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  <front>
    <journal-meta>
      <journal-id journal-id-type="nlm-ta">Arq Bras Cardiol</journal-id>
      <journal-id journal-id-type="publisher-id">abc</journal-id>
      <journal-title-group>
        <journal-title>Arquivos Brasileiros de Cardiologia</journal-title>
        <abbrev-journal-title abbrev-type="publisher">Arq. Bras. Cardiol.</abbrev-journal-title>
      </journal-title-group>
      <issn pub-type="ppub">0066-782X</issn>
      <issn pub-type="epub">1678-4170</issn>
      <publisher>
        <publisher-name>Sociedade Brasileira de Cardiologia - SBC</publisher-name>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v3">v7MFYCy5tRQkmJhw74psbQL</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v2">S0066-782X2015002500580</article-id>
      <article-id pub-id-type="publisher-id" specific-use="previous-pid">S0066-782X2015005050125</article-id>
      <article-id pub-id-type="doi">10.5935/abc.20150125</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Original Articles</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Cardiovascular Autonomic Dysfunction in Patients with Morbid Obesity</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Sant Anna</surname>
            <given-names>Maur&#237;cio de</given-names>
            <suffix>Junior</suffix>
          </name>
          <xref ref-type="aff" rid="aff01">1</xref>
          <xref ref-type="aff" rid="aff02">2</xref>
          <xref ref-type="aff" rid="aff05">5</xref>
          <xref ref-type="aff" rid="aff06">6</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Carneiro</surname>
            <given-names>Jo&#227;o Regis Ivar</given-names>
          </name>
          <xref ref-type="aff" rid="aff01">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Carvalhal</surname>
            <given-names>Renata Ferreira</given-names>
          </name>
          <xref ref-type="aff" rid="aff01">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Torres</surname>
            <given-names>Diego de Faria Magalh&#227;es</given-names>
          </name>
          <xref ref-type="aff" rid="aff01">1</xref>
          <xref ref-type="aff" rid="aff04">4</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Cruz</surname>
            <given-names>Gustavo Gavina da</given-names>
          </name>
          <xref ref-type="aff" rid="aff01">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Quaresma</surname>
            <given-names>Jos&#233; Carlos do Vale</given-names>
          </name>
          <xref ref-type="aff" rid="aff01">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Lugon</surname>
            <given-names>Jocemir Ronaldo</given-names>
          </name>
          <xref ref-type="aff" rid="aff03">3</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Guimar&#227;es</surname>
            <given-names>Fernando Silva</given-names>
          </name>
          <xref ref-type="aff" rid="aff04">4</xref>
          <xref ref-type="aff" rid="aff07">7</xref>
          <xref ref-type="corresp" rid="c01"/>
        </contrib>
      </contrib-group>
      <aff id="aff01">
        <label>1</label>
        <institution content-type="orgname">Universidade Federal do Rio de Janeiro</institution>
        <institution content-type="orgdiv1">Hospital Universit&#225;rio Clementino Fraga Filho</institution>
        <institution content-type="orgdiv2">Programa de Tratamento Multidisciplinar da Obesidade</institution>
        <addr-line>
          <named-content content-type="city">Rio de Janeiro</named-content>
          <named-content content-type="state">RJ</named-content>
        </addr-line>
        <country country="BR">Brazil</country>
        <institution content-type="original">Programa de Tratamento Multidisciplinar da Obesidade do Hospital Universit&#225;rio Clementino Fraga Filho da Universidade Federal do Rio de Janeiro &#8211; UFRJ &#8211; Rio de Janeiro, RJ &#8211; Brazil</institution>
        <institution content-type="normalized">Universidade Federal do Rio de Janeiro</institution>
      </aff>
      <aff id="aff02">
        <label>2</label>
        <institution content-type="orgname">Centro Universit&#225;rio Anhanguera Niter&#243;i</institution>
        <institution content-type="orgdiv1">Departamento de Fisioterapia</institution>
        <addr-line>
          <named-content content-type="city">Niter&#243;i</named-content>
          <named-content content-type="state">RJ</named-content>
        </addr-line>
        <country country="BR">Brazil</country>
        <institution content-type="original">Departamento de Fisioterapia do Centro Universit&#225;rio Anhanguera Niter&#243;i &#8211; UNIAN, Niter&#243;i, RJ &#8211; Brazil</institution>
        <institution content-type="normalized">Centro Universit&#225;rio Anhanguera Niter&#243;i</institution>
      </aff>
      <aff id="aff03">
        <label>3</label>
        <institution content-type="orgname">Universidade Federal Fluminense</institution>
        <institution content-type="orgdiv1">Faculdade de Medicina</institution>
        <institution content-type="orgdiv2">Divis&#227;o de Nefrologia</institution>
        <addr-line>
          <named-content content-type="city">Niter&#243;i</named-content>
          <named-content content-type="state">RJ</named-content>
        </addr-line>
        <country country="BR">Brazil</country>
        <institution content-type="original">Divis&#227;o de Nefrologia &#8211; Faculdade de Medicina da Universidade Federal Fluminense &#8211; UFF, Niter&#243;i, RJ &#8211; Brazil</institution>
        <institution content-type="normalized">Universidade Federal Fluminense</institution>
      </aff>
      <aff id="aff04">
        <label>4</label>
        <institution content-type="orgname">Universidade Federal do Rio de Janeiro</institution>
        <institution content-type="orgdiv1">Departamento de Fisioterapia</institution>
        <addr-line>
          <named-content content-type="city">Rio de Janeiro</named-content>
          <named-content content-type="state">RJ</named-content>
        </addr-line>
        <country country="BR">Brazil</country>
        <institution content-type="original">Departamento de Fisioterapia da Universidade Federal do Rio de Janeiro &#8211; UFRJ, Rio de Janeiro, RJ &#8211; Brazil</institution>
        <institution content-type="normalized">Universidade Federal do Rio de Janeiro</institution>
      </aff>
      <aff id="aff05">
        <label>5</label>
        <institution content-type="orgname">Universidade Federal Fluminense</institution>
        <institution content-type="orgdiv1">Programa de p&#243;s&#8209;gradua&#231;&#227;o em Ci&#234;ncias M&#233;dicas</institution>
        <addr-line>
          <named-content content-type="city">Niter&#243;i</named-content>
          <named-content content-type="state">RJ</named-content>
        </addr-line>
        <country country="BR">Brazil</country>
        <institution content-type="original">Programa de p&#243;s&#8209;gradua&#231;&#227;o em Ci&#234;ncias M&#233;dicas, Universidade Federal Fluminense &#8211; UFF, Niter&#243;i, RJ &#8211; Brazil</institution>
        <institution content-type="normalized">Universidade Federal Fluminense</institution>
      </aff>
      <aff id="aff06">
        <label>6</label>
        <institution content-type="orgname">Instituto Federal de Educa&#231;&#227;o, Ci&#234;ncia e Tecnologia do Rio de Janeiro</institution>
        <addr-line>
          <named-content content-type="city">Rio de Janeiro</named-content>
          <named-content content-type="state">RJ</named-content>
        </addr-line>
        <country country="BR">Brazil</country>
        <institution content-type="original">Instituto Federal de Educa&#231;&#227;o, Ci&#234;ncia e Tecnologia do Rio de Janeiro, Rio de Janeiro, RJ &#8211; Brazil</institution>
        <institution content-type="normalized">Instituto Federal de Educa&#231;&#227;o, Ci&#234;ncia e Tecnologia do Rio de Janeiro</institution>
      </aff>
      <aff id="aff07">
        <label>7</label>
        <institution content-type="orgname">Centro Universit&#225;rio Augusto Motta</institution>
        <institution content-type="orgdiv1">Programa de p&#243;s-gradua&#231;&#227;o em Ci&#234;ncias da Reabilita&#231;&#227;o</institution>
        <addr-line>
          <named-content content-type="city">Rio de Janeiro</named-content>
          <named-content content-type="state">RJ</named-content>
        </addr-line>
        <country country="BR">Brazil</country>
        <institution content-type="original">Programa de p&#243;s-gradua&#231;&#227;o em Ci&#234;ncias da Reabilita&#231;&#227;o &#8211; Centro Universit&#225;rio Augusto Motta, Rio de Janeiro, RJ &#8211; Brazil</institution>
        <institution content-type="normalized">Centro Universit&#225;rio Augusto Motta</institution>
      </aff>
      <author-notes>
        <corresp id="c01"><bold>Mailing Address: Fernando Silva Guimar&#227;es</bold> , Faculdade de Medicina da Universidade Federal do Rio de Janeiro. Av. Carlos Chagas Filho, 373, Edif&#237;cio do Centro de Ci&#234;ncias da Sa&#250;de, Bloco K, 2&#186; andar, Sala 49 - Cidade Universit&#225;ria - Ilha do Fund&#227;o. Postal Code, 21.941-902, Rio de Janeiro, RJ &#8211; Brazil. E-mail: <email>fguimaraes_pg@yahoo.com.br</email>, <email>fguimaraes.pg@gmail.com</email>
					</corresp>
        <fn fn-type="con">
          <p>
            <bold>Author contributions</bold>
          </p>
          <p>Conception and design of the research: Sant Ann Junior M, Carneiro JRI, Lugon JR, Guimar&#227;es FS; Acquisition of data: Sant Ann Junior M, Carvalhal RF, Torres DFM; Analysis and interpretation of the data: Sant Ann Junior M, Carneiro JRI, Cruz GG, Quaresma JCV, Lugon JR, Guimar&#227;es FS; Statistical analysis: Sant Ann Junior M, Lugon JR, Guimar&#227;es FS; Writing of the manuscript and Critical revision of the manuscript for intellectual content: Sant Ann Junior M, Carneiro JRI, Carvalhal RF, Torres DFM, Cruz GG, Quaresma JCV, Lugon JR, Guimar&#227;es FS.</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 pub-type="epub">
        <day>03</day>
        <month>11</month>
        <year>2015</year>
      </pub-date>
      <pub-date pub-type="collection">
        <month>12</month>
        <year>2015</year>
      </pub-date>
      <volume>105</volume>
      <issue>6</issue>
      <fpage>580</fpage>
      <lpage>587</lpage>
      <history>
        <date date-type="received">
          <day>23</day>
          <month>03</month>
          <year>2015</year>
        </date>
        <date date-type="accepted">
          <day>27</day>
          <month>07</month>
          <year>2015</year>
        </date>
      </history>
      <permissions>
        <license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by/4.0/">
