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  <front>
    <journal-meta>
      <journal-id journal-id-type="nlm-ta">Arq Bras Cardiol</journal-id>
      <journal-title-group>
        <journal-title>Arquivos Brasileiros de Cardiologia</journal-title>
        <abbrev-journal-title abbrev-type="publisher">Arq. Bras. Cardiol.</abbrev-journal-title>
      </journal-title-group>
      <issn pub-type="ppub">0066-782X</issn>
      <issn pub-type="epub">1678-4170</issn>
      <publisher>
        <publisher-name>Sociedade Brasileira de Cardiologia</publisher-name>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v3">KjrtGWSxMNgJtL6vWmfhmSd</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v2">S0066-782X2014002300006</article-id>
      <article-id pub-id-type="publisher-id" specific-use="previous-pid">S0066-782X2014005040136</article-id>
      <article-id pub-id-type="other">00006</article-id>
      <article-id pub-id-type="doi">10.5935/abc.20140136</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Original Articles</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title xml:lang="en">Association of Aortic Valve Sclerosis with Previous
               Coronary Artery Disease and Risk Factors</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Marmelo</surname>
            <given-names>Filipe Carvalho</given-names>
          </name>
          <xref ref-type="aff" rid="aff01">
            <sup>1</sup>
          </xref>
          <xref ref-type="corresp" rid="c01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Mateus</surname>
            <given-names>S&#243;nia Matilde Fonseca</given-names>
          </name>
          <xref ref-type="aff" rid="aff01">
            <sup>1</sup>
          </xref>
          <xref ref-type="aff" rid="aff02">
            <sup>2</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Pereira</surname>
            <given-names>Alexandre Jos&#233; Marques</given-names>
          </name>
          <xref ref-type="aff" rid="aff01">
            <sup>1</sup>
          </xref>
          <xref ref-type="aff" rid="aff03">
            <sup>3</sup>
          </xref>
        </contrib>
      </contrib-group>
      <aff id="aff01">
        <label>1</label>
        <institution content-type="orgname">Escola Superior de Sa&#250;de Dr. Lopes Dias </institution>
        <country>Portugal</country>
        <institution content-type="original">Escola Superior de Sa&#250;de Dr. Lopes Dias -
               Portugal</institution>
      </aff>
      <aff id="aff02">
        <label>2</label>
        <institution content-type="orgname">Hospital do Esp&#237;rito Santo de &#201;vora</institution>
        <country>Portugal</country>
        <institution content-type="original">Hospital do Esp&#237;rito Santo de &#201;vora -
               Portugal</institution>
      </aff>
      <aff id="aff03">
        <label>3</label>
        <institution content-type="orgname">Centro Hospitalar Cova da Beira</institution>
        <country>Portugal</country>
        <institution content-type="original">Centro Hospitalar Cova da Beira -
               Portugal</institution>
      </aff>
      <author-notes>
        <corresp id="c01"><bold>Mailing Address: Filipe Carvalho Marmelo,</bold> Rua da Ponte, 13, Potal Code
               6215-439, Paul - Covilh&#227;, Castelo Branco - Portugal. E-mail:
                  <email>filipe.marmelo@hotmail.com</email>
            </corresp>
        <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>12</day>
        <month>09</month>
        <year>2014</year>
      </pub-date>
      <pub-date pub-type="collection">
        <month>11</month>
        <year>2014</year>
      </pub-date>
      <volume>103</volume>
      <issue>5</issue>
      <fpage>398</fpage>
      <lpage>402</lpage>
      <history>
        <date date-type="received">
          <day>11</day>
          <month>01</month>
          <year>2013</year>
        </date>
        <date date-type="rev-recd">
          <day>17</day>
          <month>07</month>
          <year>2014</year>
        </date>
        <date date-type="accepted">
          <day>23</day>
          <month>07</month>
          <year>2014</year>
        </date>
      </history>
      <permissions>
        <license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by-nc/3.0/">
          <license-p>This is an Open Access article distributed under the terms of the Creative
                  Commons Attribution Non-Commercial License which permits unrestricted
                  non-commercial use, distribution, and reproduction in any medium, provided the
                  original work is properly cited. </license-p>
        </license>
      </permissions>
      <abstract xml:lang="en">
        <sec>
          <title>Background:</title>
          <p>Aortic valve sclerosis (AVS) is characterized by increased thickness,
                  calcification and stiffness of the aortic leaflets without fusion of the
                  commissures. Several studies show an association between AVS and presence of
                  coronary artery disease.</p>
        </sec>
        <sec>
          <title>Objective:</title>
          <p>The aim of this study is to investigate the association between presence of AVS
                  with occurrence of previous coronary artery disease and classical risk
                  factors.</p>
        </sec>
        <sec>
          <title>Methods:</title>
          <p>The sample was composed of 2,493 individuals who underwent transthoracic
                  echocardiography between August 2011 and December 2012. The mean age of the cohort
                  was 67.5 &#177; 15.9 years, and 50.7% were female.</p>
        </sec>
        <sec>
          <title>Results:</title>
          <p>The most frequent clinical indication for Doppler echocardiography was the
                  presence of stroke (28.8%), and the most common risk factor was hypertension
                  (60.8%). The most prevalent pathological findings on Doppler echocardiography were
                  mitral valve sclerosis (37.1%) and AVS (36.7%). There was a statistically
                  significant association between AVS with hypertension (p &lt; 0.001), myocardial
                  infarction (p = 0.007), diabetes (p = 0.006) and compromised left ventricular
                  systolic function (p &lt; 0.001). Conclusion: Patients with AVS have higher
                  prevalences of hypertension, stroke, hypercholesterolemia, myocardial infarction,
                  diabetes and compromised left ventricular systolic function when compared with
                  patients without AVS. We conclude that there is an association between presence of
                  AVS with previous coronary artery disease and classical risk factors.</p>
        </sec>
      </abstract>
      <kwd-group xml:lang="en">
        <kwd>Heart Valve Disease/physopathology</kwd>
        <kwd>Coronary Artery Disease</kwd>
        <kwd>Risk Factors</kwd>
        <kwd>Echocardiography, Doppler</kwd>
      </kwd-group>
      <counts>
        <fig-count count="0"/>
        <table-count count="6"/>
        <equation-count count="0"/>
        <ref-count count="18"/>
        <page-count count="5"/>
      </counts>
    </article-meta>
  </front>
  <body>
    <sec sec-type="intro">
      <title>Introduction</title>
      <p>Aortic valve sclerosis (AVS) is characterized by increased thickness, stiffness and
            calcification of the aortic leaflets without fusion of the commissures. Evaluation of
            AVS can be performed with Doppler echocardiography, and its presence can result in
            aortic valve stenosis, which is reflected by increased aortic systolic velocities<xref ref-type="bibr" rid="B01">1</xref><sup>-</sup><xref ref-type="bibr" rid="B04">4</xref>.</p>
      <p>In contrast, acute myocardial infarction (AMI) is one of the main causes of death
            worldwide. This pathology is characterized by accumulation of lipid layers on the
            coronary artery walls through a process of atherosclerosis, resulting in limitation of
            blood flow to the cardiac tissue, which may cause hypoxia of this tissue and, in more
            critical situations, lead to cardiac muscle death<xref ref-type="bibr" rid="B04">4</xref><sup>,</sup><xref ref-type="bibr" rid="B05">5</xref>.</p>
      <p>The relationship between these two pathologies is explained by a progressive release in
            AVS of oxidized low-density lipoprotein that accumulates in the valves and extend
            through the coronary ostia towards the arteries where they are deposited, leading to
            coronary disease. This hypothesis is consistent with findings of histologic and
            immunohistochemistry studies and, even though the mechanism is not yet totally known,
            AVS can be used as a possible significant marker of obstructive coronary artery disease
            (CAD). It is also considered that this association may be explained by the involvement
            of risk factors common to both pathologies, such as age, gender, arterial hypertension
            (AH), smoking, hyperlipidemia and diabetes mellitus (DM)<xref ref-type="bibr" rid="B06">6</xref>.</p>
      <p>Even though the etiological mechanisms of the aortic valve disease and the coronary
            disease have been documented for many years, the relationship between these two
            pathological entities only started to be more sharply investigated in the beginning of
            the 90s after observations, conducted mainly with radiological images, of calcification
            in the coronary vasculature and in the aortic valve<xref ref-type="bibr" rid="B07">7</xref><sup>,</sup><xref ref-type="bibr" rid="B08">8</xref>.</p>
      <p>The main aim of this study is to verify whether there is an association between the
            presence of AVS and CAD.</p>
    </sec>
    <sec sec-type="methods">
      <title>Methods</title>
      <p>This is a transversal, retrospective and descriptive study, based on a convenience
            sample obtained from a database of the ultrasonography laboratory of Hospital do
            Esp&#237;rito Santo de &#201;vora. The study included 2,493 individuals with mean age of 67.5 &#177;
            15.9 years, 50.7% of which were female, who underwent transthoracic Doppler
            echocardiography between August 2011 and December 2012.</p>
      <p>The inclusion criteria for the selection of the sample were all patients undergoing
            transthoracic Doppler echocardiography during the period mentioned above when the aortic
            valvular system was evaluated. Exclusion criteria were defined as all individuals
            undergoing transthoracic Doppler echocardiography outside the period mentioned above,
            individuals undergoing transesophageal echocardiography and individuals without
            information regarding this variable.</p>
      <p>The diagnoses of the pathologies that served as clinical indications for the exam, such
            as heart failure, pulmonary disease, AMI and stroke, were conducted by physicians based
            on clinical history, physical examination and diagnostic tests. Evaluations with
            bidimensional and Doppler echocardiogram were conducted with two ultrasonography
            equipments manufactured by Philips<sup>&#174;</sup>, models IE33 and HD11 XE. AVS was defined
            as an increase in echogenicity and thickness of the aortic leaflets without restriction
            in mobility. Left ventricular systolic function was considered compromised when its
            value, calculated by the Simpson method, was lower than 55% of the ejection fraction.
