant decline of 10.7% (R = -0.751; p = 0.047; <xref ref-type="table" rid="t2">Table 2</xref>) in Paraiba and 7.7% (R = -0.905; p = 0.017; <xref ref-type="table" rid="t3">Table 3</xref>) in Brazil between 2008 and 2015, respectively (<xref ref-type="fig" rid="f2">Figure 2</xref>).</p>
        <p>
          <fig id="f2">
            <label>Figure 2</label>
            <caption>
              <title>Trends in population mortality rate (per 100,000 inhabitants) from heart failure in Paraiba (green) and Brazil (blue) from 2008 to 2015.</title>
            </caption>
            <graphic xlink:href="1678-4170-abc-114-02-0222-80321-gf02.tif"/></fig>
        </p>
      </sec>
      <sec>
        <title>Absolute in-hospital mortality</title>
        <p>The absolute in-hospital HF mortality, between 2008 and 2017, showed a significant decrease of 37.5% in Paraiba (R = -0.824; p = 0.013; <xref ref-type="table" rid="t2">Table 2</xref>; <xref ref-type="fig" rid="f3">Figure 3B</xref>) and a non-significant 14.6% decrease in Brazil (R = -0.504; p = 0.131; <xref ref-type="table" rid="t3">Table 3</xref>; <xref ref-type="fig" rid="f3">Figure 3B</xref>). In the stratified analysis, a significant decrease in the absolute in-hospital deaths from HF was observed for both men and women in Paraiba (R = -0.837; p = 0.012 and R = -0.762; p = 0.022; <xref ref-type="table" rid="t2">Table 2</xref>); this statistically significant trend by sex was not observed in Brazil (<xref ref-type="table" rid="t3">Table 3</xref>).</p>
        <p>
          <fig id="f3">
            <label>Figure 3</label>
            <caption>
              <title>(A) Trend of the in-hospital mortality rate from heart failure in Paraiba (green) and Brazil (blue) from 2008 to 2017; (B) trend of the in-hospital absolute mortality from heart failure in Paraiba (green) and Brazil (blue) from 2008 to 2017.</title>
            </caption>
            <graphic xlink:href="1678-4170-abc-114-02-0222-80321-gf03.tif"/></fig>
        </p>
        <p>Individuals older than 80 years old presented the highest proportion of absolute in-hospital HF deaths in Paraiba and Brazil, from 2008 to 2017, (37% and 32%, respectively) (<xref ref-type="fig" rid="f4">Figure 4</xref>). In Paraiba, there was a statistically significant reduction in in-hospital deaths from HF for the age categories: 20-29 years (p = 0.010), 30-39 years (p = 0.008), 40-49 years (p = 0.029), 50-59 years (p = 0.025) and 70-79 years (p = 0.009) (<xref ref-type="table" rid="t2">Table 2</xref>).</p>
        <p>
          <fig id="f4">
            <label>Figure 4</label>
            <caption>
              <title>(A) Absolute in-hospital deaths from heart failure in Paraiba per age range, from 2008 to 2017. (B) Absolute in-hospital deaths from heart failure in Brazil per age range, from 2008 to 2017.</title>
            </caption>
            <graphic xlink:href="1678-4170-abc-114-02-0222-80321-gf04.tif"/></fig>
        </p>
        <p>Further data on the absolute number of in-hospital deaths from HF per age range in Brazil are specified in <xref ref-type="table" rid="t3">Table 3</xref>.</p>
      </sec>
      <sec>
        <title>In-hospital mortality rate</title>
        <p>The in-hospital HF mortality rate increased significantly by 65.1% in Paraiba (R = 0.917; p = 0.006; <xref ref-type="table" rid="t2">Table 2</xref>), from 6.6% in 2008 to 10.9% in 2017, and by 30.1% in Brazil (R = 0.981; p = 0.003; <xref ref-type="table" rid="t3">Table 3</xref>), from 8.3% in 2008 to 10.8% in 2017 (<xref ref-type="fig" rid="f3">Figure 3A</xref>). The increase in in-hospital mortality rate from HF by gender was also significant for both men and women in Paraiba (R = 0.828; p = 0.013 and R = 0.908; p = 0.006, respectively; <xref ref-type="table" rid="t2">Table 2</xref>). This trend was also observed for both sex in Brazil, in a similar magnitude of effect (R = 0.985; R = 0.980; p = 0.003; <xref ref-type="table" rid="t3">Table 3</xref>).</p>
        <p>The in-hospital HF mortality rate per age range was highest in individuals older than 80 years old, with a mean of 14.7% in Paraiba and 14.5% in Brazil (<xref ref-type="fig" rid="f5">Figure 5</xref>) from 2008 to 2017. In this age range, the in-hospital mortality rate from HF per gender in Paraiba was 12.4% in men and 15.2% in women, and in Brazil, 13.7% in men and 14.9% in women.</p>
        <p>
          <fig id="f5">
            <label>Figure 5</label>
            <caption>
              <title>(A) Trend of the in-hospital mortality rate from heart failure in Paraiba per year and age range, from 2008 to 2017. (B) Trend of the in-hospital mortality rate from heart failure in Brazil per year and age range, from 2008 to 2017.</title>
            </caption>
            <graphic xlink:href="1678-4170-abc-114-02-0222-80321-gf05.tif"/></fig>
        </p>
      </sec>
      <sec>
        <title>Length of hospital stay</title>
        <p>The average length of hospital stay for HF was 5.9 days (&#177;0.8) in Paraiba and 6.9 days (&#177;0.4) in Brazil, with a significant increase of 44% (R = 0.953; p = 0.004; <xref ref-type="table" rid="t2">Table 2</xref>) and 12.3% (R = 0.960; p = 0.004; <xref ref-type="table" rid="t3">Table 3</xref>), respectively, between 2008 and 2017 (<xref ref-type="fig" rid="f6">Figure 6</xref>). In <xref ref-type="table" rid="t4">Table 4</xref>, we present the duration of hospital stay per year, and the associated cost, both in Paraiba and Brazil.</p>
        <p>
          <fig id="f6">
            <label>Figure 6</label>
            <caption>
              <title>Trends in the mean length of stay (days) from heart failure hospitalizations in Paraiba (green) and Brazil (blue) from 2008 to 2017</title>
            </caption>
            <graphic xlink:href="1678-4170-abc-114-02-0222-80321-gf06.tif"/></fig>
        </p>
        <table-wrap id="t4">
          <label>Table 4</label>
          <caption>
            <title>Total cost of HF hospitalizations (US$) and duration of HF admission (days) in Paraiba and Brazil, from 2008 to 2017</title>
          </caption>
          <table frame="hsides" rules="groups">
            <colgroup>
              <col width="20%"/>
              <col width="20%"/>
              <col width="20%"/>
              <col width="20%"/>
              <col width="20%"/>
            </colgroup>
            <thead>
              <tr>
                <th align="left" style="border-bottom-width:thin;border-bottom-style:solid">&#160;</th>
                <th align="center" colspan="2" style="border-bottom-width:thin;border-bottom-style:solid">PARA&#205;BA</th>
                <th align="center" colspan="2" style="border-bottom-width:thin;border-bottom-style:solid">BRAZIL</th>
              </tr>
              <tr>
                <th align="left">Year</th>
                <th align="center">Total cost with hospitalizations (US$)</th>
                <th align="center">Duration of admission (days)</th>
                <th align="center">Total cost with hospitalizations (US$)</th>
                <th align="center">Duration of admission (days)</th>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td align="left">2008</td>
                <td align="center">1,762,825.91</td>
                <td align="center">5</td>
                <td align="center">77,940,473.93</td>
                <td align="center">6.5</td>
              </tr>
              <tr>
                <td align="left">2009</td>
                <td align="center">2,286,531.90</td>
                <td align="center">5.2</td>
                <td align="center">89,837,575.25</td>
                <td align="center">6.4</td>
              </tr>
              <tr>
                <td align="left">2010</td>
                <td align="center">2,541,429.71</td>
                <td align="center">5.3</td>
                <td align="center">92,835,802.31</td>
                <td align="center">6.5</td>
              </tr>
              <tr>
                <td align="left">2011</td>
                <td align="center">2,378,139.40</td>
                <td align="center">5.5</td>
                <td align="center">93,939,042.90</td>
                <td align="center">6.6</td>
              </tr>
              <tr>
                <td align="left">2012</td>
                <td align="center">1,939,284.53</td>
                <td align="center">5.6</td>
                <td align="center">91,509,632.22</td>
                <td align="center">6.7</td>
              </tr>
              <tr>
                <td align="left">2013</td>
                <td align="center">1,694,005.09</td>
                <td align="center">5.6</td>
                <td align="center">93,561,446.18</td>
                <td align="center">6.9</td>
              </tr>
              <tr>
                <td align="left">2014</td>
                <td align="center">1,578,506.24</td>
                <td align="center">6.1</td>
                <td align="center">96,199,113.56</td>
                <td align="center">7.1</td>
              </tr>
              <tr>
                <td align="left">2015</td>
                <td align="center">1,233,302.85</td>
                <td align="center">6.5</td>
                <td align="center">99,069,494.68</td>
                <td align="center">7.3</td>
              </tr>
              <tr>
                <td align="left">2016</td>
                <td align="center">1,249,580.27</td>
                <td align="center">7.2</td>
                <td align="center">102,181,019.88</td>
                <td align="center">7.4</td>
              </tr>
              <tr>
                <td align="left">2017</td>
                <td align="center">1,103,600.05</td>
                <td align="center">7.2</td>
                <td align="center">85,390,241.41</td>
                <td align="center">7.3</td>
              </tr>
              <tr>
                <td align="left">Total</td>
                <td align="center">17,767,205.95</td>
                <td align="center">5.9 &#177; 0.8 (mean &#177; SD)</td>
                <td align="center">922,463,842.32</td>
                <td align="center">6.9 &#177; 0.4 (mean &#177; SD)</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN7">
              <p>SD: standard deviation;</p>
            </fn>
            <attrib>Source of data: SUS Information System (DATASUS) and Brazilian Institute of Geography and Statistics (count of 2010)</attrib>
          </table-wrap-foot>
        </table-wrap>
      </sec>
    </sec>
    <sec sec-type="discussion">
      <title>Discussion</title>
      <p>To our knowledge, this is the first study to describe the trends of HF epidemiology in a less developed region of Brazil. Information regarding the incidence, prevalence, morbidity and mortality of HF in Latin America and the Caribbean (LAC) are heterogeneous and scarce. Most of the data come from South America (92%), with 86% of the studies conducted in Brazil and Argentina.<xref ref-type="bibr" rid="B10">10</xref> In Brazil, most of the published data come from developed areas, the Southeast and South regions.</p>
      <p>HF was the leading cause of hospitalizations among cardiovascular diseases in Paraiba and Brazil, and corresponded to 2.54% and 2.25% of all admissions, respectively. Similarly, in the U.S., HF was the cause of more than 1 million admissions per year from 2001 to 2009,<xref ref-type="bibr" rid="B11">11</xref> and represented 1-2% of all hospitalizations.<xref ref-type="bibr" rid="B3">3</xref></p>
      <p>Fang et al.<xref ref-type="bibr" rid="B12">12</xref> performed a study to determine the trends in HF in the U.S. using the National Hospital Discharge Survey data from 1979 to 2004, and observed an increase of 185% in the absolute number of HF admissions (from 409,000 to 1,166,000) and the HF hospitalization rates (per 100,000) increased from 219 to 390 during the same period. Other authors, however, have reported that the number of primary hospitalizations for HF have been decreasing in the U.S. between 1.0% to 4.3% per year since 2001.<xref ref-type="bibr" rid="B11">11</xref><sup>,</sup><xref ref-type="bibr" rid="B13">13</xref> In the LAC, Godoy et al.<xref ref-type="bibr" rid="B14">14</xref> showed a 32% decrease in HF admissions, between 1992-1993 and 2008-2009, which is consistent with our findings of a 34% decrease in the absolute number of hospitalizations for HF in Brazil, and 62% in Paraiba. This observed reduction can be a sign of improvement in the overall management of the risk factors for HF,<xref ref-type="bibr" rid="B4">4</xref> a decrease in the incidence of ischemic heart disease,<xref ref-type="bibr" rid="B15">15</xref> and an improvement in HF management.<xref ref-type="bibr" rid="B16">16</xref></p>
      <p>Hospitalizations for HF in Paraiba and Brazil were more common for individuals between the ages of 70 to 79 years old. Individuals older than 60 years old represented 71% and 73% of admissions for HF in Paraiba and Brazil, respectively; this is similar to the frequency (70%) reported in previous studies in LAC and U.S..<xref ref-type="bibr" rid="B2">2</xref><sup>,</sup><xref ref-type="bibr" rid="B4">4</xref> In Paraiba and in Brazil, the proportion of women hospitalized for HF was 48% vs 49%, similar to studies in the U.S., with 40% to 50% of women.<xref ref-type="bibr" rid="B3">3</xref><sup>,</sup><xref ref-type="bibr" rid="B17">17</xref> A small study performed in a community in Brazil reported that 58% of hospitalized patients with HF were women.<xref ref-type="bibr" rid="B18">18</xref> Also, the I Brazilian Registry of Heart Failure (BREATHE registry)<xref ref-type="bibr" rid="B8">8</xref> describes that 60% of 1,263 admissions for HF in 51 centers of Brazil were women.</p>