          <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>Morbid obesity is directly related to deterioration in cardiorespiratory capacity, including changes in cardiovascular autonomic modulation.</p>
        </sec>
        <sec>
          <title>Objective:</title>
          <p>This study aimed to assess the cardiovascular autonomic function in morbidly obese individuals.</p>
        </sec>
        <sec>
          <title>Methods:</title>
          <p>Cross-sectional study, including two groups of participants: Group I, composed by 50 morbidly obese subjects, and Group II, composed by 30 nonobese subjects. The autonomic function was assessed by heart rate variability in the time domain (standard deviation of all normal RR intervals [SDNN]; standard deviation of the normal R-R intervals [SDNN]; square root of the mean squared differences of successive R-R intervals [RMSSD]; and the percentage of interval differences of successive R-R intervals greater than 50 milliseconds [pNN50] than the adjacent interval), and in the frequency domain (high frequency [HF]; low frequency [LF]: integration of power spectral density function in high frequency and low frequency ranges respectively). Between-group comparisons were performed by the Student&#8217;s t-test, with a level of significance of 5%.</p>
        </sec>
        <sec>
          <title>Results:</title>
          <p>Obese subjects had lower values of SDNN (40.0 &#177; 18.0 ms vs. 70.0 &#177; 27.8 ms; p = 0.0004), RMSSD (23.7 &#177; 13.0 ms vs. 40.3 &#177; 22.4 ms; p = 0.0030), pNN50 (14.8 &#177; 10.4 % vs. 25.9 &#177; 7.2%; p = 0.0061) and HF (30.0 &#177; 17.5 Hz vs. 51.7 &#177; 25.5 Hz; p = 0.0023) than controls. Mean LF/HF ratio was higher in Group I (5.0 &#177; 2.8 vs. 1.0 &#177; 0.9; p = 0.0189), indicating changes in the sympathovagal balance. No statistical difference in LF was observed between Group I and Group II (50.1 &#177; 30.2 Hz vs. 40.9 &#177; 23.9 Hz; p = 0.9013).</p>
        </sec>
        <sec>
          <title>Conclusion:</title>
          <p>morbidly obese individuals have increased sympathetic activity and reduced parasympathetic activity, featuring cardiovascular autonomic dysfunction.</p>
        </sec>
      </abstract>
      <kwd-group xml:lang="en">
        <title>Keywords:</title>
        <kwd>Obesity, Morbid</kwd>
        <kwd>Cardiovascular Diseases</kwd>
        <kwd>Risk Factors, Pulmonary Heart Disease / complications</kwd>
        <kwd>Heart Rate</kwd>
      </kwd-group>
    </article-meta>
  </front>
  <body>
    <sec sec-type="intro">
      <title>Introduction</title>
      <p>The prevalence of obesity, which is considered an alarming public health problem in the world, has increased dramatically in recent years and become an epidemic<xref ref-type="bibr" rid="B01">1</xref><sup>,</sup><xref ref-type="bibr" rid="B02">2</xref>, including in Brazil<xref ref-type="bibr" rid="B03">3</xref>. Obesity has a multifactorial etiology that encompasses nutritional, genetic, psychic, socioeconomic factors and sedentary lifestyle<xref ref-type="bibr" rid="B01">1</xref><sup>-</sup><xref ref-type="bibr" rid="B03">3</xref>. Excess body weight is associated with cardiovascular, cerebrovascular, respiratory, metabolic and oncologic diseases<xref ref-type="bibr" rid="B04">4</xref><sup>-</sup><xref ref-type="bibr" rid="B07">7</xref>.</p>
      <p>Obesity may be classified using the Body Mass Index (BMI); a BMI varying from 30 kg/m<sup>2</sup>to 34.9 kg/m<sup>2</sup> is classified as class I obesity, 35 kg/m<sup>2</sup>to 39.9 kg/m<sup>2</sup> as class II obesity, and a BMI &#8805; 40 kg/m<sup>2</sup>as class III obesity, also known as morbid obesity<xref ref-type="bibr" rid="B01">1</xref><sup>,</sup><xref ref-type="bibr" rid="B04">4</xref>. Some authors suggest the inclusion of further categories, a BMI ranging from 30 kg/m<sup>2</sup>to 34.9 kg/m<sup>2</sup> for super-obese, BMI &#8805; 60 kg/m<sup>2</sup> for super-super obese<xref ref-type="bibr" rid="B08">8</xref>.</p>
      <p>Morbid obesity is directly associated with deterioration of cardiorespiratory capacity, leading to reduction of pulmonary capacity and functional residual capacity<xref ref-type="bibr" rid="B09">9</xref><sup>,</sup><xref ref-type="bibr" rid="B10">10</xref>, hypoventilation syndrome<xref ref-type="bibr" rid="B11">11</xref><sup>,</sup><xref ref-type="bibr" rid="B12">12</xref>, obstructive sleep apnea<xref ref-type="bibr" rid="B13">13</xref>, increased respiratory muscle strength<xref ref-type="bibr" rid="B14">14</xref>, and changes in the autonomic function<xref ref-type="bibr" rid="B15">15</xref><sup>,</sup><xref ref-type="bibr" rid="B16">16</xref>.</p>
      <p>Assessment of heart rate variability (HRV) quantifies the oscillations in the interval between consecutive heartbeats (R-R intervals), and oscillations between consecutive instantaneous heart rates. HRV may be evaluated either in short or long periods, and its main advantage is the selectivity and non-invasiveness in assessing the cardiovascular autonomic function<xref ref-type="bibr" rid="B17">17</xref><sup>,</sup><xref ref-type="bibr" rid="B18">18</xref>.</p>
      <p>Changes in the autonomic modulation, particularly the reduction of HRV, are risk factors for sudden death in conditions like post-acute myocardial infarction and heart failure<xref ref-type="bibr" rid="B19">19</xref><sup>,</sup><xref ref-type="bibr" rid="B20">20</xref>. Changes in HRV responses are a valuable, early indicator of impairment of cardiovascular health.</p>
      <p>The hypothesis of this study was that the cardiovascular autonomic function is affected by obesity and becomes an additional cardiovascular risk in this population<xref ref-type="bibr" rid="B21">21</xref><sup>-</sup><xref ref-type="bibr" rid="B23">23</xref>. The aim of this study was to assess the cardiovascular autonomic function in morbidly obese individuals.</p>
    </sec>
    <sec sec-type="methods">
      <title>Methods</title>
      <p>This was a cross-sectional study on 80 subjects aged from 20 to 60 years recruited in the Bariatric Surgery Program of the Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro (PROCIBA - HUCFF / UFRJ). Subjects were divided into two groups, Group I, composed of 50 morbidly obese individuals, and Group II, composed of 30 nonobese individuals, matched for age and height. All participants signed an informed consent document, according to the Brazilian National Council for Health (resolution number 466/12). The study was approved by the institutional research ethics committee (Comit&#234; de &#201;tica em Pesquisa do HUCFF-UFRJ, number 077/09).</p>
      <p>The following exclusion criteria were adopted: hemodynamic instability at evaluation, heart failure (identified by the two-dimensional transthoracic echocardiography), obstructive pulmonary disease (forced expiratory volume in the first second [FEV1]/forced vital capacity [FVC] &lt; 70% and FEV1 &lt; 70% of predicted), smoking, history of sleep apnea and/or diurnal hypersomnolence, measured by the Epworth scale<xref ref-type="bibr" rid="B24">24</xref>. Anthropometric assessment was performed by measures of body weight (using an InBody 230, Biospace, Seoul, Korea), height, BMI, and waist-to-hip ratio (WHR)<xref ref-type="bibr" rid="B25">25</xref>.</p>
      <sec>
        <title>Forced Spirometry</title>
        <p>Spirometry was performed according to the American Thoracic Society<xref ref-type="bibr" rid="B26">26</xref> and the Brazilian Society of Pneumology<xref ref-type="bibr" rid="B27">27</xref>guidelines, using a computerized spirometer and its components, including a Lilly-type pneumotachograph (Erich Jaeger, Hoechberg, Germany), volume and flow transducers (Sensym SLP004D, Honeywell Sensing and Control, Golden Valley, MN, USA), following the manufacturers&#8217; protocol. Predicted values were calculated using the equations proposed by Pereira et al<xref ref-type="bibr" rid="B28">28</xref>.</p>
      </sec>
      <sec>
        <title>Assessment of static respiratory pressures</title>
        <p>Assessment of respiratory muscle strength was conducted by measurements of maximal inspiratory and expiratory pressures (IP<sub>max</sub> and EP<sub>max</sub>respectively), according to the methods described by Black &amp; Hyatt<xref ref-type="bibr" rid="B29">29</xref>. An aneroid mannometer/vacuometer (M120 - Comercial M&#233;dica - S&#227;o Paulo - Brazil) and a mouthpiece containing a 2 mm-hole aiming to dissipate pressures generated by facial and oropharyngeal muscles were used. Three measures were obtained from each participant, with a 2-min interval between them, and the best measures obtained in both groups were considered for analysis. Predicted values were those referred by the Brazilian Society of Pneumology and Tuberculosis Pulmonary Function Test Guidelines<xref ref-type="bibr" rid="B27">27</xref>.</p>
      </sec>
      <sec>
        <title>Heart rate variability</title>
        <p>The cardiovascular autonomic function was assessed by analysis of HRV in the time domain and frequency domain. All subjects were instructed to abstain from coffee, tea, and cola and cocoa beverages for at least two hours prior to the test, and to refrain from physical exercise for twenty-four hours before the test.</p>
        <p>Heart rate was recorded under resting condition in sitting position between 8 and 10 o&#8217;clock in the morning to avoid influences of the circadian rhythm on heart rate and HRV. A heart rate monitor (S810 - Polar<sup>&#174;</sup> - Kempele - Finland) was used over a 15-minute period and the beat-to-beat heart rate was recorded through infrared signals<xref ref-type="bibr" rid="B30">30</xref>. Subjects were also instructed not to talk or move during the acquisition of signs, which was performed in a quiet, silent, temperature controlled (21&#186;C - 23&#186;C) room. HRV analysis was performed using the Kubios HRV software, version 2.0 (Kuopio - Finland). For the spectral analysis of HRV, R-R interval time series were analyzed by fast Fourier transform<xref ref-type="bibr" rid="B31">31</xref>. The first two minutes of the test were not included in calculation of HRV to avoid signal instability and artifacts.</p>
      </sec>
      <sec>
        <title>Analysis of heart rate variability in the frequency domain</title>
        <p>Spectral power was calculated by integrating the function of power spectral density in high frequency range (HF: 0.15 - 0.40 Hz) and low frequency range (LF: 0.04 - 0.15 Hz) into normalized units (un). The spectral components were then expressed as the ratio between high frequency range and low frequency range (HF/LF ratio), which reflects the sympathovagal balance<xref ref-type="bibr" rid="B32">32</xref>.</p>
      </sec>