            Finally, it was defined as dilatation of the left heart chambers when a left ventricular
            diastolic diameter was superior to 32 mm/m<sup>2</sup>and the increase in left atrial
            diameter was above 40 mm<xref ref-type="bibr" rid="B09">9</xref>.</p>
      <p>As for the risk factors, AH was defined as systolic pressure above 140 mmHg, dyastolic
            pressure above 90 mmHg, or use of medication for treatment of AH. Presence of diabetes
            was defined as a level of glucose above 125 mg/dl or treatment for diabetes, without
            distinction between types I and II diabetes. It was defined as smoker an individual with
            current use of tobacco and as previous smoker, those who had not used tobacco for more
            than one year. Dyslipidemia was defined as presence of total cholesterol level above 200
            mg/dl or use of medications to treat dyslipedemia<xref ref-type="bibr" rid="B06">6</xref>.</p>
      <p>Statistical analysis of all collected data was computerized with SPSS<sup>&#174;</sup>
            (Statistical Package for the Social Science) for Windows<sup>&#174;</sup>, version 20.0.
            Initially, a description and characterization of the studied variables was performed in
            order to establish a general profile of the sample. Later, an analysis of the results
            was conducted with a descriptive and correlative statistical analysis.</p>
      <p>Continuous variables were defined as mean&#177;standard deviation (<overline>X</overline>&#177;DP)
            and categorical variables as number (n) and percentage (%).</p>
      <p>The chi-square test of independence was conducted to correlate categorical variables,
            and the chi-square test of goodness of fit was performed to evaluate significant
            differences between the prevalences observed in our study with those from other
            studies.</p>
      <p>The level of statistical significance used for interpretation of the tests was p &#8804; 0.05
            for a confidence interval of 95%.</p>
      <p>The study was conducted with approval from the Ethics Committee of Escola Superior de
            Sa&#250;de Dr. Lopes Dias and Hospital Espirito Santo de &#201;vora.</p>
      <p>The investigation team declares that the study was conducted without external financial
            sources and with all the expenses paid by the authors.</p>
    </sec>
    <sec sec-type="results">
      <title>Results</title>
      <p>The sample of this study was composed of a total of 2,493 invidivuals with mean age of
            67.5 &#177; 15.9 years (<overline>X</overline>&#177;DP), of which 50.7% were females (<xref ref-type="table" rid="t01">Table 1</xref>).</p>
      <table-wrap id="t01">
        <label>Table 1</label>
        <caption>
          <title>Characterization of the sample relative to gender</title>
        </caption>
        <table frame="hsides" rules="rows">
          <thead>
            <tr align="center">
              <th align="left">&#160;</th>
              <th>Male</th>
              <th>Female</th>
            </tr>
          </thead>
          <tbody>
            <tr align="center">
              <td align="left">Frequency</td>
              <td>1,228</td>
              <td>1,265</td>
            </tr>
            <tr align="center">
              <td align="left">Percentage</td>
              <td>49.3%</td>
              <td>50.7%</td>
            </tr>
          </tbody>
        </table>
      </table-wrap>
      <p>In <xref ref-type="table" rid="t02">Table 2</xref>, we may observe the frequencies of
            the main studied variables in patients diagnosed with AVS (only main clinical
            indications are displayed).</p>
      <table-wrap id="t02">
        <label>Table 2</label>
        <caption>
          <title>Frequencies of the main studied variables (n = 2,493)</title>
        </caption>
        <table frame="hsides" rules="rows">
          <thead>
            <tr align="center">
              <th colspan="2">Variable</th>
              <th>Frequency (n/%)</th>
            </tr>
          </thead>
          <tbody>
            <tr align="center">
              <td rowspan="5" align="left">Clinical Indication</td>
              <td align="center">Cardiac failure</td>
              <td align="center">329 (13.2%)</td>
            </tr>
            <tr align="center">
              <td align="center">Stroke</td>
              <td align="center">717 (28.8%)</td>
            </tr>
            <tr align="center">
              <td>Pulmonary Disease</td>
              <td>383 (15.4%)</td>
            </tr>
            <tr align="center">
              <td>Myocardial Infarction</td>
              <td>202 (8.2%)</td>
            </tr>
            <tr align="center">
              <td>Others</td>
              <td>862 (34.4%)</td>
            </tr>
            <tr align="center">
              <td rowspan="5" align="left">Risk Factors</td>
              <td align="center">AH</td>
              <td align="center">1,515 (60.8%)</td>
            </tr>
            <tr align="center">
              <td>Hypercholesterolemia</td>
              <td>673 (27%)</td>
            </tr>
            <tr align="center">
              <td>DM</td>
              <td>500 (20.1%)</td>
            </tr>
            <tr align="center">
              <td>Smoking</td>
              <td>120 (4.8%)</td>
            </tr>
            <tr align="center">
              <td>Atrial Fibrillation</td>
              <td>303 (12.2%)</td>
            </tr>
            <tr align="center">
              <td rowspan="4" align="left">Pathological Results on Doppler
                        echocardiography</td>
              <td align="center">Compromised LVSF</td>
              <td align="center">88 (3.5%)</td>
            </tr>
            <tr align="center">
              <td>Enlarged CD</td>
              <td>203 (8.1%)</td>
            </tr>
            <tr>
              <td align="center">MVS</td>
              <td align="center">914 (37.1%)</td>
            </tr>
            <tr align="center">
              <td>AVS</td>
              <td>915 (36.7%)</td>
            </tr>
          </tbody>
        </table>
        <table-wrap-foot>
          <fn id="TFN01t02">
            <p>AH: Arterial hypertension; DM: Diabetes mellitus; LVSF: Left ventricular
                     systolic function; CD: Left cavitary dimensions; MVS: Mitral valve sclerosis;
                     AVS: Aortic valve sclerosis.</p>
          </fn>
        </table-wrap-foot>
      </table-wrap>
      <p>As shown in <xref ref-type="table" rid="t02">Table 2</xref>, the most frequent clinical
            indication was stroke with 28.8%. Of the risk factors, the most frequent was AH with
            60.8%, followed by hypercolesterolemia with 27%. As for the pathological results of
            Doppler echocardiography, mitral valve sclerosis (MVS) was the most frequent with 37.1%,
            followed by AVS with 36.7%.</p>
      <p>After dividing the sample into two groups of patients with and without AVS, the
            chi-square test was conducted as previously described. The group with AVS was composed
            of 915 individuals, whereas the group without AVS had 1,578 individuals. The variables
            related to the clinical indications, risk factors and results of Doppler
            echocardiography were then compared between both groups.</p>
      <p>Following statistical analysis and as shown in <xref ref-type="table" rid="t03">Table
               3</xref>, there were important significant associations with the variables AH (p &lt;
            0.001), AMI (p = 0.007), compromised left systolic function (p &lt; 0.001) and
            compromised segmentar mobility (p &lt; 0.001). In contrast, there was no significant
            association with hypercholesterolemia, stroke and smoking. There was also no significant
            association with gender, with males showing a prevalence of AVS of 17.3% and females of