      <p>In our study, mean mortality rate for HF in the population between 2008 to 2015 was 19.2/100,000 (&#177;1.09) cases in Paraiba and 14.0/100,000 (&#177;0.53) cases in Brazil, with a decline of 10.7% and 7.7%, respectively. A decrease in the mortality rate for HF was also reported in Brazil and Argentina: in Sao Paulo, Brazil&#8217;s largest city, there was a 29% decrease, from 19.1/100,000 (1992-1993) to 13.6/100,000 (2008-2009);<xref ref-type="bibr" rid="B14">14</xref> in Argentina, a nationwide study showed a reduction of 23% in the population HF mortality rate from 1995 to 2005.<xref ref-type="bibr" rid="B10">10</xref><sup>,</sup><xref ref-type="bibr" rid="B19">19</xref> In the U.S., Go et al.<xref ref-type="bibr" rid="B20">20</xref> compared the absolute number of HF deaths from 1995 to 2010, and found a decrease of 2.8% (287,000 vs 279,000), which potentially represents a significant decrease in the mortality rate, given the increase in the US population over 15 years.</p>
      <p>Our study reports a mean in-hospital mortality rate for HF in Paraiba of 9.2% between 2008 and 2017. A prospective study performed in 51 centers from all the Brazilian regions, only with patients hospitalized due to acute HF, reported a total of 12.6% deaths in 1,263 hospitalized patients.<xref ref-type="bibr" rid="B8">8</xref> In the LAC, a meta-analysis of 37 studies revealed a similar in-hospital mortality of 11.7%.<xref ref-type="bibr" rid="B10">10</xref></p>
      <p>Our study demonstrated an increase in the in-hospital mortality rate for HF, both in Paraiba and in Brazil (65% and 30%, respectively), between 2008 and 2017. Godoy et al.,<xref ref-type="bibr" rid="B14">14</xref> between 1992-1993 and 2008-2009, also reported a 15% increase in the previous 15% in-hospital mortality rate in Brazil. In the U.S., however, the in-hospital mortality rate decreased from 4.5% in 2001 to 2.9% in 2014 according to a study that included patients with a primary diagnosis of HF.<xref ref-type="bibr" rid="B13">13</xref> The decrease in the number of hospitalizations for HF during the study period, both in Paraiba and Brazil, is the most likely reason for the increased in-hospital mortality rate. Another plausible explanation could be the increased survival of HF patients, leading to a higher number of elderly patients, with more advanced HF and multiple comorbidities, and increased risk of death during hospitalization. Lastly, it is important to consider the lack of advanced therapies in less developed areas, as mechanical devices and heart transplantation, contributing to this trend of increased HF mortality rate in Paraiba, Brazil and LAC.</p>
      <p>Although there was an increase in the in-hospital mortality rate, absolute in-hospital mortality showed a significant decrease of 37.5% in Paraiba and 14.6% in Brazil for the same period. In the U.S., Bueno et al.<xref ref-type="bibr" rid="B21">21</xref> also observed a 50% decrease in the in-hospital mortality for HF in a population of elderly Medicare patients, from 1993 to 2008, and Ni and Xu,<xref ref-type="bibr" rid="B22">22</xref> a 30% decrease.</p>
      <p>Women represented 53% and 52% of the absolute mortality for HF in Paraiba and Brazil, respectively. The in-hospital mortality for HF in Paraiba had a similar proportion of women (50.5%). In the U.S., in 2010, 54.6% of all HF deaths happened in women.<xref ref-type="bibr" rid="B20">20</xref> Hsich et al.<xref ref-type="bibr" rid="B23">23</xref> observed no difference in the in-hospital mortality between women and men considering both the reduced and preserved ejection fraction groups.</p>
      <p>Between 2008 and 2017, the mean duration of hospitalization for HF was 5.9 (&#177;0.8) days in Paraiba and 6.8 (&#177;0.4) days in Brazil, with an increase of 44% and 12.3%, respectively. In the LAC, Bocchi et al.<sup>(2, 24)</sup> found a mean hospital stay of 5.8 days between 1998 and 2012. Ciapponi et al.<xref ref-type="bibr" rid="B10">10</xref> reported an average of 7 days in 18 studies, and Godoy et al.<xref ref-type="bibr" rid="B14">14</xref> found an increase of 25% in the length of stay, from 8.8 (1992-1993) to 11.3 days (2008-2009) in Brazil. In the U.S., two authors reported a decrease in the length of stay due to HF, from 8.8 to 6.3 days (1993-2008)<xref ref-type="bibr" rid="B21">21</xref> and from 6.8 days (1999-2000) to 6.4 days (2007-2008).<xref ref-type="bibr" rid="B4">4</xref></p>
      <p>In the U.S., the per capita cost with healthcare was greater than the per capita gross domestic product of Paraiba (US$8,364.00 and US$3,594.94, respectively).<xref ref-type="bibr" rid="B24">24</xref> The lower socioeconomic status in Paraiba may represent a risk factor for the high morbidity and mortality observed in our study, because the population has limited access to effective HF treatment.<xref ref-type="bibr" rid="B24">24</xref> In the U.S., 52.5% of people with a household income less than US$10,000 suffer from a cardiovascular disease<xref ref-type="bibr" rid="B20">20</xref><sup>,</sup><xref ref-type="bibr" rid="B25">25</xref> and Eapen et al.<xref ref-type="bibr" rid="B26">26</xref> found that a higher income was associated with lower odds of 30-day mortality after a HF admission.</p>
      <sec>
        <title>Limitations</title>
        <p>This is a retrospective and observational study, and the lack of patient-level data limited our ability to establish relationship between variables. Since our data was derived from a national database, it is likely that underreporting and misreporting of data have occurred. Also, since readmissions are not considered in the total number of HF hospitalizations, in-hospital mortality rate may have been underestimated.</p>
      </sec>
    </sec>
    <sec sec-type="conclusions">
      <title>Conclusions</title>
      <p>This is the first study to analyze the epidemiology of HF in Paraiba, a less developed state of Brazil, and to compare the results with national and international data. Over the last 10 years, the increase of the in-hospital mortality rate for HF in Paraiba and in Brazil followed the LAC trend, whereas the increase in the duration of hospitalization for HF is opposite to the decrease seen in the U.S.. In Paraiba and Brazil, we observed a decrease in admission for HF as primary diagnosis as well as in the absolute in-hospital deaths for HF, agreeing with the LAC and U.S.. More than 87% of the HF deaths in Paraiba and Brazil involved patients older than 60 years old. There was a higher frequency of woman admitted for HF, both in Paraiba and Brazil, with similar mortality rates when compared to men. Since women are generally underrepresented in clinical trials, there is a need for more studies focusing on that population. Hospital-based clinical studies should be performed to identify the causes for the trend of increase in in-hospital mortality rate for HF.</p>
    </sec>
  </body>
  <back>
    <fn-group>
      <fn fn-type="financial-disclosure">
        <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 thesis or dissertation work.</p>
      </fn>
      <fn fn-type="other">
        <p>
          <bold>Ethics approval and consent to participate</bold>
        </p>
        <p>This article does not contain any studies with human participants or animals performed by any of the authors.</p>
      </fn>
    </fn-group>
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  <sub-article article-type="translation" id="s1" xml:lang="pt">
    <front-stub>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Artigo Original</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Insufici&#234;ncia Card&#237;aca no Brasil Subdesenvolvido: An&#225;lise de Tend&#234;ncia de Dez Anos</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-7443-5029</contrib-id>
          <name>
            <surname>Fernandes</surname>
            <given-names>Amanda D. F.</given-names>
          </name>
          <xref ref-type="aff" rid="aff5">1</xref>
          <xref ref-type="corresp" rid="c2"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Fernandes</surname>
            <given-names>Gilson C.</given-names>
          </name>
          <xref ref-type="aff" rid="aff6">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Mazza</surname>
            <given-names>Manuel Rivera</given-names>
          </name>
          <xref ref-type="aff" rid="aff5">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Knijnik</surname>
            <given-names>Leonardo M.</given-names>
          </name>
          <xref ref-type="aff" rid="aff5">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Fernandes</surname>
            <given-names>Gustavo Soares</given-names>
          </name>
          <xref ref-type="aff" rid="aff7">3</xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-8656-870X</contrib-id>
          <name>
            <surname>Vilela</surname>
            <given-names>Andre Telis de</given-names>
          </name>
          <xref ref-type="aff" rid="aff8">4</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Badiye</surname>
            <given-names>Amit</given-names>
          </name>
          <xref ref-type="aff" rid="aff6">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Chaparro</surname>
            <given-names>Sandra V.</given-names>
          </name>
          <xref ref-type="aff" rid="aff6">2</xref>
        </contrib>
      </contrib-group>
      <aff id="aff5">
        <label>1</label>
        <institution content-type="original">University of Miami Miller School of Medicine - Department of Medicine, Miami, Florida - EUA</institution>
      </aff>
      <aff id="aff6">
        <label>2</label>
        <institution content-type="original">University of Miami Miller School of Medicine - Division of Cardiology, Miami, Florida - EUA</institution>
      </aff>
      <aff id="aff7">
        <label>3</label>
        <institution content-type="original">Centro Universitario de Joao Pessoa, Jo&#227;o Pessoa, PB - Brasil</institution>
      </aff>
      <aff id="aff8">
        <label>4</label>
        <institution content-type="original">Universidade Federal da Paraiba, Jo&#227;o Pessoa, PB - Brasil</institution>
      </aff>
      <author-notes>
        <corresp id="c2"><bold>Correspond&#234;ncia: Amanda D. F. Fernandes,</bold> University of Miami Miller School of Medicine - Department of Medicine - 1600 N.W. 10th Avenue Miami Fl&#243;rida 33136 - Estados Unidos. E-mail: <email>amandadantasff@gmail.com</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: Fernandes ADF; Obten&#231;&#227;o de dados: Fernandes ADF, Knijnik LM, Fernandes GS; An&#225;lise e interpreta&#231;&#227;o dos dados: Fernandes ADF, Fernandes GC, Knijnik LM; An&#225;lise estat&#237;stica: Fernandes ADF, Fernandes GC, Mazza MR; Reda&#231;&#227;o do manuscrito: Fernandes ADF, Fernandes GC, Mazza MR, Knijnik LM, Fernandes GS; Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do intelectual importante: Fernandes ADF, Fernandes GC, Mazza MR, Knijnik LM, Vilela AT, Badiye A, Chaparro SV.</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>
      <abstract>
        <title>Resumo</title>
        <sec>
          <title>Fundamento:</title>
          <p>Dados sobre a epidemiologia da insufici&#234;ncia card&#237;aca (IC) em &#225;reas pouco desenvolvidas s&#227;o escassos.</p>
        </sec>
        <sec>
          <title>Objetivos:</title>
          <p>Nosso objetivo foi determinar a morbidade e a mortalidade por IC na Para&#237;ba e no Brasil, e sua tend&#234;ncia em dez anos.</p>
        </sec>
        <sec>
          <title>M&#233;todos:</title>
          <p>Realizou-se uma busca retrospectiva de 2008 a 2017 utilizando-se o banco de dados do DATASUS incluindo pacientes com idade &#8805; 15 anos, com diagn&#243;stico prim&#225;rio de IC. Os dados da morbimortalidade por IC foram coletados e estratificados por ano, sexo e idade. Foram realizados correla&#231;&#227;o de Pearson e teste para tend&#234;ncias de Mantel-Haenzsel. Um n&#237;vel de 5% foi definido como estatisticamente significativo.</p>
        </sec>
        <sec>
          <title>Resultados:</title>
          <p>De 2008 a 2017, as interna&#231;&#245;es por IC diminu&#237;ram 62% (p = 0,004) na Para&#237;ba, e 34% (p = 0,004) no Brasil. A taxa de mortalidade hospitalar aumentou na Para&#237;ba e no Brasil [65,1% (p = 0,006) e 30,1% (p = 0,003), respectivamente], mas a mortalidade hospitalar em n&#250;meros absolutos apresentou uma diminui&#231;&#227;o significativa somente na Para&#237;ba [37,5% (p = 0,013)], o que foi mantido ap&#243;s a estratifica&#231;&#227;o por idade, exceto para os grupos 15-19, 60-69 e &gt; 80 anos. Observou-se um aumento no per&#237;odo de interna&#231;&#227;o [44% (p = 0,004) na Para&#237;ba e 12,3% (p = 0,004) no Brasil]. De 2008 a 2015, a taxa de mortalidade por IC na popula&#231;&#227;o diminuiu 10,7% na Para&#237;ba (p = 0,047) e 7,7% (p = 0,017) no Brasil<bold>.</bold></p>
        </sec>
        <sec>
          <title>Conclus&#245;es:</title>
          <p>Apesar de a taxa de mortalidade por IC estar diminuindo na Para&#237;ba e no Brasil, observou-se um aumento na taxa de mortalidade hospitalar e na dura&#231;&#227;o da interna&#231;&#227;o por IC. Devem ser realizados estudos cl&#237;nicos em hospitais para serem identificadas as causas dessa tend&#234;ncia de aumento.</p>
        </sec>
      </abstract>
      <kwd-group xml:lang="pt">
        <title>Palavras-chave:</title>
        <kwd>Insufici&#234;ncia Card&#237;aca/fisiopatologia</kwd>
        <kwd>Insufici&#234;ncia Card&#237;aca/mortalidade</kwd>
