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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">ZGFTWG5yvFw7WWNsc9V5Nrt</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v2">S0066-782X2015002000099</article-id>
      <article-id pub-id-type="doi">10.5935/abc.20150081</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Letter to the Editor</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Association between Aortic Valve Sclerosis and Adverse Cardiovascular Events</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Lucena</surname>
            <given-names>Cristiane Machado</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
          <xref ref-type="corresp" rid="c01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Santos</surname>
            <given-names>Rodrigo Pires dos</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
      </contrib-group>
      <aff id="aff01">
        <institution content-type="orgname">Funda&#231;&#227;o Universit&#225;ria de Cardiologia</institution>
        <addr-line>
          <named-content content-type="city">Porto Alegre</named-content>
          <named-content content-type="state">RS</named-content>
        </addr-line>
        <country country="BR">Brazil</country>
        <institution content-type="original">Funda&#231;&#227;o Universit&#225;ria de Cardiologia, Santana, Porto Alegre, RS - Brazil</institution>
      </aff>
      <author-notes>
        <corresp id="c01"><bold>Mailing Address: Cristiane Machado Lucena</bold>, Av. Princesa Isabel, 370 - 3&#186; andar, Santana. Postal Code 90620-000, Porto Alegre, RS - Brazil E-mail: <email>crismluc@gmail.com</email>; <email>crismls@ig.com.br</email>
				</corresp>
      </author-notes>
      <pub-date pub-type="epub-ppub">
        <month>07</month>
        <year>2015</year>
      </pub-date>
      <volume>105</volume>
      <issue>01</issue>
      <fpage>99</fpage>
      <lpage>100</lpage>
      <history>
        <date date-type="received">
          <day>31</day>
          <month>01</month>
          <year>2015</year>
        </date>
        <date date-type="rev-recd">
          <day>11</day>
          <month>03</month>
          <year>2015</year>
        </date>
        <date date-type="accepted">
          <day>17</day>
          <month>03</month>
          <year>2015</year>
        </date>
      </history>
      <permissions>
        <license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by-nc/4.0/">
          <license-p>This is an Open Access article distributed under the terms of the Creative Commons Attribution NonCommercial License which permits unrestricted noncommercial use, distribution, and reproduction in any medium provided the original work is properly cited.</license-p>
        </license>
      </permissions>
      <kwd-group xml:lang="en">
        <title>Keywords</title>
        <kwd>Heart Valve Diseases/physiopathology</kwd>
        <kwd>Coronary Artery Disease</kwd>
        <kwd>Cardiovascular Risk Factors</kwd>
        <kwd>Doppler Echocardiography</kwd>
      </kwd-group>
      <counts>
        <fig-count count="0"/>
        <table-count count="0"/>
        <equation-count count="0"/>
        <ref-count count="5"/>
        <page-count count="2"/>
      </counts>
    </article-meta>
  </front>
  <body>
    <sec>
      <title>Dear Editor,</title>
      <p>The presence of aortic valve sclerosis (AVS) is associated with adverse cardiovascular events even when pre-existing risk factors are considered. In the Cardiovascular Health Study, which included more than 5,000 patients who were &#8805; 65 years of age and were periodically evaluated for more than five years, AVS was associated with a 40% increase in the risk of myocardial infarction; in patients who did not initially present with heart disease, there were a trend toward an increased risk of angina, heart failure, and stroke. It is still unclear whether the mechanism of association between AVS and adverse clinical cardiovascular events is caused by diffuse atherosclerosis, endothelial dysfunction, altered calcium metabolism, lipid accumulation, genetic polymorphism, or other as yet undefined factors<xref ref-type="bibr" rid="B01">1</xref>.</p>