            19.4%.</p>
      <table-wrap id="t03">
        <label>Table 3</label>
        <caption>
          <title>Results of statistical tests comparing variables between both groups (n =
                  2,493)</title>
        </caption>
        <table frame="hsides" rules="rows">
          <thead>
            <tr align="center">
              <th colspan="2" rowspan="2">Variable</th>
              <th style="border-bottom:hidden">Group with AVS (n = 915)</th>
              <th style="border-bottom:hidden">Group without AVS (n = 1,578)</th>
              <th rowspan="2">p value</th>
            </tr>
            <tr align="center">
              <th>%/(N)</th>
              <th>% (N)</th>
            </tr>
          </thead>
          <tbody>
            <tr align="center">
              <td rowspan="4" align="left">Clinical Indication</td>
              <td>Cardiac failure</td>
              <td align="center">15% (137)</td>
              <td align="center">12.2% (192)</td>
              <td align="center">0.046</td>
            </tr>
            <tr align="center">
              <td>Stroke</td>
              <td align="center">30.7% (281)</td>
              <td align="center">27.6% (436)</td>
              <td align="center">0.101</td>
            </tr>
            <tr>
              <td>Pulmonary Disease</td>
              <td align="center">14.5% (133)</td>
              <td align="center">15.8% (250)</td>
              <td align="center">0.383</td>
            </tr>
            <tr align="center">
              <td>Myocardial Infarction</td>
              <td align="center">10.1% (92)</td>
              <td align="center">7% (110)</td>
              <td align="center">0.007</td>
            </tr>
            <tr align="center">
              <td rowspan="5" align="left">Risk Factors</td>
              <td>AH</td>
              <td align="center">68.5% (627)</td>
              <td align="center">56.3% (888)</td>
              <td align="center">&lt; 0.001</td>
            </tr>
            <tr align="center">
              <td>Hypercholesterolemia</td>
              <td align="center">27.3% (250)</td>
              <td align="center">26.8% (423)</td>
              <td align="center">0.780</td>
            </tr>
            <tr align="center">
              <td>DM</td>
              <td align="center">23% (210)</td>
              <td align="center">18.4% (290)</td>
              <td align="center">0.006</td>
            </tr>
            <tr align="center">
              <td>Smoking</td>
              <td align="center">3.1% (28)</td>
              <td align="center">5.8% (92)</td>
              <td align="center">0.002</td>
            </tr>
            <tr align="center">
              <td>Atrial Fibrillation</td>
              <td align="center">11% (101)</td>
              <td align="center">12.8% (202)</td>
              <td align="center">0.194</td>
            </tr>
            <tr align="center">
              <td rowspan="3" align="left">Pathological Results on Doppler
                        echocardiography</td>
              <td>Compromised LVSF</td>
              <td align="center">9.5% (87)</td>
              <td align="center">0.1% (1)</td>
              <td align="center">&lt; 0.001</td>
            </tr>
            <tr align="center">
              <td>Enlarged CD</td>
              <td align="center">1.9% (17)</td>
              <td align="center">11.8% (186)</td>
              <td align="center">&lt; 0.001</td>
            </tr>
            <tr align="center">
              <td>MVS</td>
              <td align="center">45.6% (404)</td>
              <td align="center">32.3% (510)</td>
              <td align="center">&lt; 0.001</td>
            </tr>
          </tbody>
        </table>
        <table-wrap-foot>
          <fn id="TFN01t03">
            <p>AVS: Aortic valve sclerosis; AMI: Acute myocardial infarction; AH: Arterial
                     hypertension; DM: Diabetes mellitus; LVSF: Left ventricular systolic function;
                     CD: Left cavitary dimensions; MVS: Mitral valve sclerosis.</p>
          </fn>
        </table-wrap-foot>
      </table-wrap>
      <p>It is observed, therefore, a significant relationship between presence of AMI, AH, DM
            and compromised left systolic vertricular in patients with AVS when compared with
            patients without AVS.</p>
    </sec>
    <sec sec-type="discussion">
      <title>Discussion</title>
      <p>As already shown in several studies, AVS may be used as a risk marker for coronary
            disease. Even though its biochemical mechanism has not been completely clarified, this
            relationship is already widely known. Inflammatory and degerative processes are thought
            to affect coronary vases adjacent to this valve system and attack the arteries walls,
            aggravating pre-existent atherosclerotic processes<xref ref-type="bibr" rid="B01">1</xref><sup>-</sup><xref ref-type="bibr" rid="B03">3</xref><sup>,</sup><xref ref-type="bibr" rid="B06">6</xref>.</p>
      <p>In the studied cohort, we could observe a balance between the prevalence of AVS in males
            and females (17.3% / 19.4%), which is consistent with findings from other studies. Also,
            the advanced mean age observed (67.5 years) confirms that AVS, as a degenerative
            pathology, affects mainly older age groups<xref ref-type="bibr" rid="B10">10</xref>.</p>
      <p>As for the prevalences found in this study and comparing them with other reference
            scientific articles regarding AVS, there was a relevant prevalence of stroke in almost
            one third of the sample (28.8%), which is much higher than the rate found by Otto and
            cols. (1999) in which the prevalence of stroke in individuals with AVS was 8%. Despite
            the difference in values from both studies, there was no significance in this study (p =
            0.101) in contrast to the study by Otto et al<xref ref-type="bibr" rid="B11">11</xref>
            (p = 0.003). The prevalence of AMI in that same study was 8.6%, which is almost
            identical to the prevalence of 8.2% in our cohort. In both studies, there was a
            statistical significance in comparison with the control group. As already mentioned, the
            sclerotic process that affects the aortic valve is similar to the aterosclerotic process
            in which the worsening in aortic degeneration may accelarate the development of
            atherosclerotic plaques in the coronary arteries located peripherally to the valvular
            system, thus leading to the ocurrence of symptoms associated with CAD<xref ref-type="bibr" rid="B06">6</xref><sup>,</sup><xref ref-type="bibr" rid="B11">11</xref>.</p>
      <p>In the rates associated with risk factors, AH presented a prevalence of 60.8%, which is
            slightly inferior to 69% found by Hsu et al<xref ref-type="bibr" rid="B07">7</xref>, but
            superior to 51.7% reported by Otto et al<xref ref-type="bibr" rid="B11">11</xref>. As
            for the statistical significances between the group with and without AVS, Hsu et al<xref ref-type="bibr" rid="B07">7</xref> did not observe a significant association in this
            variable, in contrast to the ones observed in this study (p &lt; 0.001) and in the study
            by Otto et al<xref ref-type="bibr" rid="B11">11</xref>. The influence of AH in the
            development of AVS may be explained by the fact that the aortic valve in patients with
            AH is subjected to higher stress due to the elevated pressure exerted on the aortic
            leaflets, leading to damage on the endothelium of the leaflets, similar to what occurs
            in aterosclerotic lesions<xref ref-type="bibr" rid="B03">3</xref><sup>,</sup><xref ref-type="bibr" rid="B12">12</xref>.</p>
      <p>The prevalence of hypercholesterolemia registered in this stduy was 27%, much lower when