      <sec>
        <title>Analysis of heart rate variability in the time domain</title>
        <p>Analysis of the HRV in the time domain was determined from the RR intervals, using the mean of 5-minute periods or all the monitoring period. A mean of 100 or more successive R-R intervals was considered, and sudden fluctuations &gt; 25% than preceding interval were excluded to exclude extrasystoles from the analysis. The square root of the mean squared differences of successive R-R intervals (RMSSD), the standard deviation of the normal R-R intervals (SDNN), and the percentage of interval differences of successive R-R intervals greater than 50 milliseconds than the adjacent interval (pNN50) were used for analysis<xref ref-type="bibr" rid="B32">32</xref>.</p>
      </sec>
      <sec>
        <title>Statistical analysis</title>
        <p>Sample size was calculated based on the results of the study by Paschoal et al<xref ref-type="bibr" rid="B06">6</xref>, with a statistical power of 0.8 and significance level of 0.05. Twenty-eight subjects in each group (control and obese) would be needed. The SigmaStat 3.1 software (Jandel Scientific, San Rafael, CA, USA) was used for data analysis and graphs were produced using the SigmaPlot 9.01 software (Jandel Scientific, San Rafael, CA, USA). Data distribution was evaluated by the Shapiro-Wilk test, and group comparisons were performed by the unpaired Student's t test. A p-value &lt; 0.05 was considered statistically significant.</p>
      </sec>
    </sec>
    <sec sec-type="results">
      <title>Results</title>
      <p>Characteristics of anthropometry, diurnal somnolence and heart rate in obese and nonobese groups are depicted in <xref ref-type="table" rid="t01">Table 1</xref>.</p>
      <table-wrap id="t01">
        <label>Table 1</label>
        <caption>
          <title>Characteristic of anthropometry, diurnal somnolence and heart rate in the study group (morbidly obese) and control (nonobese)</title>
        </caption>
        <table frame="hsides" rules="groups">
          <thead>
            <tr>
              <th align="left">
                <bold>Variables</bold>
              </th>
              <th align="center">
                <bold>Morbidly obese (n = 50)</bold>
              </th>
              <th align="center">
                <bold>Nonobese (n = 30)</bold>
              </th>
              <th align="center">
                <bold>p</bold>
              </th>
            </tr>
          </thead>
          <tbody>
            <tr>
              <td align="left">Age (years)</td>
              <td align="center">40.0 &#177; 10.4</td>
              <td align="center">37.6 &#177; 11.5</td>
              <td align="center">0.2947</td>
            </tr>
            <tr>
              <td align="left">Height (m)</td>
              <td align="center">1.64 &#177; 0.09</td>
              <td align="center">1.67 &#177; 0.09</td>
              <td align="center">0.3004</td>
            </tr>
            <tr>
              <td align="left">Body weight (kg)</td>
              <td align="center">138.8 &#177; 33.6</td>
              <td align="center">65.2 &#177; 10.3</td>
              <td align="center">&lt; 0.0001</td>
            </tr>
            <tr>
              <td align="left">BMI (kg/m<sup>2</sup>)</td>
              <td align="center">50.7 &#177; 8.9</td>
              <td align="center">23.2 &#177; 2.2</td>
              <td align="center">&lt; 0.0001</td>
            </tr>
            <tr>
              <td align="left">WC (cm)</td>
              <td align="center">136.3 &#177; 18.8</td>
              <td align="center">80.5 &#177; 9.9</td>
              <td align="center">&lt; 0.0001</td>
            </tr>
            <tr>
              <td align="left">HC (cm)</td>
              <td align="center">143.4 &#177; 17.5</td>
              <td align="center">97.5 &#177; 5.9</td>
              <td align="center">&lt; 0.0001</td>
            </tr>
            <tr>
              <td align="left">WHR</td>
              <td align="center">0.95 &#177; 0.09</td>
              <td align="center">0.84 &#177; 0.08</td>
              <td align="center">&lt; 0.0001</td>
            </tr>
            <tr>
              <td align="left">HR (bpm)</td>
              <td align="center">76 &#177; 13</td>
              <td align="center">71 &#177; 9</td>
              <td align="center">0.3269</td>
            </tr>
            <tr>
              <td align="left">Epworth</td>
              <td align="center">6.8 &#177; 3.2</td>
              <td align="center">7.0 &#177; 3.5</td>
              <td align="center">0.5059</td>
            </tr>
          </tbody>
        </table>
        <table-wrap-foot>
          <fn id="TFN01">
            <p>Values in mean &#177; standard deviation. BMI: Body mass index; WHR: Waist-hip ratio; WC: Waist circumference; HC: Hip circumference; HR: Heart rate.</p>
          </fn>
        </table-wrap-foot>
      </table-wrap>
      <p>In the obese group, 54% (n = 27) of individuals were hypertensive under medical treatment, and 16% (n = 8) had diabetes mellitus. Of the patients using medication, 44% (n = 12) used diuretics, 63% (n = 17) used angiotensin-converting-enzyme inhibitor, 22% (n = 6) used beta-blockers, and 75% (n = 20) metformin. No significant differences were observed in pulmonary function between morbidly obese and obese subjects (<xref ref-type="table" rid="t02">Table 2</xref>), and no participant was diagnosed with pulmonary disease.</p>
      <table-wrap id="t02">
        <label>Table 2</label>
        <caption>
          <title>Spirometric variables and maximal static respiratory pressures in morbidly obese and nonobese subjects</title>
        </caption>
        <table frame="hsides" rules="groups">
          <thead>
            <tr>
              <th align="left">
                <bold>Variables</bold>
              </th>
              <th align="center">
                <bold>Obese (n = 5D)</bold>
              </th>
              <th align="center">
                <bold>Nonobese (n = 3D)</bold>
              </th>
              <th align="center">
                <bold>p</bold>
              </th>
            </tr>
          </thead>
          <tbody>
            <tr>
              <td align="left">FVC (% pred)</td>
              <td align="center">78.7 &#177; 12.3</td>
              <td align="center">100.9 &#177; 10.6</td>
              <td align="center">0.4198</td>
            </tr>
            <tr>
              <td align="left">FEV1 (% pred)</td>
              <td align="center">80.5 &#177; 10.2</td>
              <td align="center">97.4 &#177; 8.0</td>
              <td align="center">0.0978</td>
            </tr>
            <tr>
              <td align="left">FEV<sub>1</sub>/FVC (%)</td>
              <td align="center">85.4 &#177; 6.2</td>
              <td align="center">85.4 &#177; 9.3</td>
              <td align="center">0.2373</td>
            </tr>
            <tr>
              <td align="left">EFP (% pred)</td>
              <td align="center">83.4 &#177; 20.3</td>
              <td align="center">86.6 &#177; 13.3</td>
              <td align="center">0.5750</td>
            </tr>
            <tr>
              <td align="left">MVV (% pred)</td>
              <td align="center">89.2 &#177; 23.4</td>
              <td align="center">89.9 &#177; 15.6</td>
              <td align="center">0.3236</td>
            </tr>
            <tr>
              <td align="left">PI<sub>max</sub> (% pred) </td>
              <td align="center">100.2 &#177; 31.5</td>
              <td align="center">121.7 &#177; 25.5</td>
              <td align="center">0.0572</td>
            </tr>
            <tr>
              <td align="left">PE<sub>max</sub> (% pred) </td>
              <td align="center">107.8 &#177; 30.5</td>
              <td align="center">102.0 &#177; 11.3</td>
              <td align="center">0.2359</td>
            </tr>
          </tbody>
        </table>
        <table-wrap-foot>
          <fn id="TFN02">
            <p>FVC: Forced vital capacity; FEV1: Forced expiratory volume in the first second; EFP: Expiratory flow peak; MVV: Maximal voluntary ventilation; PI<sub>max</sub>: Maximal inspiratory pressure; PE<sub>max</sub>: Maximal expiratory pressure. Values in mean &#177; standard deviation.</p>
          </fn>
        </table-wrap-foot>
      </table-wrap>
      <p>Lower values of RMSSD (40.0 &#177; 18.0 ms <italic>vs.</italic> 70.0 &#177; 27.8 ms; p = 0.0004), RMSSD (23.7 &#177; 13.0 ms <italic>vs.</italic> 40.3 &#177; 22.4 ms; p = 0.0030), pNN5 (14.8 &#177; 10.4% <italic>vs.</italic> 25.9 &#177; 7.2%; p = 0.0061) (<xref ref-type="fig" rid="f01">Figure 1</xref>), HF (30.0 &#177; 17.5 Hz <italic>vs.</italic> 51.7 &#177; 25.5 Hz; p = 0.0023) and LF/HF ratio (5.0 &#177; 2.8 <italic>vs.</italic> 1.0 &#177; 0.9; p = 0.0189) were found in Group I as compared to Group II (<xref ref-type="fig" rid="f02">Figures 2</xref> and <xref ref-type="fig" rid="f03">3</xref>). No significant difference was observed in LF values between the groups (50.1 &#177; 30.2 Hz <italic>vs.</italic> 40.9 &#177; 23.9 Hz; p = 0.9013).</p>
      <fig id="f01">
        <label>Figure 1</label>
        <caption>
          <title>Comparison of heart rate variability in the time domain between morbidly obese and nonobese (control) subjects. HF: High frequency, LF: Low frequency, *p &lt; 0.05.</title>
        </caption>
        <graphic xlink:href="1678-4170-abc-105-06-0580-50125-gf01.jpg"/></fig>
      <fig id="f02">
        <label>Figure 2</label>
        <caption>
          <title>Comparison of heart rate variability in the frequency domain between morbidly obese and nonobese (control) subjects. SDNN: Standard deviation of the normal R-R intervals; RMSDD: Square root of the mean squared differences of successive R-R intervals; pNN50: Percentage of interval differences of successive R-R intervals greater than 50 milliseconds than the adjacent interval; *p &lt; 0.05</title>
        </caption>
        <graphic xlink:href="1678-4170-abc-105-06-0580-50125-gf02.jpg"/></fig>
      <fig id="f03">
        <label>Figure 3</label>
        <caption>
          <title>Power spectrum representation of a morbidly obese volunteer (A = 37 years old, 172.6 kg of body weight, 1.78 m of height and body mass index 54.6 kg/m<sup>2</sup>) and a nonobese volunteer (B = 40 years old, 73.4 kg of body weight, 1.73 m of height and body mass index 24.5 kg/m<sup>2</sup>).</title>
        </caption>
        <graphic xlink:href="1678-4170-abc-105-06-0580-50125-gf03.jpg"/></fig>
    </sec>
    <sec sec-type="discussion">
      <title>Discussion</title>
      <p>This study aimed to evaluate the cardiovascular autonomic function in morbidly obese subjects by HRV analysis, and showed an important reduction in the parasympathetic activity in this group of individuals as compared to healthy controls.</p>