        <kwd>Insufici&#234;ncia Card&#237;aca/epidemiologia</kwd>
        <kwd>Comorbidade</kwd>
        <kwd>Insufici&#234;ncia Card&#237;aca/tend&#234;ncias</kwd>
        <kwd>Hospitaliza&#231;&#227;o</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <sec sec-type="intro">
        <title>Introdu&#231;&#227;o</title>
        <p>A insufici&#234;ncia card&#237;aca (IC) &#233; a principal causa de interna&#231;&#245;es hospitalares nos Estados Unidos em pacientes com idade superior a 65 anos,<xref ref-type="bibr" rid="B1">1</xref><sup>,</sup><xref ref-type="bibr" rid="B2">2</xref> e afeta 26 milh&#245;es de pessoas em todo o mundo segundo estimativas.<xref ref-type="bibr" rid="B3">3</xref> Sua preval&#234;ncia tem aumentado rapidamente devido ao envelhecimento da popula&#231;&#227;o.<xref ref-type="bibr" rid="B1">1</xref><sup>,</sup><xref ref-type="bibr" rid="B4">4</xref> Uma maior expectativa de vida tem sido atingida gra&#231;as &#224; ades&#227;o ao tratamento medicamentoso, ao uso de dispositivos de assist&#234;ncia ventricular (DAV) e a um aumento no n&#250;mero de transplantes card&#237;acos.<xref ref-type="bibr" rid="B1">1</xref></p>
        <p>A Para&#237;ba &#233; um dos nove estados na regi&#227;o nordeste do Brasil e teve uma popula&#231;&#227;o estimada de 4 025 558 habitantes em 2017, o que corresponde ao 13&#186; estado em popula&#231;&#227;o entre os 27 estados do pa&#237;s. O produto interno bruto per capita da Para&#237;ba foi de 3 594,94 d&#243;lares americanos em 2010, correspondendo ao quarto estado mais pobre do pa&#237;s, e o &#237;ndice de desenvolvimento humano em 2014 foi de 0,701, o sexto mais baixo do pa&#237;s.<xref ref-type="bibr" rid="B5">5</xref><sup>,</sup><xref ref-type="bibr" rid="B6">6</xref> Dados sobre a epidemiologia da IC em pa&#237;ses subdesenvolvidos s&#227;o ainda limitados e baseados principalmente em coortes de pacientes hospitalizados ou ensaios cl&#237;nicos.<xref ref-type="bibr" rid="B2">2</xref> N&#227;o existem, no Brasil, dados sobre a epidemiologia da IC na Para&#237;ba, e existem poucos estudos que relatem os n&#250;meros da IC na regi&#227;o nordeste do Brasil.<xref ref-type="bibr" rid="B7">7</xref><sup>,</sup><xref ref-type="bibr" rid="B8">8</xref></p>
        <p>Um melhor entendimento da epidemiologia da IC em &#225;reas subdesenvolvidas do Brasil, tal como a Para&#237;ba, por meio de estudos populacionais, poderia levar a um planejamento em sa&#250;de mais efetivo e adequado. O objetivo deste estudo foi descrever e realizar uma an&#225;lise de tend&#234;ncia de 10 anos da morbidade e da mortalidade da IC no estado da Para&#237;ba e no Brasil.</p>
      </sec>
      <sec sec-type="methods">
        <title>M&#233;todos</title>
        <sec>
          <title>Modelo do estudo</title>
          <p>Trata-se de um estudo populacional de an&#225;lise de s&#233;rie temporal utilizando o Sistema de Informa&#231;&#245;es Hospitalares (SIH/SUS), dispon&#237;vel no banco de dados do DATASUS (Departamento de Inform&#225;tica do Sistema &#218;nico de Sa&#250;de - SUS).<xref ref-type="bibr" rid="B6">6</xref> O DATASUS &#233; respons&#225;vel pela administra&#231;&#227;o de todas as informa&#231;&#245;es sobre sa&#250;de e finan&#231;as declaradas por todos os estados e cidades e pelo Distrito Federal. Essa base de dados compila informa&#231;&#245;es sobre assist&#234;ncia &#224; sa&#250;de, epidemiologia, morbidade e demografia.</p>
        </sec>
        <sec>
          <title>Popula&#231;&#227;o do estudo</title>
          <p>A popula&#231;&#227;o de interesse foi composta por brasileiros com idade superior a 15 anos que utilizaram qualquer servi&#231;o de sa&#250;de sob o diagn&#243;stico prim&#225;rio de IC, representado pelo c&#243;digo I50 da d&#233;cima revis&#227;o da Classifica&#231;&#227;o Internacional de Doen&#231;as (CID-10), entre 2008 e 2017.</p>
        </sec>
        <sec>
          <title>Vari&#225;veis</title>
          <p>Foram extra&#237;dos dados epidemiol&#243;gicos da IC, incluindo mortalidade absoluta e relativa da popula&#231;&#227;o, mortalidade hospitalar (n&#250;meros absolutos), taxa de mortalidade hospitalar, n&#250;mero de interna&#231;&#245;es e per&#237;odo de interna&#231;&#227;o. As vari&#225;veis foram estratificadas por ano, sexo e grupos et&#225;rios (15-19, 20-29, 30-39, 40-49, 50-59, 60-69, 70-79 e &#8805; 80 anos). Dados hospitalares do per&#237;odo entre 2008 e 2017, e dados populacionais do per&#237;odo entre 2008 e 2015 estavam dispon&#237;veis. Utilizou-se &#250;ltimo censo populacional do Instituto Brasileiro de Geografia e Estat&#237;stica (IBGE) de 2010.<xref ref-type="bibr" rid="B5">5</xref></p>
        </sec>
        <sec>
          <title>An&#225;lise dos dados</title>
          <p>As vari&#225;veis categ&#243;ricas foram expressas em frequ&#234;ncias e as vari&#225;veis cont&#237;nuas em m&#233;dia &#177; desvivo padr&#227;o (DP). A taxa de mortalidade hospitalar causada por IC foi obtida dividindo-se o n&#250;mero de todas as mortes hospitalares por IC na Para&#237;ba ou no Brasil pelo n&#250;mero de hospitaliza&#231;&#245;es por IC no ano correspondente. A taxa de mortalidade populacional por IC foi calculada dividindo-se o n&#250;mero de todas as mortes por IC na Para&#237;ba ou no Brasil pela respectiva popula&#231;&#227;o no ano correspondente.</p>
          <p>As an&#225;lises foram realizadas utilizando o programa <italic>Statistical Package for the Social Sciences</italic> (SPSS) vers&#227;o 21.0 (SPPS Inc., Chicago, USA). O teste de Shapiro-Wilk foi usado para avaliar a normalidade das distribui&#231;&#245;es dos dados para as an&#225;lises posteriores. A correla&#231;&#227;o de Pearson foi usada para avaliar a correla&#231;&#227;o entre vari&#225;veis num&#233;ricas com distribui&#231;&#227;o normal. O teste do qui-quadrado foi realizado por tabela de conting&#234;ncia e pelo teste de tend&#234;ncia linear de Mantel-Haenzsel, o qual corresponde ao teste de Cochran-Armitage dispon&#237;vel em outros pacotes estat&#237;sticos.<xref ref-type="bibr" rid="B9">9</xref> O n&#237;vel de signific&#226;ncia estabelecido foi de 5%.</p>
        </sec>
      </sec>
      <sec sec-type="results">
        <title>Resultados</title>
        <p>A estat&#237;stica descritiva das vari&#225;veis est&#225; apresentada na <xref ref-type="table" rid="t5">Tabela 1</xref>.</p>
        <table-wrap id="t5">
          <label>Tabela 1</label>
          <caption>
            <title>Estat&#237;sticas descritivas da epidemiologia da Insufici&#234;ncia Card&#237;aca na Para&#237;ba, de 2008 a 2017</title>
          </caption>
          <table frame="hsides" rules="groups">
            <colgroup>
              <col width="25%"/>
              <col width="25%"/>
              <col width="25%"/>
              <col width="25%"/>
            </colgroup>
            <thead>
              <tr>
                <th align="left">Vari&#225;veis</th>
                <th align="center">M&#233;dia</th>
                <th align="center">Desvio padr&#227;o</th>
                <th align="center">Shapiro-Wilk signific&#226;ncia<xref ref-type="table-fn" rid="TFN8">*</xref></th>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td align="left">&#211;bitos (popula&#231;&#227;o) <sup><xref ref-type="table-fn" rid="TFN9">&#8224;</xref></sup></td>
                <td align="center">739,88</td>
                <td align="center">32,92</td>
                <td align="center">0,385</td>
              </tr>
              <tr>
                <td align="left">Mulheres</td>
                <td align="center">387,88</td>
                <td align="center">24,07</td>
                <td align="center">0,916</td>
              </tr>
              <tr>
                <td align="left">Homens</td>
                <td align="center">349,63</td>
                <td align="center">17,71</td>
                <td align="center">0,099</td>
              </tr>
              <tr>
                <td align="left">&#211;bitos (no hospital)</td>
                <td align="center">474,50</td>
                <td align="center">95,52</td>
                <td align="center">0,324</td>
              </tr>
              <tr>
                <td align="left">Mulheres</td>
                <td align="center">238,80</td>
                <td align="center">46,15</td>
                <td align="center">0,763</td>
              </tr>
              <tr>
                <td align="left">Homens</td>
                <td align="center">234,70</td>
                <td align="center">52,04</td>
                <td align="center">0,161</td>
              </tr>
              <tr>
                <td align="left">Taxa de mortalidade populacional (por 100.000) <sup><xref ref-type="table-fn" rid="TFN9">&#8224;</xref></sup></td>
                <td align="center">19,16</td>
                <td align="center">1,09</td>
                <td align="center">0,775</td>
              </tr>
              <tr>
                <td align="left">Taxa de mortalidade hospitalar (por 100)</td>
                <td align="center">9,76</td>
                <td align="center">1,84</td>
                <td align="center">0,659</td>
              </tr>
              <tr>
                <td align="left">N&#250;mero de admiss&#245;es</td>
                <td align="center">5117,20</td>
                <td align="center">1805,13</td>
                <td align="center">0,176</td>
              </tr>
              <tr>
                <td align="left">Tempo m&#233;dio de interna&#231;&#227;o (dias)</td>
                <td align="center">5,92</td>
                <td align="center">0,80</td>
                <td align="center">0,121</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN8">
              <label>*</label>
              <p>No teste de Shapiro-Wilk, a hip&#243;tese nula &#233; que a popula&#231;&#227;o segue uma distribui&#231;&#227;o normal; se p &lt; 0,05, os dados n&#227;o s&#227;o normalmente distribu&#237;dos;</p>
            </fn>
            <fn id="TFN9">
              <label>&#8224;</label>
              <p>Intervalo do ano: 2008-2015;</p>
            </fn>
            <attrib>Fonte dos dados: Sistema de Informa&#231;&#227;o do SUS (DATASUS) e Instituto Brasileiro de Geografia e Estat&#237;stica (2010).</attrib>
          </table-wrap-foot>
        </table-wrap>
        <sec>
          <title>Hospitaliza&#231;&#245;es</title>
          <p>O n&#250;mero total de interna&#231;&#245;es hospitalares por IC na Para&#237;ba entre 2008 e 2017 foi 51 172, representando a principal causa de interna&#231;&#245;es por doen&#231;as cardiovasculares (29,4%), seguido por outras doen&#231;as card&#237;acas isqu&#234;micas (13%), acidente vascular cerebral (11%), hipertens&#227;o prim&#225;ria (10%), e infarto agudo do mioc&#225;rdio (5%). Durante o mesmo per&#237;odo, a IC tamb&#233;m foi a principal causa cardiovascular de hospitaliza&#231;&#245;es no Brasil, com 2 380 133 casos (21%). A IC foi respons&#225;vel por 2,54% e 2,25% de todas as causas de interna&#231;&#245;es hospitalares na Para&#237;ba e no Brasil, respectivamente.</p>
          <p>Uma tend&#234;ncia decrescente no n&#250;mero absoluto de hospitaliza&#231;&#245;es por IC na Para&#237;ba e no Brasil foi observada entre 2008 e 2017, correspondendo a um decr&#233;scimo de 62% (R = -0,970; p = 0,004; <xref ref-type="table" rid="t6">Tabela 2</xref>; <xref ref-type="fig" rid="f7">Figura 1A</xref>) e 34% (R = -0,964; p = 0,004; <xref ref-type="table" rid="t7">Tabela 3</xref>; <xref ref-type="fig" rid="f7">Figura 1B</xref>), respectivamente. A frequ&#234;ncia de homens internados por IC na Para&#237;ba foi de 52% e no Brasil de 51%.</p>
          <table-wrap id="t6">
            <label>Tabela 2</label>
            <caption>
              <title>Tend&#234;ncias da insufici&#234;ncia card&#237;aca na Para&#237;ba, de 2008 a 2017</title>
            </caption>
            <table frame="hsides" rules="groups">
              <colgroup>
                <col width="7%"/>
                <col width="7%"/>
                <col width="7%"/>
                <col width="7%"/>
                <col width="7%"/>
                <col width="7%"/>
                <col width="7%"/>
                <col width="7%"/>
                <col width="7%"/>
                <col width="7%"/>
                <col width="7%"/>
                <col width="7%"/>
                <col width="7%"/>
              </colgroup>
              <thead>
                <tr>
                  <th align="left">Vari&#225;veis</th>
                  <th align="center">2008</th>
                  <th align="center">2009</th>
                  <th align="center">2010</th>
                  <th align="center">2011</th>
                  <th align="center">2012</th>
                  <th align="center">2013</th>
                  <th align="center">2014</th>
                  <th align="center">2015</th>
                  <th align="center">2016</th>
                  <th align="center">2017</th>
                  <th align="center">Valores de p para tend&#234;ncias<xref ref-type="table-fn" rid="TFN10">*</xref><sup><xref ref-type="table-fn" rid="TFN11">&#8224;</xref></sup></th>
                  <th align="center">Pearson (R)</th>
                </tr>
              </thead>
              <tbody>
                <tr>
                  <td align="left">N&#250;mero de mortes (popula&#231;&#227;o)</td>
                  <td align="center">722</td>
                  <td align="center">777</td>
                  <td align="center">772</td>
                  <td align="center">753</td>
                  <td align="center">719</td>
                  <td align="center">768</td>