            compared with the prevalence of 45% found in the study by Hsu et al<xref ref-type="bibr" rid="B07">7</xref>. In both studies, this variable did not present statistical
            significance. Comparing with the study by Ottoet al<xref ref-type="bibr" rid="B11">11</xref>, the prevalence of DM was 13.1%, without statistical difference when
            compared with the control group (p = 0.9), whereas the value found in this study was
            20.1%, which showed a strong statistical significance when compared with the control
            group (p = 0.006). The absence of significance in hypercholesterolemia was a surprise,
            since the presence of cholesterol is an important factor in the process of valvular
            degeneration. This may have occurred due to the absence of muscular tissue in the aortic
            valves and to the fact that the deposition of cholesterol occurs differently than that
            in the coronary arteries. The absence of significance can also be explained by the low
            number of diagnoses established in the cohort<xref ref-type="bibr" rid="B13">13</xref><sup>,</sup><xref ref-type="bibr" rid="B14">14</xref>.</p>
      <p>In the pathological results found on Doppler echocardiography, a compromised left
            ventricular systolic function had a prevalence of 9.5%, inferior to that reported by
            Rosa et al<xref ref-type="bibr" rid="B10">10</xref> who registered a prevalence of 17.2%
            with a strong statistical significance in both studies (p &lt; 0.001).</p>
      <p>Despite the absence of studies associating AVS and MVS, this last had a prevalence of
            37.1% with a strong statistical significance. Since the organic tissues that compose the
            aortic valve are similar to those of the mitral valve, it would be expected that the
            processes that lead to the development of sclerosis could also occur in both the valves,
            even though their repercussion in the coronary disease may be different due to their
            anatomical situation<xref ref-type="bibr" rid="B05">5 </xref><sup>-</sup><xref ref-type="bibr" rid="B17">17</xref>.</p>
      <p>Finally, the prevalence of AVS was 36.7%, which is superior to 25% observed by Rosa et
               al<xref ref-type="bibr" rid="B10">10</xref>.</p>
      <p>Based on the information presented above comparing this and several reference studies,
            we observe that, with the exception of hypercholesterolemia, AH and compromised left
            ventricular systolic function, the prevalences found in this study are superior,
            reinforcing the existing link between AVS with DM, AMI and stroke.</p>
      <p>These results suggest that patients with AVS have an increased tendency to develop these
            clinical conditions. Medical action should focus especially in these patients in order
            to enhance therapies and improve measures to prevent risk factors.</p>
    </sec>
    <sec sec-type="conclusions">
      <title>Conclusion</title>
      <p>We conclude, therefore, that there is an association between the occurrence of AVS and
            previous occurrence of AMI, DM and compromised left ventricular systolic function. This
            confirms the main hypothesis of this study of an existing association between the
            presence of previous CAD and AVS, similar to the main studies in this area. This
            association may lead to an appreciation of the presence of AVS on ultrasonography exams,
            which can be considered a risk marker for suspicion of CAD<xref ref-type="bibr" rid="B06">6</xref><sup>,</sup><xref ref-type="bibr" rid="B18">18</xref>.</p>
      <p>A limitation of the study is that the sample was selected in a laboratory that assists
            mainly a stroke unit and internal medicine inpatients, which may have influenced the
            prevalence of stroke. Another limitation of the study refers to the absence of
            multivariate analysis, which did not show significant results. As a suggestion for
            future studies, we propose to investigate if MVS, like AVS, could influence the
            occurrence of AMI and if stroke would or would not be an influence. The investigation
            team suggests that there could be an advantage to perform a longitudinal study about
            this theme.</p>
    </sec>
  </body>
  <back>
    <fn-group>
      <fn fn-type="con">
        <p>
          <bold>Author contributions</bold>
        </p>
        <p>Conception and design of the research, Analysis and interpretation of the data,
               Statistical analysis and Critical revision of the manuscript for intellectual
               content: Marmelo FC, Mateus SMF, Pereira AJM; Acquisition of data and Obtaining
               financing: Marmelo FC, Mateus SMF; Writing of the manuscript: Marmelo FC.</p>
      </fn>
      <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 article is part of the degree submitted by Filipe Carvalho Marmelo, from Escola
               Superior de Sa&#250;de Dr. Lopes Dias.</p>
      </fn>
    </fn-group>
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  </back>
  <sub-article article-type="translation" id="SA1" xml:lang="pt">
    <front-stub>
      <title-group>
        <article-title xml:lang="pt">Associa&#231;&#227;o entre Esclerose Valvar A&#243;rtica com Doen&#231;a
               Arterial Coronariana Pr&#233;via e Fatores de Risco</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Marmelo</surname>
            <given-names>Filipe Carvalho</given-names>
          </name>
          <xref ref-type="aff" rid="aff04">
            <sup>1</sup>
          </xref>
          <xref ref-type="corresp" rid="c02"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Mateus</surname>
            <given-names>S&#243;nia Matilde Fonseca</given-names>
          </name>
          <xref ref-type="aff" rid="aff04">
            <sup>1</sup>
          </xref>
          <xref ref-type="aff" rid="aff05">
            <sup>2</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Pereira</surname>
            <given-names>Alexandre Jos&#233; Marques</given-names>
          </name>
          <xref ref-type="aff" rid="aff04">
            <sup>1</sup>
          </xref>
          <xref ref-type="aff" rid="aff06">
            <sup>3</sup>
          </xref>
        </contrib>
      </contrib-group>
      <aff id="aff04">
        <label>1</label>
        <institution content-type="orgname">Escola Superior de Sa&#250;de Dr. Lopes Dias </institution>
        <country>Portugal</country>
        <institution content-type="original">Escola Superior de Sa&#250;de Dr. Lopes Dias -
               Portugal</institution>
      </aff>
      <aff id="aff05">
        <label>2</label>
        <institution content-type="orgname">Hospital do Esp&#237;rito Santo de &#201;vora</institution>
        <country>Portugal</country>
        <institution content-type="original">Hospital do Esp&#237;rito Santo de &#201;vora -
               Portugal</institution>
      </aff>
      <aff id="aff06">
        <label>3</label>
        <institution content-type="orgname">Centro Hospitalar Cova da Beira</institution>
        <country>Portugal</country>
        <institution content-type="original">Centro Hospitalar Cova da Beira -
               Portugal</institution>
      </aff>
      <author-notes>
        <corresp id="c02"><bold>Correspond&#234;ncia: Filipe Carvalho Marmelo,</bold> Rua da Ponte, 13, CEP
               6215-439, Paul - Covilh&#227;, Castelo Branco - Portugal. E-mail:
                  <email>filipe.marmelo@hotmail.com</email></corresp>
      </author-notes>
      <abstract xml:lang="pt">
        <sec>
          <title>Fundamentos:</title>
          <p>A esclerose valvar a&#243;rtica (EVA) &#233; caracterizada por aumento da espessura,
                  endurecimento e calcifica&#231;&#227;o dos folhetos a&#243;rticos sem fus&#227;o das comissuras.