      <p>Assessment of the HRV in the time domain consists in the acquisition of continuous electrocardiographic recordings during short or long periods to obtain the distribution of intervals between the normal RR intervals. Numerous indexes for HRV measurement have been described in the literature based on statistical, arithmetical and geometrical calculations<xref ref-type="bibr" rid="B07">7</xref><sup>,</sup><xref ref-type="bibr" rid="B17">17</xref><sup>,</sup><xref ref-type="bibr" rid="B18">18</xref><sup>,</sup><xref ref-type="bibr" rid="B32">32</xref>.</p>
      <p>Assessment of HRV in the frequency domain is based on the spectral power analysis, which describes the distribution of density as a function of frequency. This analysis depends on the spectral decomposition of HR into its causing components, which are described in terms of the frequency they affect heart rate. The power spectral density may be calculated by fast Fourier transform algorithms or autoregressive models<xref ref-type="bibr" rid="B17">17</xref><sup>,</sup><xref ref-type="bibr" rid="B32">32</xref>.</p>
      <p>Jean-Baptiste Joseph Fourier demonstrated that the signals are generally composed by sinusoidal waves with different widths, phases and frequency response. Also, each periodic signal may be decomposed into its respective waves, hence separating the frequency responses<xref ref-type="bibr" rid="B17">17</xref><sup>,</sup><xref ref-type="bibr" rid="B18">18</xref><sup>,</sup><xref ref-type="bibr" rid="B32">32</xref>.</p>
      <p>Reduced HRV has been indicated by several researchers as a morbidity and mortality predictor in acute myocardial infarction<xref ref-type="bibr" rid="B33">33</xref>, heart failure<xref ref-type="bibr" rid="B34">34</xref> and pulmonary hypertension<xref ref-type="bibr" rid="B35">35</xref>. Evidence from the literature indicates that global mortality is 5.3 times higher in individuals with lower HRV (SDNN &lt; 50 ms), quantified by time domain indexes. Additionally, the predictive power of HRV was independent from other factors<xref ref-type="bibr" rid="B36">36</xref>. In our study, morbidly obese individuals had a low mean SDNN value (40.0 ms). In a cross-sectional study on 25 subjects of both genders, aged 45.1 &#177; 15.2 years, FVC was different between nonobese individuals (BMI from 20 to 25 kg/m<sup>2</sup>) and those with BMI &gt; 25 kg/m<sup>2</sup>. The authors also found a significantly decrease in the parasympathetic activity, indicated by the domains of HF<xref ref-type="bibr" rid="B16">16</xref>. These findings are similar to our results supporting an important reduction of HRV in the frequency domain (HF). However, differently from the study by Molfino et al<xref ref-type="bibr" rid="B16">16</xref>, we did not exclude individuals using cardiovascular drugs, due to elevated BMI of our study group and the need to guarantee their safety.</p>
      <p>Several studies are in agreement with our findings<xref ref-type="bibr" rid="B25">25</xref>. In an investigation on the autonomic cardiovascular function in obesity<xref ref-type="bibr" rid="B21">21</xref>, obese individuals of both genders, aged 42.7 &#177; 9.3 years were divided into three groups according to the BMI ranges. The first group was composed by 17 subjects (BMI 27 - 32 kg/m<sup>2</sup>), the second group by 13 subjects (BMI 33 - 40 kg/m<sup>2</sup>), and the third group by 12 subjects (BMI &gt; 40 kg/m<sup>2</sup>). After analysis of HRV in the frequency domain, the authors observed that BMI increased as HF significantly decreased. These findings are also in consonance with our results, although we did not perform the stratification of patients by BMI, since our study groups were composed by morbidly obese and healthy controls only.</p>
      <p>Similar findings have been demonstrated by a study conducted by Swiss investigators<xref ref-type="bibr" rid="B15">15</xref> evaluating the HRV of normal weight and obese women. Mean age and BMI of the normal weight women were 40.1 &#177; 2.4 years and 21.5 &#177; 0.5 kg/m<sup>2</sup>respectively. The obese women were divided into three groups according to their BMI; the first group was composed by women aged 44.4 &#177; 3.5 and BMI 25 - 30 kg/m<sup>2</sup>, the second group by women aged 42.6 &#177; 1.9 years and BMI 30 - 40 kg/m<sup>2</sup>, and the third group by women aged 35.2 &#177; 2.0 years and BMI &gt; 40 kg/m<sup>2</sup>. Higher baseline heart rate and reduced parasympathetic activity (measured in both time and frequency domains) were found in obese women with BMI &gt; 40 kg/m<sup>2</sup>as compared with obese women with lower BMI and nonobese women. These findings are similar to our results, in addition to similarities between the study groups of both studies, including the mean age in the morbidly obese groups (40.0 &#177; 10.4 <italic>vs.</italic> 37.6 &#177; 11.5 years). Also, similarly to our study, hypertensive, insulin-resistant obese women were not excluded in the study by Sztajzel J et al<xref ref-type="bibr" rid="B15">15</xref>. However, morbidly obese subjects in our study had higher BMI (44.2 &#177; 0.7 kg/m<sup>2</sup><italic>vs.</italic> 50.7 &#177; 8.9 kg/m<sup>2</sup>) and their baseline heart rate was not different as compared to nonobese subjects.</p>
      <p>A Polish study<xref ref-type="bibr" rid="B37">37</xref> evaluated the cardiac autonomic function by HRV in two groups of patients with acute myocardial infarction with clinical hemodynamic and stability (Killip I-II class, without arrhythmic events and/or ventricular dysfunction). The first group was composed by obese, mean age of 54.06 &#177; 7.04 years and BMI of 32.0 &#177; 1.78 kg/m<sup>2</sup>, the second group was composed by nonobese subjects, mean age of 55.26 &#177; 6.62 years and BMI of 23.63 &#177; 1.27 kg/m<sup>2</sup>. The time domain indexes of HRV (SDNN, RMSSD and pNN50) were reduced in obese as compared to nonobese subjects. Additionally, analysis of HRV in the frequency domain revealed that LF and LF/HF ratio were elevated, and HF was reduced, with statistical significance. These findings corroborate our results, which indicated reduced parasympathetic activity in both time (SDNN, RMSSD and pNN50) and frequency domains (HF). It is of note that in none of the studies on HRV and morbid obesity here mentioned the pulmonary function was described. In our study, individuals with obstructive changes (FEV1/FVC &lt; 70% and FEV1 &lt; 70% of predicted) were excluded, since airway obstruction is a contributing factor to the increase in sympathetic activity<xref ref-type="bibr" rid="B38">38</xref><sup>-</sup><xref ref-type="bibr" rid="B40">40</xref>.</p>
      <p>One of the main limitations of this study is that a polysomnographic study aiming to identify and exclude patients with sleep apnea was not performed. In order to reduce this bias, subjects with diurnal somnolence, assessed by the Epworth questionnaire, were excluded. However, despite this limitation, we believe that the present study makes an important contribution to the literature by adding the reduced HRV to other well-known cardiovascular risk factors associated with obesity<xref ref-type="bibr" rid="B21">21</xref><sup>-</sup><xref ref-type="bibr" rid="B23">23</xref>. Therefore, analysis of cardiac autonomic function by HRV may be a useful tool for cardiovascular risk stratification in morbidly obese individuals. Further studies to investigate the impact of pulmonary function and fat distribution on HRV in morbid obesity should be conducted.</p>
    </sec>
    <sec sec-type="conclusions">
      <title>Conclusion</title>
      <p>Morbidly obese individuals have increased sympathetic activity and reduced parasympathetic activity, which features a cardiovascular autonomic dysfunction.</p>
    </sec>
  </body>
  <back>
    <fn-group>
      <fn fn-type="supported-by">
        <p>
          <bold>Sources of Funding</bold>
        </p>
        <p>There were no external funding sources for this study.</p>
      </fn>
      <fn fn-type="other">
        <p>
          <bold>Study Association</bold>
        </p>
        <p>This article is part of the thesis of Doctoral submitted by Carlos Mauricio de Sant Ann Junior, from Universidade Federal Fluminense.</p>
      </fn>
    </fn-group>
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  <sub-article article-type="translation" id="SA1" xml:lang="pt">
    <front-stub>
      <title-group>
        <article-title>Disfun&#231;&#227;o Auton&#244;mica Cardiovascular em Pacientes com Obesidade M&#243;rbida</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Sant Anna</surname>
            <given-names>Maur&#237;cio de</given-names>
            <suffix>Junior</suffix>
          </name>
          <xref ref-type="aff" rid="aff08">1</xref>
          <xref ref-type="aff" rid="aff09">2</xref>
          <xref ref-type="aff" rid="aff12">5</xref>
          <xref ref-type="aff" rid="aff13">6</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Carneiro</surname>
            <given-names>Jo&#227;o Regis Ivar</given-names>
          </name>
          <xref ref-type="aff" rid="aff08">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Carvalhal</surname>
            <given-names>Renata Ferreira</given-names>
          </name>
          <xref ref-type="aff" rid="aff08">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Torres</surname>
            <given-names>Diego de Faria Magalh&#227;es</given-names>
          </name>
          <xref ref-type="aff" rid="aff08">1</xref>
          <xref ref-type="aff" rid="aff11">4</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Cruz</surname>
            <given-names>Gustavo Gavina da</given-names>
          </name>
          <xref ref-type="aff" rid="aff08">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Quaresma</surname>
            <given-names>Jos&#233; Carlos do Vale</given-names>
          </name>
          <xref ref-type="aff" rid="aff08">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Lugon</surname>
            <given-names>Jocemir Ronaldo</given-names>
          </name>
          <xref ref-type="aff" rid="aff10">3</xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Guimar&#227;es</surname>
            <given-names>Fernando Silva</given-names>
          </name>
          <xref ref-type="aff" rid="aff11">4</xref>
          <xref ref-type="aff" rid="aff14">7</xref>
          <xref ref-type="corresp" rid="c02"/>
        </contrib>
      </contrib-group>
      <aff id="aff08">
        <label>1</label>
        <institution content-type="orgname">Universidade Federal do Rio de Janeiro</institution>