      <p>AVS is defined as thickening and increased echogenicity in the aortic leaflets with no reduction in mobility on an echocardiograph<xref ref-type="bibr" rid="B02">2</xref>. The early lesion of AVS is an active process with some similarities to atherosclerosis, including the histopathological features and an association with risk for coronary artery disease. Patients are at greater risk for coronary artery disease if they are older, male, hypertensive, smokers, diabetics, or if their HDL and LDL levels are high<xref ref-type="bibr" rid="B01">1</xref>. A cross-sectional study by Marmelo et al.<xref ref-type="bibr" rid="B02">2</xref> evaluated 2,494 individuals who presented with AVS diagnosed via transthoracic Doppler echocardiography. These individuals also had a greater prevalence of hypertension, previous myocardial infarction, diabetes, a history of smoking, left ventricular systolic dysfunction, and mitral valve sclerosis. Multivariate analysis allows for a more complete study of the association between each variable and its outcome.</p>
    </sec>
  </body>
  <back>
    <ref-list>
      <title>References</title>
      <ref id="B01">
        <label>1</label>
        <mixed-citation>Otto CM. Why is aortic sclerosis associated with adverse clinical outcomes? J Am Coll Cardiol. 2004;43(2):176-8.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Otto</surname>
              <given-names>CM</given-names>
            </name>
          </person-group>
          <article-title>Why is aortic sclerosis associated with adverse clinical outcomes</article-title>
          <source>J Am Coll Cardiol</source>
          <year>2004</year>
          <volume>43</volume>
          <issue>2</issue>
          <fpage>176</fpage>
          <lpage>178</lpage>
        </element-citation>
      </ref>
      <ref id="B02">
        <label>2</label>
        <mixed-citation>Marmelo FC, Mateus SM, Pereira AJ. Associa&#231;&#227;o entre esclerose valvar a&#243;rtica com doen&#231;a arterial coronariana pr&#233;via e fatores de risco. Arq Bras Cardiol. 2014;103(5):398-402.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Marmelo</surname>
              <given-names>FC</given-names>
            </name>
            <name>
              <surname>Mateus</surname>
              <given-names>SM</given-names>
            </name>
            <name>
              <surname>Pereira</surname>
              <given-names>AJ</given-names>
            </name>
          </person-group>
          <article-title>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>
          <source>Arq Bras Cardiol</source>
          <year>2014</year>
          <volume>103</volume>
          <issue>5</issue>
          <fpage>398</fpage>
          <lpage>402</lpage>
        </element-citation>
      </ref>
    </ref-list>
  </back>
  <sub-article article-type="reply" id="SA1" xml:lang="en">
    <front-stub>
      <title-group>
        <article-title>Replay</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Marmelo</surname>
            <given-names>Felipe C.</given-names>
          </name>
        </contrib>
      </contrib-group>
    </front-stub>
    <body>
      <p>As established in international guidelines, aortic valve sclerosis (AVS) is defined as an increased thickness and hardening of the aortic leaflets with no commissural fusion   <xref ref-type="bibr" rid="B03">1</xref>.</p>
      <p>One of the pioneers in the study of aortic sclerosis was Catherine Otto, who conducted several studies on this topic and verified the association between AVS and various adverse cardiovascular events. Her studies are still used as reference in current research regarding the association between AVS and coronary artery disease (CAD)<xref ref-type="bibr" rid="B04">2</xref>.</p>