                  V&#225;rios estudos apontam para a exist&#234;ncia de uma rela&#231;&#227;o entre EVA e presen&#231;a de
                  doen&#231;a arterial coronariana.</p>
        </sec>
        <sec>
          <title>Objetivo:</title>
          <p>Este estudo tem como objetivo verificar se existe associa&#231;&#227;o entre a presen&#231;a de
                  EVA e presen&#231;a de doen&#231;a arterial coronariana pr&#233;via e fatores de risco.</p>
        </sec>
        <sec>
          <title>M&#233;todos:</title>
          <p>A amostra foi constitu&#237;da por 2.493 indiv&#237;duos que realizaram ecocardiograma
                  transtor&#225;cico entre agosto de 2011 e dezembro de 2012. A m&#233;dia de idade da amostra
                  foi de 67,5 &#177; 15,9 anos e 50,7% era do g&#234;nero feminino.</p>
        </sec>
        <sec>
          <title>Resultados:</title>
          <p>A indica&#231;&#227;o cl&#237;nica mais frequente para o eco-Doppler card&#237;aco foi o acidente
                  vascular cerebral (28,8%), sendo que 60,8% dos indiv&#237;duos apresentavam hipertens&#227;o
                  arterial. As patologias com maior preval&#234;ncia ao eco-Doppler foram a esclerose
                  valvar mitral (37,1%) e EVA (36,7%). Houve uma associa&#231;&#227;o estatisticamente
                  significativa entre a EVA com hipertens&#227;o arterial (p &lt; 0,001), infarto do
                  mioc&#225;rdio (p = 0,007), diabetes (p = 0,006) e fun&#231;&#227;o sist&#243;lica ventricular
                  esquerda alterada (p &lt; 0,001).</p>
        </sec>
        <sec>
          <title>Conclus&#227;o:</title>
          <p>Pacientes com esclerose valvar a&#243;rtica t&#234;m maior preval&#234;ncia de hipertens&#227;o
                  arterial, acidente vascular cerebral, hipercolesterolemia, infarto do mioc&#225;rdio,
                  diabetes e fun&#231;&#227;o sist&#243;lica ventricular esquerda alterada quando comparados a
                  pacientes sem EVA. Conclui-se que existe uma associa&#231;&#227;o entre presen&#231;a de EVA com
                  doen&#231;a arterial coronariana pr&#233;via e fatores de risco cl&#225;ssicos.</p>
        </sec>
      </abstract>
      <kwd-group xml:lang="pt">
        <kwd>Doen&#231;as das Valvas Card&#237;acas/fisopatologia</kwd>
        <kwd>Doen&#231;a da Art&#233;ria Coronariana</kwd>
        <kwd>Fatores de Risco</kwd>
        <kwd>Ecocardiografia Doppler</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <sec sec-type="intro">
        <title>Introdu&#231;&#227;o</title>
        <p>A esclerose valvar a&#243;rtica (EVA) &#233; caraterizada por aumento da espessura,
               endurecimento e calcifica&#231;&#227;o dos folhetos a&#243;rticos sem fus&#227;o das comissuras. Sua
               avalia&#231;&#227;o pode ser realizada atrav&#233;s do eco-Doppler card&#237;aco, e sua presen&#231;a pode
               ocasionar estenose da valva a&#243;rtica, refletida em um aumento das velocidades
               sist&#243;licas na aorta<xref ref-type="bibr" rid="B01">1</xref><sup>-</sup><xref ref-type="bibr" rid="B04">4</xref>.</p>
        <p>Por outro lado, o infarto agudo do mioc&#225;rdio (IAM) &#233; uma das principais causas de
               morte em todo o mundo. Esta patologia &#233; caracterizada pelo ac&#250;mulo de camadas
               lip&#237;dicas nas paredes das art&#233;rias coron&#225;rias atrav&#233;s do processo de aterosclerose
               levando a uma limita&#231;&#227;o do fluxo sangu&#237;neo ao tecido card&#237;aco, podendo provocar
               hipoxemia deste tecido e, em situa&#231;&#245;es mais cr&#237;ticas, levar &#224; morte do m&#250;sculo
                  card&#237;aco<xref ref-type="bibr" rid="B04">4</xref><sup>,</sup><xref ref-type="bibr" rid="B05">5</xref>.</p>
        <p>A rela&#231;&#227;o entre estas duas patologias explica-se pelo fato da EVA levar, de forma
               progressiva, &#224; libera&#231;&#227;o de lipoprote&#237;nas de baixa densidade oxidadas que se acumulam
               nas valvas e progridem atrav&#233;s dos &#243;stios coron&#225;rios para as art&#233;rias onde se
               depositam, levando &#224; doen&#231;a coronariana. Esta hip&#243;tese &#233; consistente com achados de
               estudos histol&#243;gicos e imuno-histoqu&#237;micos e, apesar do mecanismo ainda n&#227;o ser
               totalmente conhecido, a EVA pode ser utilizada como um poss&#237;vel marcador de
               signific&#226;ncia para doen&#231;a arterial coronariana (DAC) obstrutiva. Considera-se ainda
               que esta rela&#231;&#227;o possa ser explicada pelo envolvimento de fatores de risco comuns &#224;s
               duas patologias como idade, sexo, hipertens&#227;o arterial (HA), tabagismo,
               hiperlipidemia e diabetes mellitus (DM)<xref ref-type="bibr" rid="B06">6</xref>.</p>
        <p>Apesar dos mecanismos etiol&#243;gicos da doen&#231;a valvular a&#243;rtica e da doen&#231;a coronariana
               serem documentados h&#225; v&#225;rios anos, a rela&#231;&#227;o entre estas duas entidades patol&#243;gicas
               come&#231;ou a ser investigada de forma mais incisiva apenas no in&#237;cio da d&#233;cada de 90
               ap&#243;s observa&#231;&#245;es, realizadas principalmente por imagens radiol&#243;gicas, de calcifica&#231;&#227;o
               da anatomia vascular coronariana e da valva a&#243;rtica<xref ref-type="bibr" rid="B07">7</xref><sup>,</sup><xref ref-type="bibr" rid="B08">8</xref>.</p>
        <p>Este estudo tem como objetivo principal verificar se existe rela&#231;&#227;o entre a presen&#231;a
               de EVA e DAC.</p>
      </sec>
      <sec sec-type="methods">
        <title>M&#233;todos</title>
        <p>Este &#233; um um estudo transversal retrospectivo e descritivo, baseado em uma amostra de
               conveni&#234;ncia obtida a partir de uma base de dados do laborat&#243;rio de ultrassonografia
               do Hospital do Esp&#237;rito Santo de &#201;vora. O estudo incluiu 2.493 indiv&#237;duos com m&#233;dia
               de idade de 67,5 &#177; 15,9 anos, sendo 50,7% do g&#234;nero feminino, que foram submetidos &#224;
               realiza&#231;&#227;o de eco-Doppler card&#237;aco transtor&#225;cico entre agosto de 2011 e dezembro de
               2012.</p>
        <p>Os crit&#233;rios de inclus&#227;o para a sele&#231;&#227;o da amostra foram todos os pacientes
               submetidos a eco-Doppler card&#237;aco transtor&#225;cico durante o per&#237;odo referido acima,
               quando foi realizada a avalia&#231;&#227;o do sistema valvular a&#243;rtico. Como crit&#233;rios de
               exclus&#227;o foram definidos todos os indiv&#237;duos submetidos &#224; realiza&#231;&#227;o de eco-Doppler
               card&#237;aco transtor&#225;cico fora do per&#237;odo acima descrito, indiv&#237;duos submetidos &#224;
               realiza&#231;&#227;o de ecocardiograma transesof&#225;gico e indiv&#237;duos sem informa&#231;&#227;o acerca desta
               vari&#225;vel.</p>
        <p>Os diagn&#243;sticos relativos &#224;s patologias das indica&#231;&#245;es cl&#237;nicas como a insufici&#234;ncia
               card&#237;aca, doen&#231;a pulmonar, IAM e acidente vascular cerebral (AVC) foram conduzidos
               por m&#233;dicos com base na hist&#243;ria cl&#237;nica, exame f&#237;sico e exames complementares de
               diagn&#243;stico.</p>
        <p>As avalia&#231;&#245;es ecocardiogr&#225;ficas bidimensional e de Doppler foram realizadas atrav&#233;s
               de dois equipamentos de ultrassonografia da marca Philips<sup>&#174;</sup>, modelos IE33 e
               HD11 XE. A EVA foi definida como aumento da ecogenicidade e espessamento dos folhetos
               a&#243;rticos sem restri&#231;&#227;o na motilidade. Para a fun&#231;&#227;o sist&#243;lica ventricular esquerda,
               definiu-se como alterada quando o valor encontrado pelo m&#233;todo de Simpson foi
               inferior a 55% da fra&#231;&#227;o de eje&#231;&#227;o. Finalmente, foi definida como dilata&#231;&#227;o das