        <institution content-type="orgdiv1">Hospital Universit&#225;rio Clementino Fraga Filho</institution>
        <institution content-type="orgdiv2">Programa de Tratamento Multidisciplinar da Obesidade</institution>
        <addr-line>
          <named-content content-type="city">Rio de Janeiro</named-content>
          <named-content content-type="state">RJ</named-content>
        </addr-line>
        <country country="BR">Brasil</country>
        <institution content-type="original">Programa de Tratamento Multidisciplinar da Obesidade do Hospital Universit&#225;rio Clementino Fraga Filho da Universidade Federal do Rio de Janeiro &#8211; UFRJ, Rio de Janeiro, RJ &#8211; Brasil</institution>
        <institution content-type="normalized">Universidade Federal do Rio de Janeiro</institution>
      </aff>
      <aff id="aff09">
        <label>2</label>
        <institution content-type="orgname">Centro Universit&#225;rio Anhanguera Niter&#243;i</institution>
        <institution content-type="orgdiv1">Departamento de Fisioterapia</institution>
        <addr-line>
          <named-content content-type="city">Niter&#243;i</named-content>
          <named-content content-type="state">RJ</named-content>
        </addr-line>
        <country country="BR">Brasil</country>
        <institution content-type="original">Departamento de Fisioterapia do Centro Universit&#225;rio Anhanguera Niter&#243;i &#8211; UNIAN, Niter&#243;i, RJ &#8211; Brasil</institution>
      </aff>
      <aff id="aff10">
        <label>3</label>
        <institution content-type="orgname">Universidade Federal Fluminense</institution>
        <institution content-type="orgdiv1">Faculdade de Medicina</institution>
        <institution content-type="orgdiv2">Divis&#227;o de Nefrologia</institution>
        <addr-line>
          <named-content content-type="city">Niter&#243;i</named-content>
          <named-content content-type="state">RJ</named-content>
        </addr-line>
        <country country="BR">Brasil</country>
        <institution content-type="original">Divis&#227;o de Nefrologia &#8211; Faculdade de Medicina da Universidade Federal Fluminense &#8211; UFF, Niter&#243;i, RJ &#8211; Brasil</institution>
        <institution content-type="normalized">Universidade Federal Fluminense</institution>
      </aff>
      <aff id="aff11">
        <label>4</label>
        <institution content-type="orgname">Universidade Federal do Rio de Janeiro</institution>
        <institution content-type="orgdiv1">Departamento de Fisioterapia</institution>
        <addr-line>
          <named-content content-type="city">Rio de Janeiro</named-content>
          <named-content content-type="state">RJ</named-content>
        </addr-line>
        <country country="BR">Brasil</country>
        <institution content-type="original">Departamento de Fisioterapia da Universidade Federal do Rio de Janeiro &#8211; UFRJ, Rio de Janeiro, RJ &#8211; Brasil</institution>
        <institution content-type="normalized">Universidade Federal do Rio de Janeiro</institution>
      </aff>
      <aff id="aff12">
        <label>5</label>
        <institution content-type="orgname">Universidade Federal Fluminense</institution>
        <institution content-type="orgdiv1">Programa de p&#243;s&#8209;gradua&#231;&#227;o em Ci&#234;ncias M&#233;dicas</institution>
        <addr-line>
          <named-content content-type="city">Niter&#243;i</named-content>
          <named-content content-type="state">RJ</named-content>
        </addr-line>
        <country country="BR">Brasil</country>
        <institution content-type="original">Programa de p&#243;s&#8209;gradua&#231;&#227;o em Ci&#234;ncias M&#233;dicas, Universidade Federal Fluminense &#8211; UFF, Niter&#243;i, RJ &#8211; Brasil</institution>
        <institution content-type="normalized">Universidade Federal Fluminense</institution>
      </aff>
      <aff id="aff13">
        <label>6</label>
        <institution content-type="orgname">Instituto Federal de Educa&#231;&#227;o, Ci&#234;ncia e Tecnologia do Rio de Janeiro</institution>
        <addr-line>
          <named-content content-type="city">Rio de Janeiro</named-content>
          <named-content content-type="state">RJ</named-content>
        </addr-line>
        <country country="BR">Brasil</country>
        <institution content-type="original">Instituto Federal de Educa&#231;&#227;o, Ci&#234;ncia e Tecnologia do Rio de Janeiro, Rio de Janeiro, RJ &#8211; Brasil</institution>
        <institution content-type="normalized">Instituto Federal de Educa&#231;&#227;o, Ci&#234;ncia e Tecnologia do Rio de Janeiro</institution>
      </aff>
      <aff id="aff14">
        <label>7</label>
        <institution content-type="orgname">Centro Universit&#225;rio Augusto Motta</institution>
        <institution content-type="orgdiv1">Programa de p&#243;s-gradua&#231;&#227;o em Ci&#234;ncias da Reabilita&#231;&#227;o</institution>
        <addr-line>
          <named-content content-type="city">Rio de Janeiro</named-content>
          <named-content content-type="state">RJ</named-content>
        </addr-line>
        <country country="BR">Brasil</country>
        <institution content-type="original">Programa de p&#243;s-gradua&#231;&#227;o em Ci&#234;ncias da Reabilita&#231;&#227;o &#8211; Centro Universit&#225;rio Augusto Motta, Rio de Janeiro, RJ &#8211; Brasil</institution>
        <institution content-type="normalized">Centro Universit&#225;rio Augusto Motta</institution>
      </aff>
      <author-notes>
        <corresp id="c02"><bold>Correspond&#234;ncia: Fernando Silva Guimar&#227;es</bold> , Faculdade de Medicina da Universidade Federal do Rio de Janeiro. Av. Carlos Chagas Filho, 373, Edif&#237;cio do Centro de Ci&#234;ncias da Sa&#250;de, Bloco K, 2&#186; andar, Sala 49 &#8211; Cidade Universit&#225;ria &#8211; Ilha do Fund&#227;o. CEP 21.941-902, Rio de Janeiro, RJ &#8211; Brasil. E-mail: <email>fguimaraes_pg@yahoo.com.br</email>; <email>fguimaraes.pg@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: Sant Ann Junior M, Carneiro JRI, Lugon JR, Guimar&#227;es FS; Obten&#231;&#227;o de dados: Sant Ann Junior M, Carvalhal RF, Torres DFM; An&#225;lise e interpreta&#231;&#227;o dos dados: Sant Ann Junior M, Carneiro JRI, Cruz GG, Quaresma JCV, Lugon JR, Guimar&#227;es FS; An&#225;lise estat&#237;stica: Sant Ann Junior M, Lugon JR, Guimar&#227;es FS; Reda&#231;&#227;o do manuscrito e Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do intelectual importante: Sant Ann Junior M, Carneiro JRI, Carvalhal RF, Torres DFM, Cruz GG, Quaresma JCV, Lugon JR, Guimar&#227;es FS.</p>
        </fn>
        <fn fn-type="conflict">
          <p>
            <bold>Potencial conflito de interesse</bold>
          </p>
          <p>Declaro n&#227;o haver conflito de interesses pertinentes.</p>
        </fn>
      </author-notes>
      <abstract>
        <title>Resumo</title>
        <sec>
          <title>Fundamentos:</title>
          <p>A obesidade m&#243;rbida est&#225; diretamente relacionada &#224; deteriora&#231;&#227;o da capacidade cardiorrespirat&#243;ria, incluindo altera&#231;&#245;es na modula&#231;&#227;o auton&#244;mica cardiovascular.</p>
        </sec>
        <sec>
          <title>Objetivo:</title>
          <p>Este estudo teve por objetivo avaliar a fun&#231;&#227;o auton&#244;mica cardiovascular de obesos m&#243;rbidos.</p>
        </sec>
        <sec>
          <title>M&#233;todos:</title>
          <p>Estudo transversal, incluindo dois grupos, Grupo I, composto por 50 obesos m&#243;rbidos, e Grupo II, por 30 indiv&#237;duos n&#227;o obesos. A fun&#231;&#227;o auton&#244;mica foi avaliada pela variabilidade da frequ&#234;ncia card&#237;aca no dom&#237;nio do tempo [desvio padr&#227;o de todos os intervalos R-R normais (SDNN); desvio-padr&#227;o de todos os intervalos R-R normais (SDNN); raiz quadrada das m&#233;dias quadr&#225;ticas das diferen&#231;as dos intervalos R-R sucessivos (RMSSD); e o percentual de diferen&#231;as de intervalo intervalos R-R sucessivos maior que 50 milissegundos (pNN50)] em compara&#231;&#227;o ao adjacente, e no dom&#237;nio da frequ&#234;ncia (HF, do ingl&#234;s, &#8220;<italic>high frequency</italic>&#8221;, e LF, do ingl&#234;s, &#8220;<italic>low frequency</italic>&#8221;: integra&#231;&#227;o da fun&#231;&#227;o da densidade espectral de pot&#234;ncia para as bandas de alta e baixa frequ&#234;ncia, respectivamente). Os grupos foram comparados pelo teste t de Student, considerando-se um n&#237;vel de signific&#226;ncia de 5%.</p>
        </sec>
        <sec>
          <title>Resultados:</title>
          <p>Quando comparados aos controles, os indiv&#237;duos obesos apresentaram valores menores de SDNN (40,0 &#177; 18,0 ms vs. 70,0 &#177; 27,8 ms; p = 0,0004), RMSSD (23,7 &#177; 13,0 ms vs. 40,3 &#177; 22,4 ms; p = 0,0030), pNN50 (14,8 &#177; 10,4 % vs. 25,9 &#177; 7,2%; p = 0,0061) e HF (30,0 &#177; 17,5 Hz vs. 51,7 &#177; 25,5 Hz; p = 0,0023). A rela&#231;&#227;o LF/HF m&#233;dia foi maior no Grupo I (5,0 &#177; 2,8 vs. 1,0 &#177; 0,9; p = 0,0189), refletindo altera&#231;&#227;o no equil&#237;brio simpato-vagal. N&#227;o houve diferen&#231;a estat&#237;stica entre os grupos I e II com rela&#231;&#227;o ao &#237;ndice LF (50,1 &#177; 30,2 Hz vs. 40,9 &#177; 23,9 Hz; p = 0,9013).</p>
        </sec>
        <sec>
          <title>Conclus&#227;o:</title>
          <p>obesos m&#243;rbidos apresentam aumento de atividade simp&#225;tica e redu&#231;&#227;o da atividade parassimp&#225;tica, caracterizando uma disfun&#231;&#227;o auton&#244;mica cardiovascular.</p>
        </sec>
      </abstract>
      <kwd-group xml:lang="pt">
        <title>Palavras-chave:</title>
        <kwd>Obesidade M&#243;rbida</kwd>
        <kwd>Doen&#231;as Cardiovasculares</kwd>
        <kwd>Fatores de Risco; Doen&#231;a Cardiopulmonar / complica&#231;&#245;es</kwd>
        <kwd>Frequ&#234;ncia Card&#237;aca</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <sec sec-type="intro">
        <title>Introdu&#231;&#227;o</title>
        <p>A preval&#234;ncia da obesidade, que &#233; considerada um alarmante problema de sa&#250;de p&#250;blica em todo o mundo, aumentou de forma avassaladora nos &#250;ltimos anos, tornando-se uma epidemia<xref ref-type="bibr" rid="B01">1</xref><sup>,</sup><xref ref-type="bibr" rid="B02">2</xref>, inclusive na popula&#231;&#227;o brasileira<xref ref-type="bibr" rid="B03">3</xref>. Essa desordem tem etiologia multifatorial, com destaque para o papel de fatores nutricionais, gen&#233;ticos, ps&#237;quicos, socioecon&#244;micos e do sedentarismo<xref ref-type="bibr" rid="B01">1</xref><sup>-</sup><xref ref-type="bibr" rid="B03">3</xref>. O excesso de peso est&#225; associado ao surgimento de doen&#231;as cardiovasculares, cerebrovasculares, respirat&#243;rias, metab&#243;licas e oncol&#243;gicas<xref ref-type="bibr" rid="B04">4</xref><sup>-</sup><xref ref-type="bibr" rid="B07">7</xref>.</p>