      <p>Though the mechanism that verifies the association between AVS and the development of CAD is not completely clear, most single- and multi-center international studies support the existence of this association, warn of the dangers of this association, and encourage frequent follow-up once the diagnosis is made. In the study by Conte et al.<xref ref-type="bibr" rid="B05">3</xref>, AVS echocardiograms of patients who reported chest pain were used to predict obstructive coronary disease. This method achieved a sensitivity of 38% and a specificity of 86%; the stress echocardiogram has a sensitivity of 67% and a specificity of 72% for the diagnosis of coronary heart disease. Thus, Conte et al. proved that the mere presence of AVS can be a marker for cardiovascular risk.</p>
      <p>A cross-sectional study by Marmelo et al.<xref ref-type="bibr" rid="B03">1</xref>, which included 2,493 individuals, compared AVS patients and non-AVS patients and verified a significant increase in the association between AVS and hypertension, diabetes, history of smoking, heart failure, left ventricular dysfunction, and acute myocardial infarction. Because this was a cross-sectional study in which the multivariate analysis did not produce significant results, the authors suggested future longitudinal studies with multivariate analyses. This way, greater statistical validation of the association between the variables can be achieved.</p>
      <sig-block>Sincerely,<break/>
				<sig>Felipe C. Marmelo</sig>
			</sig-block>
    </body>
    <back>
      <ref-list>
        <title>References</title>
        <ref id="B03">
          <label>1</label>
          <mixed-citation>Marmelo FC, Mateus SM, Pereira AJ. Associa&#231;&#227;o entre esclerose valvar a&#243;rtica com doen&#231;a arterial coronariana pr&#233;via e fatores de risco. Arq Bras Cardiol. 2014;103(5):398-402.</mixed-citation>
          <element-citation publication-type="journal">
            <person-group person-group-type="author">
              <name>
                <surname>Marmelo</surname>
                <given-names>FC</given-names>
              </name>
              <name>
                <surname>Mateus</surname>
                <given-names>SM</given-names>
              </name>
              <name>
                <surname>Pereira</surname>
                <given-names>AJ</given-names>
              </name>
            </person-group>
            <article-title>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>
            <source>J Am Coll Cardiol</source>
            <year>2014</year>
            <volume>103</volume>
            <issue>5</issue>
            <fpage>398</fpage>
            <lpage>402</lpage>
          </element-citation>
        </ref>
        <ref id="B04">
          <label>2</label>
          <mixed-citation>Otto CM, Lind BK, Kitzman DW, Gersh BJ, Siscovick DS. Association of aortic-valve sclerosis with cardiovascular mortality and morbidity in the elderly. N Eng J Med. 1999;341(13):142-7.</mixed-citation>
          <element-citation publication-type="journal">
            <person-group person-group-type="author">
              <name>
                <surname>Otto</surname>
                <given-names>CM</given-names>
              </name>
              <name>
                <surname>Lind</surname>
                <given-names>BK</given-names>
              </name>
              <name>
                <surname>Kitzman</surname>
                <given-names>DW</given-names>
              </name>
              <name>
                <surname>Gersh</surname>
                <given-names>BJ</given-names>
              </name>
              <name>
                <surname>Siscovick</surname>
                <given-names>DS</given-names>
              </name>
            </person-group>
            <article-title>Association of aortic-valve sclerosis with cardiovascular mortality and morbidity in the elderly</article-title>
            <source>N Eng J Med</source>
            <year>1999</year>
            <volume>341</volume>
            <issue>13</issue>
            <fpage>142</fpage>
            <lpage>147</lpage>
          </element-citation>
        </ref>
        <ref id="B05">
          <label>3</label>
          <mixed-citation>Conte L, Rossi A, Cicoira M, Bonapace S, Amado EA, Golia G, et al. Aortic valve sclerosis: a marker of significant obstructive coronary artery disease in patients with chest pain? J Am Soc Echocardiogr. 2007;20(6):703-8.</mixed-citation>