               cavidades esquerdas quando se verificou um valor do di&#226;metro diast&#243;lico do ventr&#237;culo
               esquerdo superior a 32 mm/m<sup>2</sup>e um aumento do di&#226;metro do &#225;trio esquerdo
               superior a 40 mm<xref ref-type="bibr" rid="B09">9</xref>.</p>
        <p>Em rela&#231;&#227;o aos fatores de risco, foi definida como HA o encontro da press&#227;o sist&#243;lica
               superior a 140 mmHg, press&#227;o diast&#243;lica superior a 90 mmHg, ou uso de medica&#231;&#227;o para
               tratamento de HA. A presen&#231;a de DM foi definida como n&#237;vel de glicose superior a 125
               mg/dl ou tratamento para diabetes, sem se fazer distin&#231;&#227;o entre diabetes tipo I e
               tipo II. Definiu-se como tabagista os indiv&#237;duos com consumo atual de tabaco e
               indiv&#237;duos ex-tabagistas, aqueles que n&#227;o consumiam tabaco h&#225; mais de um ano. Foi
               definida como dislipidemia a presen&#231;a de um n&#237;vel de colesterol total superior a 200
               mg/dl ou uso de medicamento neste sentido<xref ref-type="bibr" rid="B06">6</xref>.</p>
        <p>A an&#225;lise estat&#237;stica de todos os dados coletados foi informatizada e tratada com o
               programa SPSS<sup>&#174;</sup> (Statistical Package for the Social Science) para
                  Windows<sup>&#174;</sup>, vers&#227;o 20.0. Inicialmente, realizou-se descri&#231;&#227;o e
               caracteriza&#231;&#227;o das vari&#225;veis em estudo, de modo a estabelecer um perfil geral da
               amostra. Posteriormente, procedeu-se &#224; an&#225;lise dos resultados, efetuando uma
               estat&#237;stica descritiva e correlacional.</p>
        <p>As vari&#225;veis cont&#237;nuas foram definidas como m&#233;dia&#177;desvio padr&#227;o
                  (<overline>X</overline>&#177;DP) e as categ&#243;ricas como n&#250;mero (n) e percentagem
               (%).</p>
        <p>A fim de se relacionar as vari&#225;veis categ&#243;ricas, realizou-se o teste estat&#237;stico de
               qui-quadrado de independ&#234;ncia e para se avaliar a exist&#234;ncia de diferen&#231;as
               significativas entre as preval&#234;ncias observadas no nosso estudo com as de outros
               estudos, foi usado o teste de qui-quadrado de ader&#234;ncia.</p>
        <p>O n&#237;vel de signific&#226;ncia estat&#237;stica utilizado para a interpreta&#231;&#227;o dos testes foi de
               p &#8804; 0,05 para um intervalo de confian&#231;a de 95%.</p>
        <p>A realiza&#231;&#227;o do estudo foi aprovada pelos Conselhos de &#201;tica da Escola Superior de
               Sa&#250;de Dr. Lopes Dias e do Hospital Espirito Santo de &#201;vora.</p>
        <p>A equipe de investiga&#231;&#227;o declara que n&#227;o existiram fontes externas de financiamento
               para a realiza&#231;&#227;o do estudo, tendo sido todas as despesas assumidas pelos
               autores.</p>
      </sec>
      <sec sec-type="results">
        <title>Resultados</title>
        <p>A amostra deste estudo foi constitu&#237;da por um total de 2.493 indiv&#237;duos com uma m&#233;dia
               de idade de 67,5 &#177; 15,9 anos (<overline>X</overline>&#177;DP), sendo que 50,7% eram do
               g&#234;nero feminino (<xref ref-type="table" rid="t04">Tabela 1</xref>).</p>
        <table-wrap id="t04">
          <label>Tabela 1</label>
          <caption>
            <title>Carateriza&#231;&#227;o da amostra em rela&#231;&#227;o ao g&#234;nero</title>
          </caption>
          <table frame="hsides" rules="rows">
            <thead>
              <tr align="center">
                <th align="left">&#160;</th>
                <th>Masculino</th>
                <th>Feminino</th>
              </tr>
            </thead>
            <tbody>
              <tr align="center">
                <td align="left">Frequ&#234;ncia</td>
                <td>1.228</td>
                <td>1.265</td>
              </tr>
              <tr align="center">
                <td align="left">Percentagem</td>
                <td>49,3%</td>
                <td>50,7%</td>
              </tr>
            </tbody>
          </table>
        </table-wrap>
        <p>Na <xref ref-type="table" rid="t05">Tabela 2</xref> &#233; poss&#237;vel observar as
               frequ&#234;ncias das principais vari&#225;veis em estudo nos pacientes diagnosticados com EVA
               (constam apenas as principais indica&#231;&#245;es cl&#237;nicas).</p>
        <table-wrap id="t05">
          <label>Tabela 2</label>
          <caption>
            <title>Frequ&#234;ncias das principais vari&#225;veis em estudo (n = 2.493)</title>
          </caption>
          <table frame="hsides" rules="rows">
            <thead>
              <tr align="center">
                <th colspan="2">Vari&#225;vel</th>
                <th>Frequ&#234;ncia (n/%)</th>
              </tr>
            </thead>
            <tbody>
              <tr align="center">
                <td rowspan="5" align="left">Indica&#231;&#227;o Cl&#237;nica</td>
                <td>Insufici&#234;ncia Card&#237;aca</td>
                <td>329 (13,2%)</td>
              </tr>
              <tr align="center">
                <td>AVC</td>
                <td>717 (28,8%)</td>
              </tr>
              <tr align="center">
                <td>Doen&#231;a Pulmonar</td>
                <td>383 (15,4%)</td>
              </tr>
              <tr align="center">
                <td>Infarto do Mioc&#225;rdio</td>
                <td>202 (8,2%)</td>
              </tr>
              <tr align="center">
                <td>Outras</td>
                <td>862 (34,4%)</td>
              </tr>
              <tr align="center">
                <td rowspan="5" align="left">Fatores de Risco</td>
                <td>HA</td>
                <td>1515 (60,8%)</td>
              </tr>
              <tr align="center">
                <td>Hipercolesterolemia</td>
                <td>673 (27%)</td>
              </tr>
              <tr align="center">
                <td>DM</td>
                <td>500 (20,1%)</td>
              </tr>
              <tr align="center">
                <td>Tabagismo</td>
                <td>120 (4,8%)</td>
              </tr>
              <tr align="center">
                <td>Fibrila&#231;&#227;o Atrial</td>
                <td>303 (12,2%)</td>
              </tr>
              <tr align="center">
                <td rowspan="4" align="left">Resultados Patol&#243;gicos de Eco-Doppler
                           Card&#237;aco</td>
                <td>FSVE alterada</td>
                <td>88 (3,5%)</td>
              </tr>
              <tr align="center">
                <td>DC dilatadas</td>
                <td>203 (8,1%)</td>
              </tr>
              <tr>
                <td align="center">EVM</td>
                <td align="center">914 (37,1%)</td>
              </tr>
              <tr align="center">
                <td>EVA</td>
                <td>915 (36,7%)</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN01t05">
              <p>AVC: Acidente vascular cerebral; HA: Hipertens&#227;o arterial; DM: Diabetes
                        mellitus; FSVE: Fun&#231;&#227;o sist&#243;lica ventricular esquerda; DC: Dimens&#245;es
                        cavit&#225;rias esquerdas; EVM: Esclerose valvar mitral; EVA: Esclerose valvar
                        a&#243;rtica.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
        <p>Como &#233; poss&#237;vel visualizar na <xref ref-type="table" rid="t05">Tabela 2</xref>, a
               indica&#231;&#227;o cl&#237;nica mais frequente foi o AVC com 28,8%. Dos fatores de risco, o mais
               frequente foi a HA com 60,8%, seguido da hipercolesterolemia com 27%. Em rela&#231;&#227;o aos
               resultados patol&#243;gicos do eco-Doppler card&#237;aco, a esclerose valvar mitral (EVM) foi o
               mais frequente com 37,1%, seguido da EVA com 36,7%.</p>
        <p>Ap&#243;s divis&#227;o da amostra em dois grupos de pacientes com e sem EVA, realizou-se o
               teste estat&#237;stico do qui-quadrado, como j&#225; referido anteriormente. O grupo com EVA