        <p>A obesidade pode ser classificada utilizando-se o &#237;ndice de massa corporal (IMC), considerando-se para diagn&#243;stico os intervalos de 30 kg/m<sup>2</sup>- 34,9 kg/m<sup>2</sup>obesidade classe I, 35 kg/m<sup>2</sup> - 39,9 kg/m<sup>2</sup>obesidade classe II e &#8805; 40 kg/m<sup>2</sup> obesidade classe III, tamb&#233;m denominada obesidade m&#243;rbida<xref ref-type="bibr" rid="B01">1</xref><sup>,</sup><xref ref-type="bibr" rid="B04">4</xref>. Alguns autores perceberam a necessidade da amplia&#231;&#227;o desta classifica&#231;&#227;o, sendo considerados os intervalos de 50 a 60 kg/m<sup>2</sup> para super-obeso e &gt; 60 kg/m<sup>2</sup>para super-super obeso<xref ref-type="bibr" rid="B08">8</xref>.</p>
        <p>A obesidade m&#243;rbida est&#225; diretamente relacionada &#224; deteriora&#231;&#227;o da capacidade cardiorrespirat&#243;ria, acarretando altera&#231;&#245;es diversas, tais como: redu&#231;&#227;o da capacidade pulmonar total e capacidade residual funcional<xref ref-type="bibr" rid="B09">9</xref><sup>,</sup><xref ref-type="bibr" rid="B10">10</xref>, s&#237;ndrome de hipoventila&#231;&#227;o<xref ref-type="bibr" rid="B11">11</xref><sup>,</sup><xref ref-type="bibr" rid="B12">12</xref>, apneia obstrutiva do sono<xref ref-type="bibr" rid="B13">13</xref>, aumento da for&#231;a muscular respirat&#243;ria<xref ref-type="bibr" rid="B14">14</xref>, al&#233;m de modifica&#231;&#245;es na fun&#231;&#227;o auton&#244;mica<xref ref-type="bibr" rid="B15">15</xref><sup>,</sup><xref ref-type="bibr" rid="B16">16</xref>.</p>
        <p>A avalia&#231;&#227;o da variabilidade da frequ&#234;ncia card&#237;aca (VFC) quantifica as oscila&#231;&#245;es no intervalo entre batimentos card&#237;acos consecutivos (intervalos R-R), assim como oscila&#231;&#245;es entre frequ&#234;ncias card&#237;acas instant&#226;neas consecutivas. A VFC pode ser analisada em curtos e longos per&#237;odos, e sua principal vantagem &#233; a possibilidade de avaliar a fun&#231;&#227;o auton&#244;mica cardiovascular de maneira seletiva e n&#227;o-invasiva<xref ref-type="bibr" rid="B17">17</xref><sup>,</sup><xref ref-type="bibr" rid="B18">18</xref>.</p>
        <p>&#201; bem fundamentado na literatura que altera&#231;&#245;es na modula&#231;&#227;o auton&#244;mica, em especial a redu&#231;&#227;o da VFC, constituem risco para morte s&#250;bita em condi&#231;&#245;es como p&#243;s- infarto agudo do mioc&#225;rdio e insufici&#234;ncia card&#237;aca<xref ref-type="bibr" rid="B19">19</xref><sup>,</sup><xref ref-type="bibr" rid="B20">20</xref>. Modifica&#231;&#245;es nas respostas da VFC s&#227;o um indicador valioso e antecipado de comprometimento &#224; sa&#250;de cardiovascular.</p>
        <p>A hip&#243;tese deste estudo era que a fun&#231;&#227;o auton&#244;mica cardiovascular &#233; influenciada pela obesidade, contribuindo desta forma como mais um fator de risco cardiovascular al&#233;m dos j&#225; descritos para esta popula&#231;&#227;o<xref ref-type="bibr" rid="B21">21</xref><sup>-</sup><xref ref-type="bibr" rid="B23">23</xref>. O objetivo do presente estudo foi analisar a fun&#231;&#227;o auton&#244;mica cardiovascular de indiv&#237;duos obesos m&#243;rbidos.</p>
      </sec>
      <sec sec-type="methods">
        <title>M&#233;todos</title>
        <p>Estudo transversal, no qual foram avaliados 80 indiv&#237;duos entre 20 e 60 anos, recrutados no Programa de Cirurgia Bari&#225;trica do Hospital Universit&#225;rio Clementino Fraga Filho da Universidade Federal do Rio de Janeiro (PROCIBA - HUCFF/UFRJ). Os indiv&#237;duos foram divididos em dois grupos, Grupo 1, composto por 50 obesos m&#243;rbidos, e Grupo 2, composto por 30 indiv&#237;duos n&#227;o obesos, pareados por idade e estatura. Todos assinaram um termo de consentimento livre e esclarecido, conforme resolu&#231;&#227;o n&#186;466/12 do Conselho Nacional de Sa&#250;de. O estudo foi aprovado pelo Comit&#234; de &#201;tica em Pesquisa Institucional (Comit&#234; de &#201;tica em Pesquisa do HUCFF-UFRJ, processo n&#186; 077/09).</p>
        <p>Foram adotados como crit&#233;rios de exclus&#227;o: instabilidade hemodin&#226;mica no momento da avalia&#231;&#227;o, insufici&#234;ncia card&#237;aca (evidenciada por meio de ecocardiograma bi-dimensional transtor&#225;cico), doen&#231;a pulmonar obstrutiva volume expirat&#243;rio for&#231;ado no primeiro segundo (VEF1)/capacidade vital for&#231;ada (CVF) &lt; 70% e VEF<sub>1</sub>&lt; 70% do predito], tabagismo, hist&#243;ria de apneia do sono e/ou hipersonol&#234;ncia diurna avaliada pela escala de <italic>Epworth</italic><xref ref-type="bibr" rid="B24">24</xref>. A avalia&#231;&#227;o antropom&#233;trica foi realizada por medidas de peso corporal (usando balan&#231;a InBody 230, Biospace, Seoul, Cor&#233;ia), estatura, IMC, e rela&#231;&#227;o cintura/quadril (RCQ)<xref ref-type="bibr" rid="B25">25</xref>.</p>
        <sec>
          <title>Espirometria for&#231;ada</title>
          <p>A espirometria foi realizada de acordo com as recomenda&#231;&#245;es da <italic>American Thoracic Society</italic><xref ref-type="bibr" rid="B26">26</xref> e da Sociedade Brasileira de Pneumologia<xref ref-type="bibr" rid="B27">27</xref>, utilizando-se o espir&#244;metro computadorizado e seus componentes: pneumotac&#243;grafo tipo <italic>Lilly</italic> (Erich Jaeger, Hoechberg, Alemanha), transdutores de fluxo e press&#227;o (Sensym SLP004D, Honeywell Sensing and Control, Golden Valley, MN, EUA), respeitando-se as orienta&#231;&#245;es de calibra&#231;&#227;o fornecidas pelos fabricantes. Os valores preditos foram calculados de acordo com as equa&#231;&#245;es de Pereira e cols.<xref ref-type="bibr" rid="B28">28</xref>.</p>
        </sec>
        <sec>
          <title>Avalia&#231;&#227;o das press&#245;es respirat&#243;rias est&#225;ticas</title>
          <p>A avalia&#231;&#227;o da for&#231;a muscular respirat&#243;ria foi realizada por medidas das press&#245;es inspirat&#243;ria e expirat&#243;ria m&#225;ximas (P<sub>Im&#225;x</sub> e P<sub>Em&#225;x</sub>, respectivamente), de acordo com o m&#233;todo descrito por Black e Hyatt<xref ref-type="bibr" rid="B29">29</xref>. Utilizou-se um manovacu&#244;metro anal&#243;gico (M120 - Comercial M&#233;dica - S&#227;o Paulo - Brasil), com o bucal apresentando orif&#237;cio de 2 mm, objetivando dissipar as press&#245;es geradas pela musculatura da face e da orofaringe. Foram realizadas tr&#234;s aferi&#231;&#245;es para cada indiv&#237;duo, com intervalo de dois minutos entre elas, considerando-se para an&#225;lise a melhor medida obtida por ambos os grupos. Os valores preditos usados foram os estabelecidos nas Diretrizes para Testes de Fun&#231;&#227;o Pulmonar da Sociedade Brasileira de Pneumologia e Tisiologia<xref ref-type="bibr" rid="B27">27</xref>.</p>
        </sec>
        <sec>
          <title>Variabilidade da frequ&#234;ncia card&#237;aca</title>
          <p>A avalia&#231;&#227;o da fun&#231;&#227;o auton&#244;mica cardiovascular foi realizada pela an&#225;lise da VFC no dom&#237;nio do tempo e no dom&#237;nio da frequ&#234;ncia. Todos os indiv&#237;duos foram orientados a n&#227;o ingerirem ch&#225;, caf&#233;, bebidas coladas e/ou achocolatadas por um per&#237;odo m&#237;nimo de duas horas anterior ao in&#237;cio da avalia&#231;&#227;o, al&#233;m de n&#227;o realizarem exerc&#237;cio f&#237;sico por per&#237;odo de vinte e quatro horas antes do teste.</p>
          <p>Foi realizado o registro dos batimentos card&#237;acos correspondente &#224; condi&#231;&#227;o de repouso na posi&#231;&#227;o sentada. O registro foi realizado sempre entre 8 e 10 horas da manh&#227; objetivando evitar interfer&#234;ncias do ritmo circadiano sobre a frequ&#234;ncia card&#237;aca, afetando assim os resultados da VFC. Os batimentos card&#237;acos foram registrados por um frequenc&#237;metro (S810 - Polar<sup>&#174;</sup> - Kempele - Finl&#226;ndia) por per&#237;odo de quinze minutos e direcionados a uma interface para capta&#231;&#227;o da frequ&#234;ncia card&#237;aca batimento-a-batimento por sinais infravermelhos<xref ref-type="bibr" rid="B30">30</xref>. Os sujeitos foram orientados a n&#227;o conversar ou se mover durante a aquisi&#231;&#227;o de sinais, que foi realizada em ambiente tranquilo, silencioso, com temperatura controlada entre 21&#186;C e 23 &#186;C. Para a realiza&#231;&#227;o da an&#225;lise espectral da VFC, as s&#233;ries temporais dos intervalos R-R foram submetidas &#224; Transformada R&#225;pida de Fourier utilizando-se o <italic>software</italic> Kubios HRV (vers&#227;o 2.0 - Kuopio - Finl&#226;ndia)<xref ref-type="bibr" rid="B31">31</xref>. Para permitir a estabiliza&#231;&#227;o do sinal e evitar o surgimento de artefatos os dois minutos iniciais dos registros n&#227;o foram utilizados para o c&#225;lculo dos par&#226;metros de VFC.</p>
        </sec>
        <sec>
          <title>An&#225;lise da variabilidade da frequ&#234;ncia card&#237;aca no dom&#237;nio frequ&#234;ncia</title>
          <p>A pot&#234;ncia espectral foi calculada por integra&#231;&#227;o da fun&#231;&#227;o da densidade espectral de pot&#234;ncia para as bandas de alta frequ&#234;ncia (HF: 0,15 - 0,40 Hz) e baixa frequ&#234;ncia (LF: 0,04 - 0,15 Hz) em valores normalizados (un). Posteriormente, os componentes foram expressos como a raz&#227;o entre as bandas de baixa e alta frequ&#234;ncia (raz&#227;o LF/HF), que reflete o balan&#231;o simpato-vagal<xref ref-type="bibr" rid="B32">32</xref>.</p>
        </sec>
        <sec>
          <title>An&#225;lise da variabilidade da frequ&#234;ncia card&#237;aca no dom&#237;nio do tempo</title>
          <p>A an&#225;lise da VFC no dom&#237;nio do tempo foi determinada a partir dos registros dos intervalos R-R, utilizando-se a m&#233;dia das medidas de cinco minutos ou de todo o registro. Foi considerada uma m&#233;dia de 100 ou mais intervalos R-R normais sucessivos, e flutua&#231;&#245;es s&#250;bitas superiores a 25% do intervalo precedente foram exclu&#237;das para abolir fen&#244;menos de extrass&#237;stoles. Foram avaliados a raiz quadrada das m&#233;dias quadr&#225;ticas das diferen&#231;as dos intervalos RR sucessivos (RMSSD), o desvio-padr&#227;o de todos os intervalos RR normais (SDNN), e o percentual de diferen&#231;as de intervalo intervalos R-R sucessivos maior que 50 milissegundos (pNN50) em compara&#231;&#227;o ao adjacente<xref ref-type="bibr" rid="B32">32</xref>.</p>
        </sec>
        <sec>
          <title>An&#225;lise estat&#237;stica</title>