          <element-citation publication-type="journal">
            <person-group person-group-type="author">
              <name>
                <surname>Conte</surname>
                <given-names>L</given-names>
              </name>
              <name>
                <surname>Rossi</surname>
                <given-names>A</given-names>
              </name>
              <name>
                <surname>Cicoira</surname>
                <given-names>M</given-names>
              </name>
              <name>
                <surname>S</surname>
                <given-names>Bonapace</given-names>
              </name>
              <name>
                <surname>Amado</surname>
                <given-names>EA</given-names>
              </name>
              <name>
                <surname>Golia</surname>
                <given-names>G</given-names>
              </name>
              <etal/>
            </person-group>
            <article-title>Aortic valve sclerosis: a marker of significant obstructive coronary artery disease in patients with chest pain?</article-title>
            <source>J Am Soc Echocardiogr</source>
            <year>2007</year>
            <volume>20</volume>
            <issue>6</issue>
            <fpage>703</fpage>
            <lpage>708</lpage>
          </element-citation>
        </ref>
      </ref-list>
    </back>
  </sub-article>
  <sub-article article-type="translation" id="SA2" xml:lang="pt">
    <front-stub>
      <title-group>
        <article-title>Associa&#231;&#227;o entre Esclerose Valvar A&#243;rtica e Eventos Cardiovasculares Adversos</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Lucena</surname>
            <given-names>Cristiane Machado</given-names>
          </name>
          <xref ref-type="aff" rid="aff02"/>
          <xref ref-type="corresp" rid="c02"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Santos</surname>
            <given-names>Rodrigo Pires dos</given-names>
          </name>
          <xref ref-type="aff" rid="aff02"/>
        </contrib>
      </contrib-group>
      <aff id="aff02">
        <institution content-type="original">Funda&#231;&#227;o Universit&#225;ria de Cardiologia, Santana, Porto Alegre, RS - Brasil</institution>
      </aff>
      <author-notes>
        <corresp id="c02"><bold>Correspond&#234;ncia: Cristiane Machado Lucena</bold>, Av. Princesa Isabel, 370 - 3&#186; andar, Santana. CEP 90620-000, Porto Alegre, RS - Brasil. E-mail:   <email>crismluc@gmail.com</email>; <email>crismls@ig.com.br</email>
				</corresp>
      </author-notes>
      <kwd-group xml:lang="pt">
        <title>Palavras-chave:</title>
        <kwd>Doen&#231;as das valvas card&#237;acas/fisiopatologia</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>
        <title>Ao Editor</title>
        <p>A presen&#231;a de esclerose valvar a&#243;rtica (EVA) est&#225; associada com eventos cardiovasculares adversos, mesmo quando se leva em conta a presen&#231;a de outros fatores de risco pr&#233;vios. No <italic>Cardiovascular Health Study</italic> realizado com mais de 5.000 indiv&#237;duos de 65 anos ou mais, seguidos por cerca de 5 anos, a EVA esteve associada com um aumento de 40% no risco de infarto do mioc&#225;rdio e com uma tend&#234;ncia de risco aumentado para angina, insufici&#234;ncia card&#237;aca e acidente vascular cerebral nos pacientes sem doen&#231;a cardiovascular inicialmente. Permanece incerto se o mecanismo da associa&#231;&#227;o entre EVA e evolu&#231;&#227;o cl&#237;nica cardiovascular adversa &#233; por aterosclerose difusa, disfun&#231;&#227;o endotelial, metabolismo alterado do c&#225;lcio, ac&#250;mulo lip&#237;dico, polimorfismo gen&#233;tico ou por outros fatores ainda n&#227;o definidos<xref ref-type="bibr" rid="B01">1</xref>.</p>