               foi composto por 915 indiv&#237;duos e o grupo sem EVA por 1.578 indiv&#237;duos. Foram ent&#227;o
               comparadas as vari&#225;veis relativas &#224;s indica&#231;&#245;es cl&#237;nicas, fatores de risco e
               resultados do eco-Doppler entre os dois grupos.</p>
        <p>Ap&#243;s a an&#225;lise estat&#237;stica e como demonstra a <xref ref-type="table" rid="t06">Tabela
                  3</xref>, destaca-se importante rela&#231;&#227;o significativa com a vari&#225;vel HA (p &lt;
               0,001), com o IAM (p = 0,007), com a fun&#231;&#227;o sist&#243;lica esquerda alterada (p &lt;
               0,001) e com a mobilidade segmentar alterada (p &lt; 0,001). Por outro lado, n&#227;o se
               verificou rela&#231;&#227;o significativa com a hipercolesterolemia, AVC e tabagismo. Tamb&#233;m
               n&#227;o se registrou uma rela&#231;&#227;o significativa com g&#234;nero, sendo que o g&#234;nero masculino
               apresentou uma preval&#234;ncia de EVA de 17,3% e o g&#234;nero feminino de 19,4%.</p>
        <table-wrap id="t06">
          <label>Tabela 3</label>
          <caption>
            <title>Resultados dos testes estat&#237;sticos de compara&#231;&#227;o de vari&#225;veis entre os dois
                     grupos (n = 2.493)</title>
          </caption>
          <table frame="hsides" rules="rows">
            <thead>
              <tr>
                <th colspan="2" rowspan="2" align="left">Vari&#225;vel</th>
                <th align="center" style="border-bottom:hidden">Grupo com EVA (n = 915)</th>
                <th align="center" style="border-bottom:hidden">Grupo sem EVA (n =
                           1.578)</th>
                <th rowspan="2" align="center">Valor de p</th>
              </tr>
              <tr>
                <th align="center">%/(N)</th>
                <th align="center">%(N)</th>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td rowspan="4" align="left">Indica&#231;&#227;o Cl&#237;nica</td>
                <td align="center">Insufici&#234;ncia Card&#237;aca</td>
                <td align="center">15% (137)</td>
                <td align="center">12,2% (192)</td>
                <td align="center">0,046</td>
              </tr>
              <tr>
                <td align="center">AVC</td>
                <td align="center">30,7% (281)</td>
                <td align="center">27,6% (436)</td>
                <td align="center">0,101</td>
              </tr>
              <tr>
                <td align="center">Doen&#231;a Pulmonar</td>
                <td align="center">14,5% (133)</td>
                <td align="center">15,8% (250)</td>
                <td align="center">0,383</td>
              </tr>
              <tr>
                <td align="center">IAM</td>
                <td align="center">10,1% (92)</td>
                <td align="center">7% (110)</td>
                <td align="center">0,007</td>
              </tr>
              <tr>
                <td rowspan="5" align="left">Fatores de Risco</td>
                <td align="center">HA</td>
                <td align="center">68,5% (627)</td>
                <td align="center">56,3% (888)</td>
                <td align="center">&lt; 0,001</td>
              </tr>
              <tr>
                <td align="center">Hipercolesterolemia</td>
                <td align="center">27,3% (250)</td>
                <td align="center">26,8% (423)</td>
                <td align="center">0,780</td>
              </tr>
              <tr>
                <td align="center">DM</td>
                <td align="center">23% (210)</td>
                <td align="center">18,4% (290)</td>
                <td align="center">0,006</td>
              </tr>
              <tr>
                <td align="center">Tabagismo</td>
                <td align="center">3,1% (28)</td>
                <td align="center">5,8% (92)</td>
                <td align="center">0,002</td>
              </tr>
              <tr>
                <td align="center">Fibrila&#231;&#227;o Atrial</td>
                <td align="center">11% (101)</td>
                <td align="center">12,8% (202)</td>
                <td align="center">0,194</td>
              </tr>
              <tr>
                <td rowspan="3" align="left">Resultados Patol&#243;gicos de Eco-Doppler
                           Card&#237;aco</td>
                <td align="center">FSVE alterada</td>
                <td align="center">9,5% (87)</td>
                <td align="center">0,1% (1)</td>
                <td align="center">&lt; 0,001</td>
              </tr>
              <tr>
                <td align="center">DC dilatadas</td>
                <td align="center">1,9% (17)</td>
                <td align="center">11,8% (186)</td>
                <td align="center">&lt; 0,001</td>
              </tr>
              <tr>
                <td align="center">EVM</td>
                <td align="center">45,6% (404)</td>
                <td align="center">32,3% (510)</td>
                <td align="center">&lt; 0,001</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN01t06">
              <p>EVA: Esclerose valvar a&#243;rtica; AVC: Acidente vascular cerebral; IAM: Infarto
                        agudo do mioc&#225;rdio; HA: Hipertens&#227;o arterial; DM: Diabetes mellitus; FSVE:
                        Fun&#231;&#227;o sist&#243;lica ventricular esquerda; DC: Dimens&#245;es cavit&#225;rias esquerdas;
                        EVM: Esclerose valvar mitral.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
        <p>Verifica-se assim uma rela&#231;&#227;o significativa entre a presen&#231;a de IAM, HA, DM e fun&#231;&#227;o
               sist&#243;lica ventricular esquerda alterada nos pacientes com EVA em compara&#231;&#227;o aos
               pacientes sem EVA .</p>
        <p>A EVA pode ser utilizada como marcador de risco para a doen&#231;a coronariana, como
               demostrado j&#225; em diversos estudos. Apesar do seu mecanismo bioqu&#237;mico ainda n&#227;o ser
               totalmente claro, esta rela&#231;&#227;o j&#225; &#233; amplamente conhecida. Considera-se que os
               processos inflamat&#243;rio e degenerativo envolvidos na EVA afetem os vasos coron&#225;rios
               adjacentes a este sistema valvular e ataquem a parede das art&#233;rias, agravando
               processos ateroscler&#243;ticos pr&#233;-existentes<xref ref-type="bibr" rid="B01">1</xref><sup>-</sup><xref ref-type="bibr" rid="B03">3</xref><sup>,</sup><xref ref-type="bibr" rid="B06">6</xref>.</p>
      </sec>
      <sec sec-type="discussion">
        <title>Discuss&#227;o</title>
        <p>Na amostra estudada, pudemos observar que existe um equil&#237;brio entre a preval&#234;ncia de
               EVA entre os g&#234;neros masculino e feminino (17,3% / 19,4%) o que vai de encontro a
               outros estudos realizados. Observa-se ainda uma m&#233;dia de idade avan&#231;ada (67,5 anos),
               verificando-se que a EVA, como patologia degenerativa, afeta principalmente as
               classes et&#225;rias superiores<xref ref-type="bibr" rid="B10">10</xref>.</p>
        <p>Em rela&#231;&#227;o aos valores das preval&#234;ncias obtidas neste estudo e comparando-os com
               outros artigos cient&#237;ficos de refer&#234;ncia no estudo de EVA, destaca-se uma preval&#234;ncia
               de AVC relevante em quase um ter&#231;o da amostra (28,8%) apresentando um resultado bem
               mais elevado em compara&#231;&#227;o ao estudo de Otto e cols.(1999) no qual a preval&#234;ncia de
               AVC entre indiv&#237;duos com EVA foi de 8%. Apesar da discrep&#226;ncia de valores, n&#227;o foi
               encontrada signific&#226;ncia neste estudo (p = 0,101) ao contr&#225;rio do estudo de Otto e
                  cols<xref ref-type="bibr" rid="B11">11</xref>. (p = 0,003). Ainda no mesmo estudo,
               foi encontrada uma preval&#234;ncia de IAM de 8,6%, valor praticamente id&#234;ntico ao nosso
               estudo no qual a preval&#234;ncia de IAM foi de 8,2%, registrando-se em ambos os estudos