                  <td align="center">725</td>
                  <td align="center">683</td>
                  <td align="center">------</td>
                  <td align="center">------</td>
                  <td align="center">0,175</td>
                  <td align="center">-0,513</td>
                </tr>
                <tr>
                  <td align="left">Mulheres</td>
                  <td align="center">365</td>
                  <td align="center">398</td>
                  <td align="center">390</td>
                  <td align="center">413</td>
                  <td align="center">386</td>
                  <td align="center">421</td>
                  <td align="center">383</td>
                  <td align="center">347</td>
                  <td align="center">------</td>
                  <td align="center">------</td>
                  <td align="center">0,665</td>
                  <td align="center">-0,164</td>
                </tr>
                <tr>
                  <td align="left">Homens</td>
                  <td align="center">351</td>
                  <td align="center">374</td>
                  <td align="center">379</td>
                  <td align="center">337</td>
                  <td align="center">332</td>
                  <td align="center">347</td>
                  <td align="center">341</td>
                  <td align="center">336</td>
                  <td align="center">------</td>
                  <td align="center">------</td>
                  <td align="center">0,130</td>
                  <td align="center">-0,573</td>
                </tr>
                <tr>
                  <td align="left">N&#250;mero de &#243;bitos (no hospital)</td>
                  <td align="center">472</td>
                  <td align="center">588</td>
                  <td align="center">581</td>
                  <td align="center">561</td>
                  <td align="center">551</td>
                  <td align="center">462</td>
                  <td align="center">461</td>
                  <td align="center">374</td>
                  <td align="center">378</td>
                  <td align="center">317</td>
                  <td align="center">0,013<xref ref-type="table-fn" rid="TFN10">*</xref></td>
                  <td align="center">-0,824</td>
                </tr>
                <tr>
                  <td align="left">Mulheres</td>
                  <td align="center">220</td>
                  <td align="center">310</td>
                  <td align="center">294</td>
                  <td align="center">282</td>
                  <td align="center">265</td>
                  <td align="center">235</td>
                  <td align="center">224</td>
                  <td align="center">207</td>
                  <td align="center">188</td>
                  <td align="center">173</td>
                  <td align="center">0,022<xref ref-type="table-fn" rid="TFN10">*</xref></td>
                  <td align="center">-0,762</td>
                </tr>
                <tr>
                  <td align="left">Homens</td>
                  <td align="center">252</td>
                  <td align="center">278</td>
                  <td align="center">287</td>
                  <td align="center">279</td>
                  <td align="center">286</td>
                  <td align="center">227</td>
                  <td align="center">237</td>
                  <td align="center">167</td>
                  <td align="center">190</td>
                  <td align="center">144</td>
                  <td align="center">0,012<xref ref-type="table-fn" rid="TFN10">*</xref></td>
                  <td align="center">-0,837</td>
                </tr>
                <tr>
                  <td align="left">Taxa de mortalidade (popula&#231;&#227;o)</td>
                  <td align="center">19,25</td>
                  <td align="center">20,53</td>
                  <td align="center">20,21</td>
                  <td align="center">19,55</td>
                  <td align="center">18,51</td>
                  <td align="center">19,62</td>
                  <td align="center">18,38</td>
                  <td align="center">17,19</td>
                  <td align="center">------</td>
                  <td align="center">------</td>
                  <td align="center">0,047<xref ref-type="table-fn" rid="TFN10">*</xref></td>
                  <td align="center">-0,751</td>
                </tr>
                <tr>
                  <td align="left">Taxa de mortalidade (intra-hospitalar)</td>
                  <td align="center">6,60</td>
                  <td align="center">8,50</td>
                  <td align="center">7,90</td>
                  <td align="center">8,50</td>
                  <td align="center">10,10</td>
                  <td align="center">9,8</td>
                  <td align="center">11,20</td>
                  <td align="center">12,00</td>
                  <td align="center">12,10</td>
                  <td align="center">10,90</td>
                  <td align="center">0,006<xref ref-type="table-fn" rid="TFN10">*</xref></td>
                  <td align="center">0,917</td>
                </tr>
                <tr>
                  <td align="left">Mulheres</td>
                  <td align="center">6,35</td>
                  <td align="center">9,32</td>
                  <td align="center">8,52</td>
                  <td align="center">9,02</td>
                  <td align="center">10,08</td>
                  <td align="center">10,39</td>
                  <td align="center">11,49</td>
                  <td align="center">13,56</td>
                  <td align="center">12,69</td>
                  <td align="center">11,93</td>
                  <td align="center">0,006<xref ref-type="table-fn" rid="TFN10">*</xref></td>
                  <td align="center">0,908</td>
                </tr>
                <tr>
                  <td align="left">Homens</td>
                  <td align="center">6,76</td>
                  <td align="center">7,67</td>
                  <td align="center">7,36</td>
                  <td align="center">8,15</td>
                  <td align="center">10,20</td>
                  <td align="center">9,12</td>
                  <td align="center">11,02</td>
                  <td align="center">10,61</td>
                  <td align="center">11,59</td>
                  <td align="center">9,40</td>
                  <td align="center">0,013<xref ref-type="table-fn" rid="TFN10">*</xref></td>
                  <td align="center">0,828</td>
                </tr>
                <tr>
                  <td align="left">N&#250;mero de admiss&#245;es</td>
                  <td align="center">7143</td>
                  <td align="center">6890</td>
                  <td align="center">7331</td>
                  <td align="center">6571</td>
                  <td align="center">5450</td>
                  <td align="center">4739</td>
                  <td align="center">4102</td>
                  <td align="center">3112</td>
                  <td align="center">3115</td>
                  <td align="center">2719</td>
                  <td align="center">0,004<xref ref-type="table-fn" rid="TFN10">*</xref></td>
                  <td align="center">-0,970</td>
                </tr>
                <tr>
                  <td align="left">
                    <bold>Mortes por faixa et&#225;ria (popula&#231;&#227;o)</bold>
                  </td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                </tr>
                <tr>
                  <td align="left">15-19 anos</td>
                  <td align="center">2</td>
                  <td align="center">2</td>
                  <td align="center">3</td>
                  <td align="center">2</td>
                  <td align="center">1</td>
                  <td align="center">0</td>
                  <td align="center">1</td>
                  <td align="center">1</td>
                  <td align="center">------</td>
                  <td align="center">------</td>
                  <td align="center">0,067</td>
                  <td align="center">-0,693</td>
                </tr>
                <tr>
                  <td align="left">20-29 anos</td>
                  <td align="center">3</td>
                  <td align="center">8</td>
                  <td align="center">8</td>
                  <td align="center">5</td>
                  <td align="center">5</td>
                  <td align="center">6</td>
                  <td align="center">2</td>
                  <td align="center">6</td>
                  <td align="center">------</td>
                  <td align="center">------</td>
                  <td align="center">0,588</td>
                  <td align="center">-0,205</td>
                </tr>
                <tr>
                  <td align="left">30-39 anos</td>
                  <td align="center">8</td>
                  <td align="center">16</td>
                  <td align="center">9</td>
                  <td align="center">13</td>
                  <td align="center">9</td>
                  <td align="center">10</td>
                  <td align="center">10</td>
                  <td align="center">8</td>
                  <td align="center">------</td>
                  <td align="center">------</td>
                  <td align="center">0,389</td>
                  <td align="center">-0,326</td>
                </tr>
                <tr>
                  <td align="left">40-49 anos</td>
                  <td align="center">21</td>
                  <td align="center">22</td>
                  <td align="center">29</td>
                  <td align="center">23</td>
                  <td align="center">25</td>
                  <td align="center">23</td>
                  <td align="center">24</td>
                  <td align="center">13</td>
                  <td align="center">------</td>
                  <td align="center">------</td>
                  <td align="center">0,292</td>
                  <td align="center">-0,399</td>
                </tr>
                <tr>
                  <td align="left">50-59 anos</td>
                  <td align="center">47</td>
                  <td align="center">42</td>
                  <td align="center">53</td>
                  <td align="center">33</td>
                  <td align="center">45</td>
                  <td align="center">48</td>
                  <td align="center">46</td>
                  <td align="center">36</td>
                  <td align="center">------</td>
                  <td align="center">------</td>
                  <td align="center">0,479</td>
                  <td align="center">-0,267</td>
                </tr>
                <tr>
                  <td align="left">60-69 anos</td>
                  <td align="center">84</td>
                  <td align="center">88</td>
                  <td align="center">92</td>
                  <td align="center">75</td>
                  <td align="center">92</td>
                  <td align="center">101</td>
                  <td align="center">82</td>
                  <td align="center">93</td>
                  <td align="center">------</td>
                  <td align="center">------</td>
                  <td align="center">0,457</td>
                  <td align="center">0,281</td>
                </tr>
                <tr>
                  <td align="left">70-79 anos</td>
                  <td align="center">164</td>
                  <td align="center">172</td>
                  <td align="center">152</td>
                  <td align="center">172</td>
                  <td align="center">147</td>
                  <td align="center">179</td>
                  <td align="center">174</td>
                  <td align="center">154</td>
                  <td align="center">------</td>
                  <td align="center">------</td>
                  <td align="center">0,979</td>
                  <td align="center">-0,010</td>
                </tr>
                <tr>
                  <td align="left">Mais de 80 anos</td>
                  <td align="center">387</td>
                  <td align="center">422</td>
                  <td align="center">423</td>
                  <td align="center">427</td>
                  <td align="center">394</td>
                  <td align="center">401</td>
                  <td align="center">385</td>
                  <td align="center">372</td>
                  <td align="center">------</td>
                  <td align="center">------</td>
                  <td align="center">0,143</td>
                  <td align="center">-0,553</td>
                </tr>
                <tr>
                  <td align="left">
                    <bold>&#211;bitos por faixa et&#225;ria (no hospital)</bold>
                  </td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                </tr>
                <tr>
                  <td align="left">15-19 anos</td>
                  <td align="center">3</td>
                  <td align="center">2</td>
                  <td align="center">3</td>
                  <td align="center">3</td>
                  <td align="center">2</td>
                  <td align="center">2</td>
                  <td align="center">2</td>
                  <td align="center">2</td>
                  <td align="center">4</td>
                  <td align="center">2</td>
                  <td align="center">0,815</td>
                  <td align="center">-0,078</td>
                </tr>
                <tr>
                  <td align="left">20-29 anos</td>