        <p>A EVA &#233; caracterizada ao ecocardiograma pelo espessamento e aumento da ecogenicidade dos folhetos a&#243;rticos, sem restri&#231;&#227;o na mobilidade<xref ref-type="bibr" rid="B02">2</xref>. A les&#227;o precoce da EVA &#233; um processo ativo com algumas semelhan&#231;as &#224; aterosclerose, incluindo aspectos histopatol&#243;gicos e associa&#231;&#227;o a fatores de risco para doen&#231;a coronariana ateroscler&#243;tica, como idade, sexo masculino, hipertens&#227;o arterial sist&#234;mica, n&#237;veis elevados de lipoprote&#237;na de baixa densidade-colesterol e lipoprote&#237;na(a), fumo e diabetes<xref ref-type="bibr" rid="B01">1</xref>. No estudo transversal de Marmelo e cols.<xref ref-type="bibr" rid="B02">2</xref>, que avaliou 2.493 indiv&#237;duos que apresentavam EVA ao ecodopplercardiograma transtor&#225;cico, foi encontrada maior preval&#234;ncia de hipertens&#227;o arterial sist&#234;mica, infarto do mioc&#225;rdio pr&#233;vio, diabetes, tabagismo, disfun&#231;&#227;o sist&#243;lica ventricular esquerda e esclerose valvar mitral. A utiliza&#231;&#227;o de uma an&#225;lise multivariada permitiria uma explora&#231;&#227;o mais adequada da associa&#231;&#227;o entre cada vari&#225;vel com o desfecho.</p>
      </sec>
    </body>
  </sub-article>
  <sub-article article-type="translation" id="SA3" xml:lang="pt">
    <front-stub>
      <title-group>
        <article-title>Carta-resposta</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Marmelo</surname>
            <given-names>Felipe C.</given-names>
          </name>
        </contrib>
      </contrib-group>
    </front-stub>
    <body>
      <p>Como estabelecido em <italic>guidelines  </italic>internacionais, a esclerose valvar a&#243;rtica (EVA) define-se como um aumento da espessura dos folhetos a&#243;rticos, bem como seu endurecimento, sem que haja fus&#227;o das comissuras<xref ref-type="bibr" rid="B03">1</xref>.</p>
      <p>Uma das grandes pioneiras do estudo da esclerose a&#243;rtica foi Catherine Otto, que desenvolveu v&#225;rios estudos sobre essa tem&#225;tica, e verificou uma liga&#231;&#227;o entre EVA e a ocorr&#234;ncia de diversos eventos cardiovasculares adversos. Ainda nas investiga&#231;&#245;es de hoje sobre a associa&#231;&#227;o de EVA com doen&#231;a arterial coron&#225;ria (DAC), seus estudos s&#227;o considerados refer&#234;ncia<xref ref-type="bibr" rid="B04">2</xref>.</p>
      <p>Apesar do mecanismo que leva &#224; verifica&#231;&#227;o de uma associa&#231;&#227;o entre a EVA e o desenvolvimento de DAC n&#227;o ser ainda totalmente claro, a maioria dos estudos internacionais, sejam eles unic&#234;ntricos ou multic&#234;ntricos, apoia a exist&#234;ncia da dita associa&#231;&#227;o, alertando que esta deve ser considerada s&#233;ria, devendo existir, desde do momento inicial do diagn&#243;stico, um acompanhamento apertado da sua evolu&#231;&#227;o. No estudo de Conte e cols.<xref ref-type="bibr" rid="B05">3</xref>, foi utilizado o achado ecocardiogr&#225;fico de EVA em pacientes com dor precordial, para prever a exist&#234;ncia de doen&#231;a coron&#225;ria obstrutiva. Esse m&#233;todo obteve sensibilidade de 38% e especificidade de 86%, sendo que o eletrocardiograma em prova de esfor&#231;o tem uma sensibilidade de 67% e uma especificidade de 72% para o diagn&#243;stico de doen&#231;a coron&#225;ria. Assim, Conti e cols. provaram que a simples presen&#231;a de EVA pode ser utilizada como marcador de risco cardiovascular.</p>
      <p>Relativamente ao estudo transversal de Marmelo e cols.<xref ref-type="bibr" rid="B03">1</xref>, realizado com 2.493 indiv&#237;duos, verificou-se, como na maioria dos estudos, um aumento significativo da preval&#234;ncia de hipertens&#227;o arterial, diabetes, tabagismo, insufici&#234;ncia card&#237;aca, fun&#231;&#227;o ventricular esquerda alterada e infarto agudo do mioc&#225;rdio nos pacientes com EVA em compara&#231;&#227;o aos pacientes sem EVA. Sendo este um estudo transversal, cuja an&#225;lise multivariada n&#227;o produziu resultados significativos, os autores sugerem como poss&#237;vel estudo futuro a realiza&#231;&#227;o de um estudo longitudinal com an&#225;lise multivariada, permitindo, assim, uma maior valida&#231;&#227;o estat&#237;stica entre as vari&#225;veis da associa&#231;&#227;o encontrada.</p>
      <sig-block>Atenciosamente,<break/>
				<sig>Felipe C. Marmelo</sig>
			</sig-block>
    </body>
  </sub-article>
</article>