          <p>O tamanho amostral foi calculado utilizando-se como refer&#234;ncia os resultados do estudo de Paschoal e cols.<xref ref-type="bibr" rid="B06">6</xref>, considerando-se o poder do teste estat&#237;stico de 0,8 e o n&#237;vel de signific&#226;ncia de 0,05. Desta forma, estimou-se a necessidade de 28 indiv&#237;duos para cada grupo (controle e obesos). Para an&#225;lise dos resultados e confec&#231;&#227;o dos gr&#225;ficos, foram utilizados os programas SigmaStat 3.1 (Jandel Scientific, San Rafael, CA, USA) e SigmaPlot 9.01 (Jandel Scientific, San Rafael, CA, USA), respectivamente. A distribui&#231;&#227;o dos dados foi verificada pelo teste de Shapiro-Wilk. Os grupos foram comparados por meio do teste t de Student (n&#227;o pareado), considerando-se como diferen&#231;as significativas p &lt; 0,05.</p>
        </sec>
      </sec>
      <sec sec-type="results">
        <title>Resultados</title>
        <p>As caracter&#237;sticas antropom&#233;tricas, de sonol&#234;ncia diurna e de frequ&#234;ncia card&#237;aca dos indiv&#237;duos obesos e n&#227;o obesos est&#227;o descritas na <xref ref-type="table" rid="t03">Tabela 1</xref>.</p>
        <table-wrap id="t03">
          <label>Tabela 1</label>
          <caption>
            <title>Caracter&#237;sticas antropom&#233;tricas, sonol&#234;ncia diurna e frequ&#234;ncia card&#237;aca do grupo de estudo (obesos m&#243;bidos) e grupo controle (n&#227;o obesos)</title>
          </caption>
          <table frame="hsides" rules="groups">
            <thead>
              <tr>
                <th align="left">
                  <bold>Vari&#225;veis</bold>
                </th>
                <th align="center">
                  <bold>Obesos M&#243;rbidos (n = 50)</bold>
                </th>
                <th align="center">
                  <bold>N&#227;o obesos (n = 30)</bold>
                </th>
                <th align="center">
                  <bold>p</bold>
                </th>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td align="left">Idade (anos)</td>
                <td align="center">40,0 &#177; 10,4</td>
                <td align="center">37,6 &#177; 11,5</td>
                <td align="center">0,2947</td>
              </tr>
              <tr>
                <td align="left">Estatura (m)</td>
                <td align="center">1,64 &#177; 0,09</td>
                <td align="center">1,67 &#177; 0,09</td>
                <td align="center">0,3004</td>
              </tr>
              <tr>
                <td align="left">Peso corporal (kg)</td>
                <td align="center">138,8 &#177; 33,6</td>
                <td align="center">65,2 &#177; 10,3</td>
                <td align="center">&lt; 0,0001</td>
              </tr>
              <tr>
                <td align="left">IMC (kg/m<sup>2</sup>)</td>
                <td align="center">50,7 &#177; 8,9</td>
                <td align="center">23,2 &#177; 2,2</td>
                <td align="center">&lt; 0,0001</td>
              </tr>
              <tr>
                <td align="left">CA (cm)</td>
                <td align="center">136,3 &#177; 18,8</td>
                <td align="center">80,5 &#177; 9,9</td>
                <td align="center">&lt; 0,0001</td>
              </tr>
              <tr>
                <td align="left">CQ (cm)</td>
                <td align="center">143,4 &#177; 17,5</td>
                <td align="center">97,5 &#177; 5,9</td>
                <td align="center">&lt; 0,0001</td>
              </tr>
              <tr>
                <td align="left">RCQ</td>
                <td align="center">0,95 &#177; 0,09</td>
                <td align="center">0,84 &#177; 0,08</td>
                <td align="center">&lt; 0,0001</td>
              </tr>
              <tr>
                <td align="left">FC (bpm)</td>
                <td align="center">76 &#177; 13</td>
                <td align="center">71 &#177; 9</td>
                <td align="center">0,3269</td>
              </tr>
              <tr>
                <td align="left">Epworth</td>
                <td align="center">6,8 &#177; 3,2</td>
                <td align="center">7,0 &#177; 3,5</td>
                <td align="center">0,5059</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN03">
              <p>Valores apresentados em m&#233;dia &#177; desvio padr&#227;o. IMC: &#205;ndice de massa corporal; RCQ: Rela&#231;&#227;o cintura-quadril; CA: Circunfer&#234;ncia abdominal; CQ: Circunfer&#234;ncia de quadril; FC: Frequ&#234;ncia card&#237;aca.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
        <p>Dentre os indiv&#237;duos obesos, 54% (n = 27) eram hipertensos em tratamento medicamentoso e 16% (n = 8) eram diab&#233;ticos. Dos indiv&#237;duos que fazem utiliza&#231;&#227;o de medicamentos, 44% (n = 12) utilizavam diur&#233;ticos, 63% (n = 17) utilizavam inibidores de enzima conversora de angiotensina, 22% (n = 6) utilizavam betabloqueadores e 75% (n = 20) utilizavam metformina. N&#227;o houve diferen&#231;as significativas entre a fun&#231;&#227;o pulmonar de obesos m&#243;rbidos quando comparados a n&#227;o obesos (<xref ref-type="table" rid="t04">Tabela 2</xref>) e nenhum participante possu&#237;a diagn&#243;stico de doen&#231;a pulmonar.</p>
        <table-wrap id="t04">
          <label>Tabela 2</label>
          <caption>
            <title>Vari&#225;veis espirom&#233;tricas e press&#245;es respirat&#243;rias est&#225;ticas m&#225;ximas de obesos m&#243;rbidos e n&#227;o obesos</title>
          </caption>
          <table frame="hsides" rules="groups">
            <thead>
              <tr>
                <th align="left">
                  <bold>Vari&#225;veis</bold>
                </th>
                <th align="center">
                  <bold>Obesos (n = 5D)</bold>
                </th>
                <th align="center">
                  <bold>N&#227;o obesos (n = 3D)</bold>
                </th>
                <th align="center">
                  <bold>p</bold>
                </th>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td align="left">CVF (% pred)</td>
                <td align="center">7B,7 &#177; 12,3</td>
                <td align="center">1GG,9 &#177; 1G,6</td>
                <td align="center">G,4198</td>
              </tr>
              <tr>
                <td align="left">VEF<sub>1</sub> (% pred)</td>
                <td align="center">BG,5 &#177; 1G,2</td>
                <td align="center">97,4 &#177; B,G</td>
                <td align="center">G,G978</td>
              </tr>
              <tr>
                <td align="left">VEF<sub>1</sub>/CVF (%)</td>
                <td align="center">B5,4 &#177; 6,2</td>
                <td align="center">85,4 &#177; 9,3</td>
                <td align="center">G,2373</td>
              </tr>
              <tr>
                <td align="left">PFE (% pred)</td>
                <td align="center">B3,4 &#177; 2G,3</td>
                <td align="center">86,6 &#177; 13,3</td>
                <td align="center">G,575G</td>
              </tr>
              <tr>
                <td align="left">VVM (% pred )</td>
                <td align="center">89,2 &#177; 23,4</td>
                <td align="center">89,9 &#177; 15,6</td>
                <td align="center">G,3236</td>
              </tr>
              <tr>
                <td align="left">P<sub>Im&#225;x</sub> (% pred)</td>
                <td align="center">1GG,2 &#177; 31,5</td>
                <td align="center">121,7 &#177; 25,5</td>
                <td align="center">G,G572</td>
              </tr>
              <tr>
                <td align="left">P<sub>Em&#225;x</sub> (% pred)</td>
                <td align="center">1G7,B &#177; 3G,5</td>
                <td align="center">1G2,G &#177; 11,3</td>
                <td align="center">G,2359</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN04">
              <p>CVF: Capacidade vital for&#231;ada; VEF<sub>1</sub>: Volume expirat&#243;rio for&#231;ado no primeiro segundo; PFE: Pico de fluxo expirat&#243;rio; VVM: Ventila&#231;&#227;o volunt&#225;ria m&#225;xima; P<sub>Im&#225;x</sub>: Press&#227;o inspirat&#243;ria m&#225;xima; P<sub>Em&#225;x</sub>: Press&#227;o expirat&#243;ria m&#225;xima. Valores apresentados em m&#233;dia &#177; desvio padr&#227;o.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
        <p>Os obesos apresentaram menores valores de SDNN (40,0 &#177; 18,0 ms <italic>vs.</italic> 70,0 &#177; 27,8 ms; p = 0,0004), RMSSD (23,7 &#177; 13,0 ms <italic>vs.</italic> 40,3 &#177; 22,4 ms; p = 0,0030), pNN50 (14,8 &#177; 10,4 % <italic>vs.</italic> 25,9 &#177; 7,2 %; p = 0,0061) (<xref ref-type="fig" rid="f04">Figura 1</xref>) e HF (30,0 &#177; 17,5 Hz <italic>vs.</italic> 51,7 &#177; 25,5 Hz; p = 0,0023), e maior rela&#231;&#227;o LF/HF do que o grupo de n&#227;o obesos (5,0 &#177; 2,8 <italic>vs.</italic> 1,0 &#177; 0,9; p = 0,0189) (<xref ref-type="fig" rid="f05">Figuras 2</xref> e <xref ref-type="fig" rid="f06">3</xref>). N&#227;o houve diferen&#231;a estat&#237;stica entre obesos e n&#227;o obesos com rela&#231;&#227;o ao &#237;ndice LF (50,1 &#177; 30,2 Hz <italic>vs.</italic> 40,9 &#177; 23,9 Hz; p = 0,9013).</p>
        <fig id="f04">
          <label>Figura 1</label>
          <caption>
            <title>Compara&#231;&#227;o da variabilidade da frequ&#234;ncia card&#237;aca no dom&#237;nio do tempo de indiv&#237;duos entre indiv&#237;duos obesos m&#243;rbidos e n&#227;o obesos (controle). HF: Alta frequ&#234;ncia; LF: Baixa frequ&#234;ncia. Signific&#226;ncia estat&#237;stica *p &lt; 0,05.</title>
          </caption>
          <graphic xlink:href="1678-4170-abc-105-06-0580-50125-gf01-pt.jpg"/></fig>
        <fig id="f05">
          <label>Figura 2</label>
          <caption>
            <title>Compara&#231;&#227;o da variabilidade da frequ&#234;ncia card&#237;aca no dom&#237;nio da frequ&#234;ncia entre indiv&#237;duos obesos m&#243;rbidos e n&#227;o obesos (controle). SDNN: Desvio&#8209;padr&#227;o de todos os intervalos R-R normais; RMSSD: Raiz quadrada das m&#233;dias quadr&#225;ticas das diferen&#231;as dos intervalos R-R sucessivos; pNN50: Percentual de diferen&#231;as de intervalo intervalos R-R sucessivos maior que 50 milissegundos em compara&#231;&#227;o ao adjacente. Signific&#226;ncia estat&#237;stica *p &lt; 0,05.</title>
          </caption>
          <graphic xlink:href="1678-4170-abc-105-06-0580-50125-gf02-pt.jpg"/></fig>
        <fig id="f06">
          <label>Figura 3</label>
          <caption>
            <title>Representa&#231;&#227;o do espectro de pot&#234;ncia de um volunt&#225;rio obeso m&#243;rbido (A = 37 anos, peso 172,6 kg, altura 1,78 m e &#237;ndice de massa corporal 54,6 kg/m<sup>2</sup>) e um volunt&#225;rio n&#227;o obeso (B = 40 anos, peso 73,4 kg, altura 1,73 m e &#237;ndice de massa corporal 24,5 kg/m<sup>2</sup>).</title>
          </caption>
          <graphic xlink:href="1678-4170-abc-105-06-0580-50125-gf03-pt.jpg"/></fig>
      </sec>