                  <td align="center">11</td>
                  <td align="center">10</td>
                  <td align="center">8</td>
                  <td align="center">5</td>
                  <td align="center">5</td>
                  <td align="center">4</td>
                  <td align="center">4</td>
                  <td align="center">7</td>
                  <td align="center">2</td>
                  <td align="center">2</td>
                  <td align="center">0,010<xref ref-type="table-fn" rid="TFN10">*</xref></td>
                  <td align="center">-0,859</td>
                </tr>
                <tr>
                  <td align="left">30-39 anos</td>
                  <td align="center">17</td>
                  <td align="center">19</td>
                  <td align="center">16</td>
                  <td align="center">11</td>
                  <td align="center">16</td>
                  <td align="center">12</td>
                  <td align="center">7</td>
                  <td align="center">8</td>
                  <td align="center">6</td>
                  <td align="center">8</td>
                  <td align="center">0,008<xref ref-type="table-fn" rid="TFN10">*</xref></td>
                  <td align="center">-0,887</td>
                </tr>
                <tr>
                  <td align="left">40-49 anos</td>
                  <td align="center">24</td>
                  <td align="center">35</td>
                  <td align="center">35</td>
                  <td align="center">35</td>
                  <td align="center">36</td>
                  <td align="center">30</td>
                  <td align="center">19</td>
                  <td align="center">10</td>
                  <td align="center">10</td>
                  <td align="center">17</td>
                  <td align="center">0,029<xref ref-type="table-fn" rid="TFN10">*</xref></td>
                  <td align="center">-0,727</td>
                </tr>
                <tr>
                  <td align="left">50-59 anos</td>
                  <td align="center">55</td>
                  <td align="center">53</td>
                  <td align="center">53</td>
                  <td align="center">55</td>
                  <td align="center">63</td>
                  <td align="center">47</td>
                  <td align="center">46</td>
                  <td align="center">24</td>
                  <td align="center">38</td>
                  <td align="center">35</td>
                  <td align="center">0,025<xref ref-type="table-fn" rid="TFN10">*</xref></td>
                  <td align="center">-0,748</td>
                </tr>
                <tr>
                  <td align="left">60-69 anos</td>
                  <td align="center">77</td>
                  <td align="center">97</td>
                  <td align="center">96</td>
                  <td align="center">97</td>
                  <td align="center">101</td>
                  <td align="center">86</td>
                  <td align="center">93</td>
                  <td align="center">72</td>
                  <td align="center">76</td>
                  <td align="center">44</td>
                  <td align="center">0,061</td>
                  <td align="center">-0,625</td>
                </tr>
                <tr>
                  <td align="left">70-79 anos</td>
                  <td align="center">129</td>
                  <td align="center">150</td>
                  <td align="center">136</td>
                  <td align="center">142</td>
                  <td align="center">131</td>
                  <td align="center">119</td>
                  <td align="center">129</td>
                  <td align="center">96</td>
                  <td align="center">89</td>
                  <td align="center">75</td>
                  <td align="center">0,009<xref ref-type="table-fn" rid="TFN10">*</xref></td>
                  <td align="center">-0,865</td>
                </tr>
                <tr>
                  <td align="left">Mais de 80 anos</td>
                  <td align="center">149</td>
                  <td align="center">213</td>
                  <td align="center">227</td>
                  <td align="center">211</td>
                  <td align="center">194</td>
                  <td align="center">157</td>
                  <td align="center">156</td>
                  <td align="center">153</td>
                  <td align="center">148</td>
                  <td align="center">129</td>
                  <td align="center">0,052</td>
                  <td align="center">-0,649</td>
                </tr>
                <tr>
                  <td align="left">Tempo m&#233;dio de interna&#231;&#227;o (dias)</td>
                  <td align="center">5</td>
                  <td align="center">5,2</td>
                  <td align="center">5,3</td>
                  <td align="center">5,5</td>
                  <td align="center">5,6</td>
                  <td align="center">5,6</td>
                  <td align="center">6,1</td>
                  <td align="center">6,5</td>
                  <td align="center">7,2</td>
                  <td align="center">7,2</td>
                  <td align="center">0,004<xref ref-type="table-fn" rid="TFN10">*</xref></td>
                  <td align="center">0,953</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN10">
                <label>*</label>
                <p>p &lt; 0,05;</p>
              </fn>
              <fn id="TFN11">
                <label>&#8224;</label>
                <p>Valor de P para tend&#234;ncias de acordo com teste de tend&#234;ncia linear de Mantel Haenzel;</p>
              </fn>
              <attrib>Fonte dos dados: Sistema de Informa&#231;&#227;o do SUS (DATASUS) e Instituto Brasileiro de Geografia e Estat&#237;stica (contagem de 2010).</attrib>
            </table-wrap-foot>
          </table-wrap>
          <table-wrap id="t7">
            <label>Tabela 3</label>
            <caption>
              <title>Tend&#234;ncias da insufici&#234;ncia card&#237;aca no Brasil, de 2008 a 2017</title>
            </caption>
            <table frame="hsides" rules="groups">
              <colgroup>
                <col width="7%"/>
                <col width="7%"/>
                <col width="7%"/>
                <col width="7%"/>
                <col width="7%"/>
                <col width="7%"/>
                <col width="7%"/>
                <col width="7%"/>
                <col width="7%"/>
                <col width="7%"/>
                <col width="7%"/>
                <col width="7%"/>
                <col width="7%"/>
              </colgroup>
              <thead>
                <tr>
                  <th align="left">Vari&#225;veis</th>
                  <th align="center">2008</th>
                  <th align="center">2009</th>
                  <th align="center">2010</th>
                  <th align="center">2011</th>
                  <th align="center">2012</th>
                  <th align="center">2013</th>
                  <th align="center">2014</th>
                  <th align="center">2015</th>
                  <th align="center">2016</th>
                  <th align="center">2017</th>
                  <th align="center">Valores P para tend&#234;ncias<xref ref-type="table-fn" rid="TFN12">*</xref><xref ref-type="table-fn" rid="TFN13">&#8224;</xref></th>
                  <th align="center">Pearson (R)</th>
                </tr>
              </thead>
              <tbody>
                <tr>
                  <td align="left">N&#250;mero de mortes (popula&#231;&#227;o)</td>
                  <td align="center">27.567</td>
                  <td align="center">27.314</td>
                  <td align="center">27.544</td>
                  <td align="center">27.818</td>
                  <td align="center">26.694</td>
                  <td align="center">27.290</td>
                  <td align="center">26.783</td>
                  <td align="center">27.434</td>
                  <td align="center">------</td>
                  <td align="center">------</td>
                  <td align="center">0,276</td>
                  <td align="center">-0,412</td>
                </tr>
                <tr>
                  <td align="left">Mulheres</td>
                  <td align="center">13.990</td>
                  <td align="center">14.136</td>
                  <td align="center">14.236</td>
                  <td align="center">14.525</td>
                  <td align="center">13.824</td>
                  <td align="center">14.014</td>
                  <td align="center">13.846</td>
                  <td align="center">14.435</td>
                  <td align="center">------</td>
                  <td align="center">------</td>
                  <td align="center">0,929</td>
                  <td align="center">0,034</td>
                </tr>
                <tr>
                  <td align="left">Homens</td>
                  <td align="center">13.428</td>
                  <td align="center">13.047</td>
                  <td align="center">13.159</td>
                  <td align="center">13.130</td>
                  <td align="center">12.756</td>
                  <td align="center">13.166</td>
                  <td align="center">12.825</td>
                  <td align="center">12.900</td>
                  <td align="center">------</td>
                  <td align="center">------</td>
                  <td align="center">0,069</td>
                  <td align="center">-0,689</td>
                </tr>
                <tr>
                  <td align="left">N&#250;mero de &#243;bitos (no hospital)</td>
                  <td align="center">22.513</td>
                  <td align="center">23.043</td>
                  <td align="center">23.667</td>
                  <td align="center">24.451</td>
                  <td align="center">23.071</td>
                  <td align="center">22.858</td>
                  <td align="center">22.031</td>
                  <td align="center">22.756</td>
                  <td align="center">23,519</td>
                  <td align="center">19,209</td>
                  <td align="center">0,131</td>
                  <td align="center">-0,504</td>
                </tr>
                <tr>
                  <td align="left">Mulheres</td>
                  <td align="center">11.021</td>
                  <td align="center">11.356</td>
                  <td align="center">11.740</td>
                  <td align="center">12.099</td>
                  <td align="center">11.426</td>
                  <td align="center">11.305</td>
                  <td align="center">10.963</td>
                  <td align="center">11.450</td>
                  <td align="center">11,738</td>
                  <td align="center">10,509</td>
                  <td align="center">0,401</td>
                  <td align="center">-0,280</td>
                </tr>
                <tr>
                  <td align="left">Homens</td>
                  <td align="center">11.198</td>
                  <td align="center">11.395</td>
                  <td align="center">11.676</td>
                  <td align="center">12.092</td>
                  <td align="center">11.408</td>
                  <td align="center">11.301</td>
                  <td align="center">10.823</td>
                  <td align="center">11.097</td>
                  <td align="center">11,577</td>
                  <td align="center">10,213</td>
                  <td align="center">0,119</td>
                  <td align="center">-0,520</td>
                </tr>
                <tr>
                  <td align="left">Taxa de mortalidade (popula&#231;&#227;o)</td>
                  <td align="center">14,54</td>
                  <td align="center">14,26</td>
                  <td align="center">14,44</td>
                  <td align="center">14,46</td>
                  <td align="center">13,76</td>
                  <td align="center">13,57</td>
                  <td align="center">13,21</td>
                  <td align="center">13,42</td>
                  <td align="center">------</td>
                  <td align="center">------</td>
                  <td align="center">0,017<xref ref-type="table-fn" rid="TFN12">*</xref></td>
                  <td align="center">-0,905</td>
                </tr>
                <tr>
                  <td align="left">Taxa de mortalidade (intra-hospitalar)</td>
                  <td align="center">8,3</td>
                  <td align="center">8,5</td>
                  <td align="center">8,9</td>
                  <td align="center">9,4</td>
                  <td align="center">9,5</td>
                  <td align="center">9,7</td>
                  <td align="center">9,8</td>
                  <td align="center">10,5</td>
                  <td align="center">11,0</td>
                  <td align="center">10,8</td>
                  <td align="center">0,003<xref ref-type="table-fn" rid="TFN12">*</xref></td>
                  <td align="center">0,981</td>
                </tr>
                <tr>
                  <td align="left">Mulheres</td>
                  <td align="center">8,5</td>
                  <td align="center">8,7</td>
                  <td align="center">9,2</td>
                  <td align="center">9,6</td>
                  <td align="center">9,8</td>
                  <td align="center">10,0</td>
                  <td align="center">10,2</td>
                  <td align="center">11,0</td>
                  <td align="center">11,5</td>
                  <td align="center">11,2</td>