               signific&#226;ncia estat&#237;stica em rela&#231;&#227;o ao grupo controle. Como j&#225; referido, o processo
               escler&#243;tico que ocorre na valva a&#243;rtica &#233; similar ao processo ateroscler&#243;tico pelo
               qual o agravamento na degenera&#231;&#227;o a&#243;rtica pode acelerar o desenvolvimento das placas
               ateromatosas das art&#233;rias coron&#225;rias que se encontram na periferia do sistema
               valvular, levando assim ao aparecimento de sintomatologia associada &#224; DAC<xref ref-type="bibr" rid="B06">6</xref><sup>,</sup><xref ref-type="bibr" rid="B11">11</xref>.</p>
        <p>Nas preval&#234;ncias relativas aos fatores de risco, a HA apresentou um valor de 60,8%,
               ligeiramente inferior a 69%, encontrado por Hsu e cols.<xref ref-type="bibr" rid="B07">7</xref>, mas superior ao de 51,7% encontrado por Otto e cols.<xref ref-type="bibr" rid="B11">11</xref>. Em rela&#231;&#227;o &#224;s signific&#226;ncias estat&#237;sticas
               entre o grupo com e sem EVA, Hsu e cols.<xref ref-type="bibr" rid="B07">7</xref> n&#227;o
               registraram rela&#231;&#227;o significativa nesta vari&#225;vel, ao contr&#225;rio do verificado neste
               estudo (p &lt; 0,001) e no estudo de Otto e cols.<xref ref-type="bibr" rid="B11">11</xref>. A influ&#234;ncia da HA no desenvolvimento de EVA explica-se pelo fato da
               valva a&#243;rtica em pacientes com HA estar sujeita a um stress maior devido &#224; press&#227;o
               elevada exercida sobre os folhetos a&#243;rticos, provocando dano no endot&#233;lio dos
               folhetos, &#224; semelhan&#231;a do que ocorre nas les&#245;es ateroscler&#243;ticas<xref ref-type="bibr" rid="B03">3</xref><sup>,</sup><xref ref-type="bibr" rid="B12">12</xref>.</p>
        <p>A preval&#234;ncia registrada de hipercolesterolemia foi de 27%, bastante inferior aos 45%
               observados no estudo de Hsu e cols.<xref ref-type="bibr" rid="B07">7</xref>. Em ambos
               os estudos, n&#227;o foi registrada signific&#226;ncia estat&#237;stica nesta vari&#225;vel. Comparando
               ao estudo realizado por Otto e cols.<xref ref-type="bibr" rid="B11">11</xref>, a
               preval&#234;ncia de DM foi de 13,1%, sem diferen&#231;a estat&#237;stica em rela&#231;&#227;o ao grupo
               controle (p = 0,9), enquanto o valor apurado neste estudo foi de 20,1% obtendo-se uma
               forte signific&#226;ncia estat&#237;stica em rela&#231;&#227;o ao grupo controle (p = 0,006). A falta de
               signific&#226;ncia da hipercolesterolemia foi uma surpresa, uma vez que a presen&#231;a de
               colesterol &#233; um fator importante no processo degenerativo valvular. Isto pode ter
               ocorrido devido ao fato de n&#227;o existir tecido muscular nas valvas a&#243;rticas e da
               deposi&#231;&#227;o de colesterol se dar de forma diferente em rela&#231;&#227;o &#224;s art&#233;rias coron&#225;rias.
               A aus&#234;ncia desta signific&#226;ncia pode ainda ser explicada pelo baixo n&#250;mero de
               diagn&#243;sticos realizados na popula&#231;&#227;o da amostra<xref ref-type="bibr" rid="B13">13</xref><sup>,</sup><xref ref-type="bibr" rid="B14">14</xref>.</p>
        <p>Nos resultados patol&#243;gicos encontrados por eco-Doppler card&#237;aco, a fun&#231;&#227;o sist&#243;lica
               ventricular esquerda alterada apresentou uma preval&#234;ncia de 9,5%, inferior ao estudo
               de Rosa e cols.<xref ref-type="bibr" rid="B10">10</xref> que registraram uma
               preval&#234;ncia de 17,2% com uma forte signific&#226;ncia estat&#237;stica nos dois estudos (p &lt;
               0,001).</p>
        <p>Apesar de n&#227;o existirem estudos que relacionem a EVA com a EVM, esta &#250;ltima teve uma
               preval&#234;ncia de 37,1% com uma forte signific&#226;ncia estat&#237;stica. Uma vez que os tecidos
               org&#226;nicos que formam a valva a&#243;rtica s&#227;o similares aos da valva mitral, &#233; de se
               esperar que os processos que levem ao desenvolvimento de esclerose possam ocorrer em
               ambas as valvas, apesar das suas repercuss&#245;es na doen&#231;a coron&#225;ria poderem ser
               diferentes devido &#224; sua situa&#231;&#227;o anat&#244;mica<xref ref-type="bibr" rid="B15">15
                  </xref><sup>-</sup><xref ref-type="bibr" rid="B17">17</xref>.</p>
        <p>Finalmente, obteve-se uma preval&#234;ncia de EVA de 36,7%, valor superior ao de 25%
               verificado por Rosa e cols.<xref ref-type="bibr" rid="B10">10</xref></p>
        <p>Com base nos dados acima apresentados de compara&#231;&#227;o entre v&#225;rios estudos de
               refer&#234;ncia, nota-se que &#224; exce&#231;&#227;o da hipercolesterolemia, HA e fun&#231;&#227;o sist&#243;lica
               ventricular esquerda alterada, os valores de preval&#234;ncia encontrados neste artigo s&#227;o
               superiores, refor&#231;ando a liga&#231;&#227;o que existe entre a EVA com DM, IAM e AVC.</p>
        <p>Estes resultados sugerem que os pacientes com EVA t&#234;m uma maior tend&#234;ncia a
               desenvolver estes estados cl&#237;nicos. A atua&#231;&#227;o m&#233;dica deve incidir especialmente
               nestes pacientes no sentido de refor&#231;ar as terap&#234;uticas e melhorar as medidas para
               prevenir os fatores de risco.</p>
      </sec>
      <sec sec-type="conclusions">
        <title>Conclus&#227;o</title>
        <p>Conclui-se assim, que existe uma associa&#231;&#227;o entre a presen&#231;a de EVA e a ocorr&#234;ncia
               pr&#233;via de IAM, DM e fun&#231;&#227;o sist&#243;lica ventricular esquerda alterada. Confirma-se assim
               a hip&#243;tese principal deste estudo em rela&#231;&#227;o &#224; associa&#231;&#227;o entre a presen&#231;a pr&#233;via de
               DAC e EVA, &#224; semelhan&#231;a dos principais estudos neste tema. Esta associa&#231;&#227;o pode levar
               a uma valoriza&#231;&#227;o da presen&#231;a da EVA nos exames de ultrassonografia, que pode ser
               considerada como um marcador de risco para a suspeita de DAC<xref ref-type="bibr" rid="B06">6</xref><sup>,</sup><xref ref-type="bibr" rid="B18">18</xref>.</p>
        <p>Uma limita&#231;&#227;o do estudo &#233; o fato da amostra ter sido selecionada em um laborat&#243;rio
               que presta assist&#234;ncia sobretudo &#224; unidade de AVC e internamento de medicina interna,
               o que pode ter influenciado a preval&#234;ncia de AVC. Outra limita&#231;&#227;o do estudo refere-se
               &#224; aus&#234;ncia de an&#225;lise estat&#237;stica multivariada que n&#227;o apresentou resultados
               significativos.</p>
        <p>Como sugest&#227;o para estudos futuros, prop&#245;em-se investigar se &#224; semelhan&#231;a da EVA,
               tamb&#233;m a EVM poderia influenciar a ocorr&#234;ncia de IAM e se poderia ou n&#227;o existir
               influ&#234;ncia na ocorr&#234;ncia de AVC. A equipe de investiga&#231;&#227;o sugere ainda que poderia
               ser vantajosa a realiza&#231;&#227;o de um estudo longitudinal sobre este tema.</p>
      </sec>
    </body>
    <back>
      <fn-group>
        <fn fn-type="con">
          <p>
            <bold>Contribui&#231;&#227;o dos autores</bold>
          </p>
          <p>Concep&#231;&#227;o e desenho da pesquisa, An&#225;lise e interpreta&#231;&#227;o dos dados, An&#225;lise
                  estat&#237;stica e Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do intelectual
                  importante: Marmelo FC, Mateus SMF, Pereira AJM; Obten&#231;&#227;o de dados e Obten&#231;&#227;o de
                  financiamento: Marmelo FC, Mateus SMF; Reda&#231;&#227;o do manuscrito: Marmelo FC.</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>
        <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>Este artigo &#233; parte de Licenciatura de Filipe Carvalho Marmelo pela Escola
                  Superior de Sa&#250;de Dr. Lopes Dias.</p>
        </fn>
      </fn-group>
    </back>
  </sub-article>
</article>