      <sec sec-type="discussion">
        <title>Discuss&#227;o</title>
        <p>Neste estudo, objetivou-se analisar o comportamento da fun&#231;&#227;o auton&#244;mica cardiovascular em obesos m&#243;rbidos por meio da an&#225;lise da VFC, e se observou que esse grupo de indiv&#237;duos apresenta importante redu&#231;&#227;o da atividade parassimp&#225;tica quando comparado a controles n&#227;o obesos.</p>
        <p>A avalia&#231;&#227;o no dom&#237;nio do tempo consiste na obten&#231;&#227;o de registros eletrocardiogr&#225;ficos cont&#237;nuos em per&#237;odos curtos ou longos, obtendo-se ent&#227;o a dispers&#227;o da dura&#231;&#227;o dos intervalos entre os intervalos R-R normais. Encontra-se descrito na literatura, uma gama de &#237;ndices para mensura&#231;&#227;o da VFC no dom&#237;nio do tempo. Estes &#237;ndices baseiam-se em c&#225;lculos estat&#237;sticos, aritm&#233;ticos e geom&#233;tricos<xref ref-type="bibr" rid="B07">7</xref><sup>,</sup><xref ref-type="bibr" rid="B17">17</xref><sup>,</sup><xref ref-type="bibr" rid="B18">18</xref><sup>,</sup><xref ref-type="bibr" rid="B32">32</xref>.</p>
        <p>A avalia&#231;&#227;o da VFC no dom&#237;nio de frequ&#234;ncia &#233; derivada da an&#225;lise do espectro de pot&#234;ncia que descreve a distribui&#231;&#227;o da densidade em fun&#231;&#227;o da frequ&#234;ncia. Esse tipo de an&#225;lise depende da decomposi&#231;&#227;o espectral da FC em seus componentes causadores, apresentando-os segundo a frequ&#234;ncia com que alteram a FC. O c&#225;lculo da densidade espectral pode ser obtido por algoritmos que utilizam transformadas r&#225;pidas de Fourier ou modelos autorregressivos<xref ref-type="bibr" rid="B17">17</xref><sup>,</sup><xref ref-type="bibr" rid="B32">32</xref>.</p>
        <p>Jean-Baptiste Joseph Fourier demonstrou que, de uma forma geral, os sinais est&#227;o compostos por ondas sinusoidais com diferentes amplitudes, fases e respostas de frequ&#234;ncia, e que cada sinal peri&#243;dico poderia ser desdobrado em suas respectivas ondas, separando-se desta forma suas respostas de frequ&#234;ncia<xref ref-type="bibr" rid="B17">17</xref><sup>,</sup><xref ref-type="bibr" rid="B18">18</xref><sup>,</sup><xref ref-type="bibr" rid="B32">32</xref>.</p>
        <p>A redu&#231;&#227;o da VFC &#233; apontada por diversos pesquisadores como um previsor de morbidade e mortalidade em condi&#231;&#245;es cl&#237;nicas como infarto agudo do mioc&#225;rdio<xref ref-type="bibr" rid="B33">33</xref>, insufici&#234;ncia card&#237;aca<xref ref-type="bibr" rid="B34">34</xref> e hipertens&#227;o pulmonar<xref ref-type="bibr" rid="B35">35</xref>. Relatos da literatura apontam uma mortalidade global 5,3 vezes maior em indiv&#237;duos com menor VFC (SDNN &lt; 50ms) quantificada por &#237;ndices do dom&#237;nio do tempo. Al&#233;m disso, o poder preditivo da VFC para mortalidade global ap&#243;s infarto agudo do mioc&#225;rdio mostrou-se independente de outros fatores<xref ref-type="bibr" rid="B36">36</xref>. Em nosso estudo, participantes obesos m&#243;rbidos apresentaram valor m&#233;dio de SDNN baixo (40,0 ms). Em um estudo transversal envolvendo vinte e cinco indiv&#237;duos de ambos os sexos, com m&#233;dia de idade de 45,1 &#177; 15,2 anos, observaram-se diferen&#231;as na VFC entre indiv&#237;duos n&#227;o obesos (com IMC de 20 a 25 kg/m<sup>2</sup>) e aqueles com IMC &gt; 25 kg/m<sup>2</sup>. Os autores tamb&#233;m observaram uma redu&#231;&#227;o significativa da atividade parassimp&#225;tica, demonstrada pelo dom&#237;nio da HF<xref ref-type="bibr" rid="B16">16</xref>. Esses resultados s&#227;o similares aos obtidos em nosso estudo em que tamb&#233;m foi observada uma importante redu&#231;&#227;o da VFC no dom&#237;nio da frequ&#234;ncia (HF). No entanto, diferentemente do estudo de Molfino e cols.<xref ref-type="bibr" rid="B16">16</xref>, n&#243;s n&#227;o exclu&#237;mos indiv&#237;duos que utilizassem drogas com a&#231;&#227;o cardiovascular, considerando o elevado IMC dos nossos participantes e a necessidade de preserva&#231;&#227;o de sua seguran&#231;a.</p>
        <p>Diversos estudos s&#227;o consonantes com nossos achados<xref ref-type="bibr" rid="B25">25</xref>. Um relato envolvendo a observa&#231;&#227;o do comportamento da fun&#231;&#227;o auton&#244;mica cardiovascular na obesidade<xref ref-type="bibr" rid="B21">21</xref>, indiv&#237;duos obesos de ambos os sexos com m&#233;dia de idade de 42,7 &#177; 9,3 anos foram divididos em tr&#234;s grupos segundo a faixa de IMC. O primeiro grupo foi composto por 17 indiv&#237;duos (IMC na faixa de 27 a 32 kg/m<sup>2</sup>), o segundo por 13 indiv&#237;duos (IMC na faixa de 33 a 40 kg/m<sup>2</sup>), e o terceiro por 12 indiv&#237;duos (IMC &gt; 40 kg/m<sup>2</sup>). Ap&#243;s an&#225;lise da VFC no dom&#237;nio da frequ&#234;ncia, observou-se que &#224; medida que o IMC aumentava, o &#237;ndice HF apresentava importante redu&#231;&#227;o. Esses resultados tamb&#233;m est&#227;o de acordo com nossos achados, apesar n&#227;o de n&#227;o havermos realizado estratifica&#231;&#227;o dos indiv&#237;duos por faixas de IMC, uma vez que nossa amostra era composta apenas por obesos m&#243;rbidos e n&#227;o obesos. Resultados semelhantes foram demonstrados por um estudo realizado por um grupo de pesquisadores su&#237;&#231;os<xref ref-type="bibr" rid="B15">15</xref> que avaliaram a VFC de mulheres eutr&#243;ficas e obesas. As mulheres eutr&#243;ficas tinham m&#233;dia de idade de 40,1 &#177; 2,4 anos e IMC de 21,5 &#177; 0,5 kg/m<sup>2</sup>. As obesas foram divididas em tr&#234;s grupos com diferentes valores de IMC, o primeiro compreendendo mulheres com m&#233;dia de idade de 44,4 &#177; 3,5 anos e IMC na faixa de 25 a 30 kg/m<sup>2</sup>, o segundo com m&#233;dia de idade de 42,6&#177;1,9 anos e IMC na faixa 30 a 40 kg/m<sup>2</sup> e o terceiro com m&#233;dia de idade de 35,4 &#177; 2,0 e IMC &gt; 40 kg/m<sup>2</sup>. Obesas com IMC &gt; 40 kg/m<sup>2</sup> apresentavam uma maior frequ&#234;ncia card&#237;aca basal, e redu&#231;&#227;o da atividade parassimp&#225;tica mensurada tanto no dom&#237;nio do tempo como no dom&#237;nio da frequ&#234;ncia quando comparadas &#224;s obesas de menor IMC e n&#227;o obesas. Esses resultados assemelham-se aos obtidos pelo nosso grupo, al&#233;m da similaridade entre as amostras em ambos os estudos, principalmente quanto &#224; m&#233;dia de idade dos obesos m&#243;rbidos (40,0 &#177; 10,4 <italic>vs.</italic> 37,6 &#177; 11,5 anos). Obesas hipertensas e resistentes &#224; insulina tamb&#233;m n&#227;o foram exclu&#237;das no estudo de Sztajzel e cols. <xref ref-type="bibr" rid="B15">15</xref>, assim como em nosso estudo. Entretanto, os obesos m&#243;rbidos de nosso estudo apresentavam maior IMC (44,2 &#177; 0,7 kg/m<sup>2</sup><italic>vs.</italic> 50,7 &#177; 8,9 kg/m<sup>2</sup>) e sua frequ&#234;ncia card&#237;aca basal n&#227;o foi diferente quando comparada a dos n&#227;o obesos.</p>
        <p>Um estudo polon&#234;s<xref ref-type="bibr" rid="B37">37</xref> avaliou a fun&#231;&#227;o auton&#244;mica cardiovascular pela VFC de dois grupos de indiv&#237;duos com infarto agudo do mioc&#225;rdio sem instabilidade cl&#237;nica e/ou hemodin&#226;mica (classe I e II de Killip, sem altera&#231;&#245;es arr&#237;tmicas e/ou disfun&#231;&#227;o ventricular). O primeiro grupo era composto por obesos com m&#233;dia de idade de 54,06 &#177; 7,04 anos e IMC de 32,0 &#177; 1,78 kg/m<sup>2</sup>, e o segundo, por n&#227;o obesos com m&#233;dia de idade de 55,26 &#177; 6,62 anos e IMC de 23,63 &#177; 1,27 kg/m<sup>2</sup>. Os &#237;ndices de VFC no dom&#237;nio do tempo (SDNN, RMSSD e pNN50) encontravam-se reduzidos nos obesos quando comparados aos n&#227;o obesos. O mesmo comportamento foi observado quando realizada a an&#225;lise da VFC no dom&#237;nio da frequ&#234;ncia, em que os &#237;ndices LF e LF/HF encontravam-se aumentados e HF reduzido, com signific&#226;ncia estat&#237;stica. Esses achados corroboram os encontrados em nosso estudo, em que tamb&#233;m verificamos uma redu&#231;&#227;o da atividade parassimp&#225;tica tanto no dom&#237;nio do tempo (SDNN, RMSSD e pNN50) como no dom&#237;nio da frequ&#234;ncia (HF). Deve-se destacar que em nenhum dos estudos consultados abordando VFC e obesidade m&#243;rbida, a fun&#231;&#227;o pulmonar foi descrita. Em nosso estudo, indiv&#237;duos com altera&#231;&#245;es obstrutivas (VEF<sub>1</sub>/CVF &lt; 70% e VEF<sub>1</sub> &lt;70% dopredito) foram exclu&#237;dos, em virtude de a obstru&#231;&#227;o cr&#244;nica de vias a&#233;reas ser um fator contribuinte para o aumento da atividade simp&#225;tica<xref ref-type="bibr" rid="B38">38</xref><sup>-</sup><xref ref-type="bibr" rid="B40">40</xref>.</p>
        <p>Como principais limita&#231;&#245;es do estudo, podemos citar a aus&#234;ncia de estudo polissonogr&#225;fico que possibilitasse a exclus&#227;o de portadores de apneia obstrutiva do sono. Para minimizar esse vi&#233;s, foram exclu&#237;dos indiv&#237;duos que apresentassem sonol&#234;ncia diurna, avaliada pelo question&#225;rio de <italic>Epworth.</italic> Apesar dessa limita&#231;&#227;o, acreditamos que o presente estudo traz uma contribui&#231;&#227;o importante, por apresentar a redu&#231;&#227;o da VFC como mais um fator de risco cardiovascular associado &#224; obesidade, al&#233;m dos j&#225; conhecidos e destacados pela literatura<xref ref-type="bibr" rid="B21">21</xref><sup>-</sup><xref ref-type="bibr" rid="B23">23</xref>. Sendo assim, a determina&#231;&#227;o do comportamento da fun&#231;&#227;o auton&#244;mica cardiovascular pela an&#225;lise da VFC pode ser utilizada como uma ferramenta de estratifica&#231;&#227;o de risco cardiovascular em obesos m&#243;rbidos. Novos estudos devem ser realizados para investigar fatores como o impacto da fun&#231;&#227;o pulmonar e do padr&#227;o de distribui&#231;&#227;o de gordura na VFC em obesos m&#243;rbidos.</p>
      </sec>
      <sec sec-type="conclusions">
        <title>Conclus&#227;o</title>
        <p>Indiv&#237;duos com obesidade m&#243;rbida apresentam aumento de sua atividade simp&#225;tica e redu&#231;&#227;o da parassimp&#225;tica, caracterizando um desajuste na fun&#231;&#227;o auton&#244;mica cardiovascular.</p>
      </sec>
    </body>
    <back>
      <fn-group>
        <fn fn-type="supported-by">
          <p>
            <bold>Fontes de financiamento</bold>
          </p>
          <p>O presente estudo n&#227;o teve fontes de financiamento externas.</p>
        </fn>
        <fn fn-type="other">
          <p>
            <bold>Vincula&#231;&#227;o acad&#234;mica</bold>
          </p>
          <p>Este artigo &#233; parte de tese de Doutorado de Mauricio de Sant Ann Junior pela Universidade Federal Fluminense.</p>
        </fn>
      </fn-group>
    </back>
  </sub-article>
</article>