                  <td align="center">0,003<xref ref-type="table-fn" rid="TFN12">*</xref></td>
                  <td align="center">0,980</td>
                </tr>
                <tr>
                  <td align="left">Homens</td>
                  <td align="center">8,2</td>
                  <td align="center">8,4</td>
                  <td align="center">8,7</td>
                  <td align="center">9,2</td>
                  <td align="center">9,3</td>
                  <td align="center">9,4</td>
                  <td align="center">9,6</td>
                  <td align="center">10,1</td>
                  <td align="center">10,6</td>
                  <td align="center">10,4</td>
                  <td align="center">0,003<xref ref-type="table-fn" rid="TFN12">*</xref></td>
                  <td align="center">0,985</td>
                </tr>
                <tr>
                  <td align="left">N&#250;mero de admiss&#245;es</td>
                  <td align="center">270.988</td>
                  <td align="center">269.891</td>
                  <td align="center">265.038</td>
                  <td align="center">260.995</td>
                  <td align="center">242.919</td>
                  <td align="center">236.550</td>
                  <td align="center">223.825</td>
                  <td align="center">217.050</td>
                  <td align="center">214,432</td>
                  <td align="center">178,445</td>
                  <td align="center">0,004<xref ref-type="table-fn" rid="TFN12">*</xref></td>
                  <td align="center">-0,964</td>
                </tr>
                <tr>
                  <td align="left">
                    <bold>Mortes por faixa et&#225;ria (popula&#231;&#227;o)</bold>
                  </td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                </tr>
                <tr>
                  <td align="left">15-19 anos</td>
                  <td align="center">56</td>
                  <td align="center">55</td>
                  <td align="center">47</td>
                  <td align="center">49</td>
                  <td align="center">51</td>
                  <td align="center">41</td>
                  <td align="center">40</td>
                  <td align="center">35</td>
                  <td align="center">------</td>
                  <td align="center">------</td>
                  <td align="center">0,014<xref ref-type="table-fn" rid="TFN12">*</xref></td>
                  <td align="center">-0,926</td>
                </tr>
                <tr>
                  <td align="left">20-29 anos</td>
                  <td align="center">206</td>
                  <td align="center">204</td>
                  <td align="center">180</td>
                  <td align="center">176</td>
                  <td align="center">165</td>
                  <td align="center">174</td>
                  <td align="center">159</td>
                  <td align="center">145</td>
                  <td align="center">------</td>
                  <td align="center">------</td>
                  <td align="center">0,012<xref ref-type="table-fn" rid="TFN12">*</xref></td>
                  <td align="center">-0,947</td>
                </tr>
                <tr>
                  <td align="left">30-39 anos</td>
                  <td align="center">468</td>
                  <td align="center">415</td>
                  <td align="center">379</td>
                  <td align="center">387</td>
                  <td align="center">396</td>
                  <td align="center">373</td>
                  <td align="center">358</td>
                  <td align="center">355</td>
                  <td align="center">------</td>
                  <td align="center">------</td>
                  <td align="center">0,022<xref ref-type="table-fn" rid="TFN12">*</xref></td>
                  <td align="center">-0,863</td>
                </tr>
                <tr>
                  <td align="left">40-49 anos</td>
                  <td align="center">1.039</td>
                  <td align="center">1.002</td>
                  <td align="center">1.034</td>
                  <td align="center">957</td>
                  <td align="center">913</td>
                  <td align="center">920</td>
                  <td align="center">836</td>
                  <td align="center">815</td>
                  <td align="center">------</td>
                  <td align="center">------</td>
                  <td align="center">0,011<xref ref-type="table-fn" rid="TFN12">*</xref></td>
                  <td align="center">-0,957</td>
                </tr>
                <tr>
                  <td align="left">50-59 anos</td>
                  <td align="center">2.389</td>
                  <td align="center">2.303</td>
                  <td align="center">2.293</td>
                  <td align="center">2.269</td>
                  <td align="center">2.259</td>
                  <td align="center">2.214</td>
                  <td align="center">2.072</td>
                  <td align="center">2.157</td>
                  <td align="center">------</td>
                  <td align="center">------</td>
                  <td align="center">0,016<xref ref-type="table-fn" rid="TFN12">*</xref></td>
                  <td align="center">-0,910</td>
                </tr>
                <tr>
                  <td align="left">60-69 anos</td>
                  <td align="center">4.296</td>
                  <td align="center">4.249</td>
                  <td align="center">4.196</td>
                  <td align="center">4.268</td>
                  <td align="center">4.057</td>
                  <td align="center">4.230</td>
                  <td align="center">4.123</td>
                  <td align="center">4.255</td>
                  <td align="center">------</td>
                  <td align="center">------</td>
                  <td align="center">0,328</td>
                  <td align="center">-0,370</td>
                </tr>
                <tr>
                  <td align="left">70-79 anos</td>
                  <td align="center">7.178</td>
                  <td align="center">7.027</td>
                  <td align="center">7.062</td>
                  <td align="center">7.013</td>
                  <td align="center">6.727</td>
                  <td align="center">6.969</td>
                  <td align="center">6.707</td>
                  <td align="center">6.845</td>
                  <td align="center">------</td>
                  <td align="center">------</td>
                  <td align="center">0,037<xref ref-type="table-fn" rid="TFN12">*</xref></td>
                  <td align="center">-0,788</td>
                </tr>
                <tr>
                  <td align="left">Mais de 80 anos</td>
                  <td align="center">11.788</td>
                  <td align="center">11.928</td>
                  <td align="center">12.206</td>
                  <td align="center">12.539</td>
                  <td align="center">12.012</td>
                  <td align="center">12.259</td>
                  <td align="center">12.383</td>
                  <td align="center">12.733</td>
                  <td align="center">------</td>
                  <td align="center">------</td>
                  <td align="center">0,039<xref ref-type="table-fn" rid="TFN12">*</xref></td>
                  <td align="center">0,782</td>
                </tr>
                <tr>
                  <td align="left">
                    <bold>&#211;bitos por faixa et&#225;ria (no hospital)</bold>
                  </td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                  <td align="center">&#160;</td>
                </tr>
                <tr>
                  <td align="left">15-19 anos</td>
                  <td align="center">87</td>
                  <td align="center">97</td>
                  <td align="center">75</td>
                  <td align="center">73</td>
                  <td align="center">61</td>
                  <td align="center">65</td>
                  <td align="center">59</td>
                  <td align="center">61</td>
                  <td align="center">61</td>
                  <td align="center">38</td>
                  <td align="center">0,007<xref ref-type="table-fn" rid="TFN12">*</xref></td>
                  <td align="center">-0,898</td>
                </tr>
                <tr>
                  <td align="left">20-29 anos</td>
                  <td align="center">284</td>
                  <td align="center">271</td>
                  <td align="center">264</td>
                  <td align="center">241</td>
                  <td align="center">220</td>
                  <td align="center">230</td>
                  <td align="center">188</td>
                  <td align="center">176</td>
                  <td align="center">175</td>
                  <td align="center">152</td>
                  <td align="center">0,003<xref ref-type="table-fn" rid="TFN12">*</xref></td>
                  <td align="center">-0,984</td>
                </tr>
                <tr>
                  <td align="left">30-39 anos</td>
                  <td align="center">597</td>
                  <td align="center">529</td>
                  <td align="center">503</td>
                  <td align="center">501</td>
                  <td align="center">475</td>
                  <td align="center">451</td>
                  <td align="center">445</td>
                  <td align="center">437</td>
                  <td align="center">434</td>
                  <td align="center">369</td>
                  <td align="center">0,008<xref ref-type="table-fn" rid="TFN12">*</xref></td>
                  <td align="center">-0,887</td>
                </tr>
                <tr>
                  <td align="left">40-49 anos</td>
                  <td align="center">1.278</td>
                  <td align="center">1.216</td>
                  <td align="center">1.227</td>
                  <td align="center">1.216</td>
                  <td align="center">1.104</td>
                  <td align="center">1.102</td>
                  <td align="center">981</td>
                  <td align="center">1.004</td>
                  <td align="center">1,052</td>
                  <td align="center">853</td>
                  <td align="center">0,005<xref ref-type="table-fn" rid="TFN12">*</xref></td>
                  <td align="center">-0,931</td>
                </tr>
                <tr>
                  <td align="left">50-59 anos</td>
                  <td align="center">2.687</td>
                  <td align="center">2.722</td>
                  <td align="center">2.736</td>
                  <td align="center">2.793</td>
                  <td align="center">2.700</td>
                  <td align="center">2.620</td>
                  <td align="center">2.372</td>
                  <td align="center">2.498</td>
                  <td align="center">2,569</td>
                  <td align="center">2,149</td>
                  <td align="center">0,019<xref ref-type="table-fn" rid="TFN12">*</xref></td>
                  <td align="center">-0,783</td>
                </tr>
                <tr>
                  <td align="left">60-69 anos</td>
                  <td align="center">4.358</td>
                  <td align="center">4.578</td>
                  <td align="center">4.739</td>
                  <td align="center">4.769</td>
                  <td align="center">4.599</td>
                  <td align="center">4.452</td>
                  <td align="center">4.439</td>
                  <td align="center">4.601</td>
                  <td align="center">4,783</td>
                  <td align="center">4,149</td>
                  <td align="center">0,533</td>
                  <td align="center">-0,208</td>
                </tr>
                <tr>
                  <td align="left">70-79 anos</td>
                  <td align="center">6.337</td>
                  <td align="center">6.371</td>
                  <td align="center">6.583</td>
                  <td align="center">6.820</td>
                  <td align="center">6.237</td>
                  <td align="center">6.343</td>
                  <td align="center">5.984</td>
                  <td align="center">6.174</td>
                  <td align="center">6,496</td>
                  <td align="center">5,706</td>
                  <td align="center">0,101</td>
                  <td align="center">-0,546</td>
                </tr>
                <tr>
                  <td align="left">Mais de 80 anos</td>
                  <td align="center">6.591</td>
                  <td align="center">6.967</td>
                  <td align="center">7.289</td>
                  <td align="center">7.778</td>
                  <td align="center">7.438</td>
                  <td align="center">7.343</td>
                  <td align="center">7.318</td>
                  <td align="center">7.596</td>
                  <td align="center">7,745</td>
                  <td align="center">7,306</td>
                  <td align="center">0,064</td>
                  <td align="center">0,617</td>
                </tr>
                <tr>
                  <td align="left">Tempo m&#233;dio de interna&#231;&#227;o (dias)</td>
                  <td align="center">6,5</td>
                  <td align="center">6,4</td>
                  <td align="center">6,5</td>
                  <td align="center">6,6</td>
                  <td align="center">6,7</td>
                  <td align="center">6,9</td>
                  <td align="center">7,1</td>
                  <td align="center">7,3</td>
                  <td align="center">7,4</td>
                  <td align="center">7,3</td>
                  <td align="center">0,004<xref ref-type="table-fn" rid="TFN12">*</xref></td>
                  <td align="center">0,960</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN12">
                <label>*</label>
                <p>p &lt; 0,05;</p>
              </fn>
              <fn id="TFN13">
                <label>&#8224;</label>
                <p>Valor de P para tend&#234;ncias de acordo com o teste de tend&#234;ncia linear de Mantel Haenzel;</p>
              </fn>
              <attrib>Fonte dos dados: Sistema de Informa&#231;&#227;o do SUS (DATASUS) e Instituto Brasileiro de Geografia e Estat&#237;stica (contagem de 2010).</attrib>
            </table-wrap-foot>
          </table-wrap>
          <p>
            <fig id="f7">
              <label>Figura 1</label>
              <caption>
                <title>Tend&#234;ncia do n&#250;mero (absoluto) de interna&#231;&#245;es por insufici&#234;ncia card&#237;aca de 2008 a 2017 na Para&#237;ba (A) e regi&#245;es do Brasil (B).</title>
              </caption>
              <graphic xlink:href="1678-4170-abc-114-02-0222-80321-gf01-pt.tif"/></fig>
          </p>
          <p>Quando estratificados por idade, os indiv&#237;duos com idade superior a 60 anos corresponderam a 71% e 73% de todos os casos de interna&#231;&#227;o por IC na Para&#237;ba e no Brasil, respectivamente, com o maior n&#250;mero na faixa de idade entre 70 e 79 anos.</p>
        </sec>
        <sec>
          <title>Mortalidade absoluta da popula&#231;&#227;o</title>
          <p>A mortalidade por IC em n&#250;meros absolutos da popula&#231;&#227;o apresentou um decl&#237;nio n&#227;o significativo de 2008 a 2015 na Para&#237;ba (R = -0,513; p = 0,175; <xref ref-type="table" rid="t6">Tabela 2</xref>) e Brasil (R = -0,412; p = 0,276; <xref ref-type="table" rid="t7">Tabela 3</xref>), sem diferen&#231;a quanto ao g&#234;nero. As mulheres representaram 53% dos &#243;bitos na Para&#237;ba e 52% no Brasil. Na Para&#237;ba, a diminui&#231;&#227;o no n&#250;mero absoluto de mortes por IC na popula&#231;&#227;o em todas as faixas et&#225;rias n&#227;o foi estatisticamente significativa (<xref ref-type="table" rid="t6">Tabela 2</xref>).</p>
          <p>Entre 2008 e 2015, a maior propor&#231;&#227;o de mortes por IC ocorreu na faixa et&#225;ria &#8805; 80 anos tanto em homens como em mulheres na Para&#237;ba (50% e 59%, respectivamente) e no Brasil (38% e 52%, respectivamente). As propor&#231;&#245;es de mortes por IC em indiv&#237;duos com idade &#8805; 60 anos na Para&#237;ba foi 87% nos homens e 90% nas mulheres, e no Brasil 83% nos homens e 89% nas mulheres.</p>
        </sec>
        <sec>
          <title>Taxa de mortalidade da popula&#231;&#227;o</title>
          <p>A m&#233;dia da taxa de mortalidade por IC na popula&#231;&#227;o foi de 19,2/100 000 (&#177;1,09) na Para&#237;ba e 14,0/100 000 (&#177;0,53) no Brasil, com um decl&#237;nio significativo de 10,7% (R = -0,751; p = 0,047; <xref ref-type="table" rid="t6">Tabela 2</xref>) na Para&#237;ba e 7,7% (R = -0,905; p = 0,017; <xref ref-type="table" rid="t7">Tabela 3</xref>) no Brasil entre 2008 e 2015, respectivamente (<xref ref-type="fig" rid="f8">Figura 2</xref>).</p>
          <p>
            <fig id="f8">
              <label>Figura 2</label>
              <caption>
                <title>Tend&#234;ncias na taxa de mortalidade da popula&#231;&#227;o (por 100 000 habitantes) por insufici&#234;ncia card&#237;aca na Para&#237;ba (verde) e Brasil (azul) de 2008 a 2015.</title>
              </caption>
              <graphic xlink:href="1678-4170-abc-114-02-0222-80321-gf02-pt.tif"/></fig>
          </p>
        </sec>
        <sec>
          <title>Mortalidade hospitalar em n&#250;meros absolutos</title>
          <p>A mortalidade hospitalar em n&#250;meros absolutos entre 2008 e 2017 apresentou um decr&#233;scimo significativo de 37,5% na Para&#237;ba (R = -0,824; p = 0,013; <xref ref-type="table" rid="t6">Tabela 2</xref>; <xref ref-type="fig" rid="f9">Figura 3B</xref>) e uma diminui&#231;&#227;o n&#227;o significativa de 14,6% no Brasil (R = -0,504; p = 0,131; <xref ref-type="table" rid="t7">Tabela 3</xref>; <xref ref-type="fig" rid="f9">Figura 3B</xref>). Na an&#225;lise estratificada, observou-se uma diminui&#231;&#227;o significativa no n&#250;mero absoluto de mortes hospitalares por IC tanto para homens como para mulheres na Para&#237;ba (R = -0,837; p = 0,012 e R = -0,762; p = 0,022; <xref ref-type="table" rid="t6">Tabela 2</xref>); tal tend&#234;ncia estatisticamente significativa n&#227;o foi observada no Brasil (<xref ref-type="table" rid="t7">Tabela 3</xref>).</p>
          <p>
            <fig id="f9">
              <label>Figura 3</label>
              <caption>
                <title>(A) Tend&#234;ncia da taxa de mortalidade hospitalar na Para&#237;ba (verde) e Brasil (azul) de 2008 a 2017. (B) Tend&#234;ncia da mortalidade hospitalar (n&#250;mero absoluto) por insufici&#234;ncia card&#237;aca (verde) e Brasil (azul) de 2008 a 2017.</title>
              </caption>
              <graphic xlink:href="1678-4170-abc-114-02-0222-80321-gf03-pt.tif"/></fig>
          </p>
          <p>Indiv&#237;duos com idade superior a 80 anos apresentaram a maior propor&#231;&#227;o de morte hospitalar por IC em n&#250;meros absolutos na Para&#237;ba e no Brasil de 2008 a 2017 (37% e 32%, respectivamente) (<xref ref-type="fig" rid="f10">Figura 4</xref>). Na Para&#237;ba, houve uma redu&#231;&#227;o estatisticamente significativa nas mortes hospitalares por IC para as categorias de idade: 20-29 anos (p = 0,010), 30-39 anos (p = 0,008), 40-49 anos (p = 0,029), 50-59 anos (p = 0,025) e 70-79 anos (p = 0,009) (<xref ref-type="table" rid="t6">Tabela 2</xref>).</p>
          <p>
            <fig id="f10">
              <label>Figura 4</label>
              <caption>
                <title>(A) Mortes hospitalares (n&#250;mero absoluto) por insufici&#234;ncia card&#237;aca por faixa et&#225;ria na Para&#237;ba, de 2008 a 2017; (B) Mortes hospitalares (n&#250;mero absoluto) por insufici&#234;ncia card&#237;aca por faixa et&#225;ria no Brasil, de 2008 a 2017.</title>
              </caption>
              <graphic xlink:href="1678-4170-abc-114-02-0222-80321-gf04-pt.tif"/></fig>
          </p>
          <p>Outros dados do n&#250;mero de mortes hospitalares por IC por faixa et&#225;ria no Brasil est&#227;o descritos na <xref ref-type="table" rid="t7">Tabela 3</xref>.</p>
        </sec>
        <sec>
          <title>Taxa de mortalidade hospitalar</title>
          <p>A taxa de mortalidade hospitalar aumentou significativamente em 65,1% na Para&#237;ba (R = 0,917; p = 0,006; <xref ref-type="table" rid="t6">Tabela 2</xref>), de 6,6% em 2008 a 10,9% em 2017, e em 30,1% no Brasil (R = 0,981; p = 0,003; <xref ref-type="table" rid="t7">Tabela 3</xref>), de 8,3% em 2008 a 10,8% em 2017 (<xref ref-type="fig" rid="f9">Figura 3A</xref>). O aumento na taxa de mortalidade hospitalar por IC por sexo tamb&#233;m foi significativo tanto para homens quanto mulheres na Para&#237;ba (R = 0,828; p = 0,013 e R = 0,908; p = 0,006, respectivamente; <xref ref-type="table" rid="t6">Tabela 2</xref>). Tal tend&#234;ncia tamb&#233;m foi observada no Brasil, em uma magnitude similar (R = 0,985; R = 0,980; p = 0,003; <xref ref-type="table" rid="t7">Tabela 3</xref>).</p>
          <p>A taxa de mortalidade hospitalar por IC por faixa et&#225;ria foi maior nos indiv&#237;duos com idade superior a 80 anos, com uma m&#233;dia de 14,7% na Para&#237;ba e 14,5% no Brasil (<xref ref-type="fig" rid="f11">Figura 5</xref>) de 2008 a 2017. Nessa faixa de idade, a taxa de mortalidade hospitalar por IC por sexo na Para&#237;ba foi 12,4% nos homens e 15,2% nas mulheres e, no Brasil, 13,7% nos homens e 14,9% nas mulheres.</p>
          <p>
            <fig id="f11">
              <label>Figura 5</label>
              <caption>
                <title>(A) Tend&#234;ncia da taxa de mortalidade hospitalar por insufici&#234;ncia card&#237;aca na Para&#237;ba, por faixa et&#225;ria, de 2008 a 2017; (B) Tend&#234;ncia da taxa de mortalidade hospitalar por insufici&#234;ncia card&#237;aca por faixa et&#225;ria no Brasil, de 2008 a 2017.</title>
              </caption>
              <graphic xlink:href="1678-4170-abc-114-02-0222-80321-gf05-pt.tif"/></fig>
          </p>
        </sec>
        <sec>
          <title>Dura&#231;&#227;o da interna&#231;&#227;o hospitalar</title>
          <p>O tempo m&#233;dio de interna&#231;&#227;o hospitalar por IC foi de 5,9 dias (&#177;0,8) na Para&#237;ba e 6,9 dias (&#177;0,4) no Brasil, com aumento significativo de 44% (R = 0,953; p = 0,004; <xref ref-type="table" rid="t6">Tabela 2</xref>) e 12,3% (R = 0,960; p = 0,004; <xref ref-type="table" rid="t7">Tabela 3</xref>), respectivamente entre 2008 e 2017 (<xref ref-type="fig" rid="f12">Figura 6</xref>). Na <xref ref-type="table" rid="t8">Tabela 4</xref>, n&#243;s apresentamos a dura&#231;&#227;o da interna&#231;&#227;o por ano, e os custos associados, tanto na Para&#237;ba como no Brasil.</p>
          <p>
            <fig id="f12">
              <label>Figura 6</label>
              <caption>
                <title>Tend&#234;ncia do per&#237;odo m&#233;dio de interna&#231;&#227;o (dias) por insufici&#234;ncia card&#237;aca na Para&#237;ba (verde) e Brasil (azul) de 2008 a 2017.</title>
              </caption>
              <graphic xlink:href="1678-4170-abc-114-02-0222-80321-gf06-pt.tif"/></fig>
          </p>
          <table-wrap id="t8">
            <label>Tabela 4</label>
            <caption>
              <title>Custo total das interna&#231;&#245;es por IC (US $) e tempo de interna&#231;&#227;o por IC (dias) na Para&#237;ba e no Brasil, de 2008 a 2017</title>
            </caption>
            <table frame="hsides" rules="groups">
              <colgroup>
                <col width="20%"/>
                <col width="20%"/>
                <col width="20%"/>
                <col width="20%"/>
                <col width="20%"/>
              </colgroup>
              <thead>
                <tr>
                  <th align="left" style="border-bottom-width:thin;border-bottom-style:solid">&#160;</th>
                  <th align="center" colspan="2" style="border-bottom-width:thin;border-bottom-style:solid">PARA&#205;BA</th>
                  <th align="center" colspan="2" style="border-bottom-width:thin;border-bottom-style:solid">BRASIL</th>
                </tr>
                <tr>
                  <th align="left">Ano</th>
                  <th align="center">Custo total com hospitaliza&#231;&#245;es (US$)</th>
                  <th align="center">Dura&#231;&#227;o da admiss&#227;o (dias)</th>
                  <th align="center">Custo total com hospitaliza&#231;&#245;es (US$)</th>
                  <th align="center">Dura&#231;&#227;o da admiss&#227;o (dias)</th>
                </tr>
              </thead>
              <tbody>
                <tr>
                  <td align="left">2008</td>
                  <td align="center">1.762.825,91</td>
                  <td align="center">5</td>
                  <td align="center">77.940.473,93</td>
                  <td align="center">6,5</td>
                </tr>
                <tr>
                  <td align="left">2009</td>
                  <td align="center">2.286.531,90</td>
                  <td align="center">5,2</td>
                  <td align="center">89.837.575,25</td>
                  <td align="center">6,4</td>
                </tr>
                <tr>
                  <td align="left">2010</td>
                  <td align="center">2.541.429,71</td>
                  <td align="center">5,3</td>
                  <td align="center">92.835.802,31</td>
                  <td align="center">6,5</td>
                </tr>
                <tr>
                  <td align="left">2011</td>
                  <td align="center">2.378.139,40</td>
                  <td align="center">5,5</td>
                  <td align="center">93.939.042,90</td>
                  <td align="center">6,6</td>
                </tr>
                <tr>
                  <td align="left">2012</td>
                  <td align="center">1.939.284,53</td>
                  <td align="center">5,6</td>
                  <td align="center">91.509.632,22</td>
                  <td align="center">6,7</td>
                </tr>
                <tr>
                  <td align="left">2013</td>
                  <td align="center">1.694.005,09</td>
                  <td align="center">5,6</td>
                  <td align="center">93.561.446,18</td>
                  <td align="center">6,9</td>
                </tr>
                <tr>
                  <td align="left">2014</td>
                  <td align="center">1.578.506,24</td>
                  <td align="center">6,1</td>
                  <td align="center">96.199.113,56</td>
                  <td align="center">7,1</td>
                </tr>
                <tr>
                  <td align="left">2015</td>
                  <td align="center">1.233.302,85</td>
                  <td align="center">6,5</td>
                  <td align="center">99.069.494,68</td>
                  <td align="center">7,3</td>
                </tr>
                <tr>
                  <td align="left">2016</td>
                  <td align="center">1.249.580,27</td>
                  <td align="center">7,2</td>
                  <td align="center">102.181.019,88</td>
                  <td align="center">7,4</td>
                </tr>
                <tr>
                  <td align="left">2017</td>
                  <td align="center">1.103.600,05</td>
                  <td align="center">7,2</td>
                  <td align="center">85.390.241,41</td>
                  <td align="center">7,3</td>
                </tr>
                <tr>
                  <td align="left">Total</td>
                  <td align="center">17.767.205,95</td>
                  <td align="center">5,9 &#177; 0,8 (m&#233;dia &#177; DP)</td>
                  <td align="center">922.463.842,32</td>
                  <td align="center">6,9 &#177; 0,4 (m&#233;dia &#177; DP)</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="TFN14">
                <p>DP: desvio padr&#227;o;</p>
              </fn>
              <attrib>Fonte dos dados: Sistema de Informa&#231;&#227;o do SUS (DATASUS) e Instituto Brasileiro de Geografia e Estat&#237;stica (contagem de 2010).</attrib>
            </table-wrap-foot>
          </table-wrap>
        </sec>
      </sec>
      <sec sec-type="discussion">
        <title>Discuss&#227;o</title>
        <p>Em nosso conhecimento, este &#233; o primeiro estudo a descrever as tend&#234;ncias da epidemiologia da IC em uma regi&#227;o subdesenvolvida do Brasil. Informa&#231;&#245;es sobre a incid&#234;ncia, a preval&#234;ncia, a morbidade e a mortalidade da IC na Am&#233;rica Latina e no Caribe s&#227;o heterog&#234;neas e escassas. A maioria dos dados s&#227;o provenientes da Am&#233;rica do Sul (92%), com o Brasil e a Argentina sendo respons&#225;vel por 86% dos estudos.<xref ref-type="bibr" rid="B10">10</xref> No Brasil, a maioria dos dados publicados s&#227;o origin&#225;rios de &#225;reas desenvolvidas, as regi&#245;es sudeste e sul.</p>
        <p>A IC foi a principal causa de interna&#231;&#245;es entre as doen&#231;as cardiovasculares na Para&#237;ba e no Brasil, e correspondeu a 2,54% e 2,25% de todas as interna&#231;&#245;es, respectivamente. De maneira semelhante, nos EUA, a IC foi a causa de mais de um milh&#227;o de interna&#231;&#245;es por ano de 2001 a 2009,<xref ref-type="bibr" rid="B11">11</xref> e representou 1-2% de todas as interna&#231;&#245;es.<xref ref-type="bibr" rid="B3">3</xref></p>
        <p>Fang et al.,<xref ref-type="bibr" rid="B12">12</xref> realizaram um estudo para determinar as tend&#234;ncias na IC nos EUA, utilizando os dados da Pesquisa Nacional sobre Altas Hospitalares (<italic>National Hospital Discharge Survey</italic>) entre 1979 e 2004, e observaram um aumento de 185% no n&#250;mero absoluto de interna&#231;&#245;es por IC (de 409 000 para 1 166 000), e as taxas de interna&#231;&#245;es por IC (por 100 000) aumentou de 219 para 390 no mesmo per&#237;odo. Outros autores, no entanto, relataram que o n&#250;mero de interna&#231;&#245;es por IC como diagn&#243;stico prim&#225;rio tem diminu&#237;do nos EUA entre 1,0% a 4,3% por ano desde 2001.<xref ref-type="bibr" rid="B11">11</xref><sup>,</sup><xref ref-type="bibr" rid="B13">13</xref> Na Am&#233;rica Latina e Caribe, Godoy et al.,<xref ref-type="bibr" rid="B14">14</xref> mostraram um decr&#233;scimo de 32% nas interna&#231;&#245;es por IC entre 1992-1993 e 2008-2009, o que &#233; consistente com os nossos resultados de uma diminui&#231;&#227;o de 34% no n&#250;mero absoluto de interna&#231;&#245;es por IC no Brasil, e 62% na Para&#237;ba. Essa redu&#231;&#227;o pode ser um sinal de melhora no manejo dos fatores de risco para IC,<xref ref-type="bibr" rid="B4">4</xref> de diminui&#231;&#227;o na incid&#234;ncia de doen&#231;a card&#237;aca isqu&#234;mica,<xref ref-type="bibr" rid="B15">15</xref> e melhoria no manejo da IC.<xref ref-type="bibr" rid="B16">16</xref></p>
        <p>As interna&#231;&#245;es por IC na Para&#237;ba e no Brasil foram mais frequentes em indiv&#237;duos com idade entre 70 e 79 anos. Indiv&#237;duos com idade superior a 60 anos representaram 71% e 73% das interna&#231;&#245;es por IC na Para&#237;ba e no Brasil, respectivamente. Tais frequ&#234;ncias foram similares &#224; observada (70%) em estudos pr&#233;vios conduzidos na Am&#233;rica Latina e Caribe, e nos EUA.<xref ref-type="bibr" rid="B2">2</xref><sup>,</sup><xref ref-type="bibr" rid="B4">4</xref> Na Para&#237;ba e no Brasil, a propor&#231;&#227;o de mulheres hospitalizadas por IC foi 48% e 49%, similar a de estudos realizados nos EUA, com 40% a 50% de mulheres.<xref ref-type="bibr" rid="B3">3</xref><sup>,</sup><xref ref-type="bibr" rid="B17">17</xref> Um pequeno estudo realizado em uma comunidade no Brasil relatou que 58% dos pacientes internados com IC eram mulheres.<xref ref-type="bibr" rid="B18">18</xref> Ainda, o I Registro Brasileiro de Insufici&#234;ncia Card&#237;aca (estudo BREATHE)<xref ref-type="bibr" rid="B8">8</xref> descreveu que 60% de um total de 1263 interna&#231;&#245;es por IC em 51 centros no Brasil eram mulheres.</p>
        <p>Em nosso estudo, a taxa de mortalidade por IC encontrada no per&#237;odo entre 2008 e 2015 foi 19,2/100 000 (&#177;1,09) casos na Para&#237;ba e 14,0/100 000 (&#177;0,53) casos no Brasil, com uma redu&#231;&#227;o de 10,7% e 7,7%, respectivamente. Um decr&#233;scimo na taxa de mortalidade por IC tamb&#233;m foi descrita no Brasil e na Argentina: em S&#227;o Paulo, maior cidade do Brasil, ocorreu uma diminui&#231;&#227;o em 29%, de 19,1/100 000 (1992-1993) para 13,6/100 000 (2008-2009);<xref ref-type="bibr" rid="B14">14</xref> na Argentina, um estudo de abrang&#234;ncia nacional mostrou uma redu&#231;&#227;o de 23% na taxa de mortalidade por IC na popula&#231;&#227;o de 1995 a 2005.<xref ref-type="bibr" rid="B10">10</xref><sup>,</sup><xref ref-type="bibr" rid="B19">19</xref> Nos EUA, Go et al.,<xref ref-type="bibr" rid="B20">20</xref> compararam o n&#250;mero de mortes por IC de 1995 a 2010, e encontraram um decr&#233;scimo de 2,8% (287.000 vs. 279.000), o que potencialmente representa uma diminui&#231;&#227;o significativa na taxa de mortalidade, dado o aumento na popula&#231;&#227;o norte americana nesses quinze anos.</p>
        <p>Nosso estudo relata uma taxa m&#233;dia de mortalidade hospitalar por IC na Para&#237;ba de 9,2% entre 2008 e 2017. Um estudo prospectivo realizado em 52 centros de todas as regi&#245;es brasileira, somente com pacientes internados por IC, relatou um total de 12,6% mortes em 1.263 pacientes internados.<xref ref-type="bibr" rid="B8">8</xref> Na Am&#233;rica Latina e Caribe, uma metan&#225;lise de 37 estudos revelou uma mortalidade hospitalar similar de 11,7%.<xref ref-type="bibr" rid="B10">10</xref></p>
        <p>Nosso estudo mostrou um aumento na taxa de mortalidade hospitalar por IC tanto no estado da Para&#237;ba (65%) como no Brasil (30%) entre 2008 e 2017. Godoy et al.,<xref ref-type="bibr" rid="B14">14</xref> entre 1992-1993 e 2008-2009, tamb&#233;m relataram uma diminui&#231;&#227;o de 15% na taxa de mortalidade hospitalar que era de 15% no Brasil. Nos EUA, no entanto, a taxa de mortalidade hospitalar diminuiu de 4,5% em 2001 para 2,9% em 2014 segundo estudo que incluiu pacientes com diagn&#243;stico prim&#225;rio de IC.<xref ref-type="bibr" rid="B13">13</xref> A diminui&#231;&#227;o no n&#250;mero de interna&#231;&#245;es por IC durante o per&#237;odo estudado, tanto na Para&#237;ba como no Brasil, &#233; a raz&#227;o mais prov&#225;vel para o aumento da taxa de mortalidade hospitalar. Outra explica&#231;&#227;o plaus&#237;vel poderia ser o aumento na sobrevida dos pacientes com IC, levando ao aumento no n&#250;mero de pacientes idosos, com IC mais avan&#231;ada e muitas comorbidades, resultando em um risco aumentado de morte durante interna&#231;&#227;o. Ainda, &#233; importante considerar a falta de terapias avan&#231;adas em &#225;reas pouco desenvolvidas, tais como suporte circulat&#243;rio mec&#226;nico e transplante card&#237;aco, o que contribuiria para essa tend&#234;ncia de aumento na taxa de mortalidade por IC na Para&#237;ba, Brasil, e na Am&#233;rica Latina e Caribe.</p>
        <p>Apesar do aumento na taxa de mortalidade hospitalar, a mortalidade hospitalar em n&#250;meros absolutos mostrou um decr&#233;scimo significativo de 37,5% na Para&#237;ba e 14,6% no Brasil para o mesmo per&#237;odo. Nos EUA, Bueno et al.,<xref ref-type="bibr" rid="B21">21</xref> tamb&#233;m observaram uma diminui&#231;&#227;o de 50% da mortalidade hospitalar por IC na popula&#231;&#227;o composta por idosos participantes do programa Medicare entre 1993 e 2008, ao passo que Ni &amp; Xu<xref ref-type="bibr" rid="B22">22</xref> relataram uma diminui&#231;&#227;o em 30%.</p>
        <p>As mulheres representaram 53% e 52% da mortalidade por IC em n&#250;meros absolutos na Para&#237;ba e no Brasil, respectivamente. A mortalidade hospitalar por IC na Para&#237;ba teve uma propor&#231;&#227;o de mulheres semelhante (50,5%). Nos EUA, em 2010, 54,6% de todas as mortes por IC ocorreram em mulheres.<xref ref-type="bibr" rid="B20">20</xref> Hsich et al.,<xref ref-type="bibr" rid="B23">23</xref> n&#227;o observaram diferen&#231;a na mortalidade hospitalar entre mulheres e homens, considerando pacientes com fra&#231;&#227;o de eje&#231;&#227;o reduzida e pacientes com fra&#231;&#227;o de eje&#231;&#227;o preservada.</p>
        <p>Entre 2008 e 2017, a dura&#231;&#227;o m&#233;dia de interna&#231;&#245;es por IC foi de 5.9 (&#177;0.8) dias na Para&#237;ba e 6,8 (0,4) dias no Brasil, com um aumento de 44% e 12,3%, respectivamente. Na Am&#233;rica Latina e Caribe, Bocchi et al.,<xref ref-type="bibr" rid="B2">2</xref><sup>,</sup><xref ref-type="bibr" rid="B24">24</xref> relataram um per&#237;odo m&#233;dio de interna&#231;&#227;o de 5,8 dias entre 1998 e 2012. Ciapponin et al.,<xref ref-type="bibr" rid="B10">10</xref> relataram uma m&#233;dia de 7 dias em 18 estudos, e Godoy et al.,<xref ref-type="bibr" rid="B14">14</xref> encontraram um aumento de 25% no per&#237;odo de interna&#231;&#227;o, de 8,8 (1992-1993) a 11,3 dias (2008-2009) no Brasil. Nos EUA, dois autores relataram uma diminui&#231;&#227;o no per&#237;odo de interna&#231;&#227;o por IC, de 8,8 para 6,3 dias (1993-2008)<xref ref-type="bibr" rid="B21">21</xref> e de 6,8 (1999-2000) para 6,4 dias (2007-2008).<xref ref-type="bibr" rid="B4">4</xref></p>
        <p>Nos EUA, o custo per capita em sa&#250;de foi maior que o produto interno bruto per capita na Para&#237;ba (US$8364,00 e US$3594,94, respectivamente).<xref ref-type="bibr" rid="B24">24</xref> O status socioecon&#244;mico mais baixo na Para&#237;ba pode representar um fator de risco para maior morbidade e mortalidade observada em nosso estudo, j&#225; que a popula&#231;&#227;o tem acesso limitado a tratamento efetivo para IC.<xref ref-type="bibr" rid="B24">24</xref> Nos EUA, 52,5% da popula&#231;&#227;o com renda familiar menor que 10 000 d&#243;lares apresentam doen&#231;a cardiovascular,<xref ref-type="bibr" rid="B20">20</xref><sup>,</sup><xref ref-type="bibr" rid="B25">25</xref> e Eapen et al.<xref ref-type="bibr" rid="B26">26</xref> identificaram que uma maior renda associou-se com menor chance de mortalidade 30 dias ap&#243;s interna&#231;&#227;o por IC.</p>
        <sec>
          <title>Limita&#231;&#245;es</title>
          <p>Este &#233; um estudo observacional retrospectivo, e a aus&#234;ncia de dados individuais dos pacientes impediu o estabelecimento de rela&#231;&#245;es entre as vari&#225;veis. Uma vez que nossos dados foram derivados de um banco de dados nacional, &#233; poss&#237;vel que haja ocorrido subnotifica&#231;&#227;o ou notifica&#231;&#227;o err&#244;nea dos dados. Ainda, uma vez que reinterna&#231;&#245;es n&#227;o s&#227;o consideradas no n&#250;mero total de interna&#231;&#245;es por IC, a taxa de mortalidade hospitalar pode ter sido subestimada.</p>
        </sec>
      </sec>
      <sec sec-type="conclusions">
        <title>Conclus&#245;es</title>
        <p>Este &#233; o primeiro estudo a analisar a epidemiologia da IC na Para&#237;ba, um estado de baixo status socioecon&#244;mico no Brasil, e a comparar os resultados com dados nacionais e internacionais. Durante os &#250;ltimos dez anos, o aumento na taxa de mortalidade hospitalar por IC na Para&#237;ba e no Brasil acompanhou a tend&#234;ncia na Am&#233;rica Latina e Caribe, enquanto o aumento na dura&#231;&#227;o da interna&#231;&#227;o por IC difere da diminui&#231;&#227;o observada nos EUA. Na Para&#237;ba e no Brasil, observamos uma diminui&#231;&#227;o nas interna&#231;&#245;es por IC como diagn&#243;stico prim&#225;rio bem como no n&#250;mero de mortes por IC, o que tamb&#233;m foi descrito na Am&#233;rica Latina, Caribe e nos EUA. Mais de 87% das mortes por IC na Para&#237;ba e no Brasil envolveram pacientes com mais de 60 anos de idade. Observou-se uma maior frequ&#234;ncia de mulheres admitidas por IC, na Para&#237;ba e no Brasil, com taxas de mortalidades similares em compara&#231;&#227;o a homens. Uma vez que as mulheres s&#227;o geralmente pouco representadas nos ensaios cl&#237;nicos, h&#225; necessidade de mais estudos com foco nessa popula&#231;&#227;o. Deveriam ser realizados estudos cl&#237;nicos em hospitais para identificar as causas para a tend&#234;ncia do aumento da taxa de mortalidade hospitalar por IC.</p>
      </sec>
    </body>
    <back>
      <fn-group>
        <fn fn-type="financial-disclosure">
          <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 deste estudo a programas de p&#243;s-gradua&#231;&#227;o.</p>
        </fn>
        <fn fn-type="other">
          <p>
            <bold>Aprova&#231;&#227;o &#233;tica e consentimento informado</bold>
          </p>
          <p>Este artigo n&#227;o cont&#233;m estudos com humanos ou animais realizados por nenhum dos autores.</p>
        </fn>
      </fn-group>
    </back>
  </sub-article>
</article>
