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  <front>
    <journal-meta>
      <journal-id journal-id-type="nlm-ta">Arq Bras Cardiol</journal-id>
      <journal-id journal-id-type="publisher-id">abc</journal-id>
      <journal-title-group>
        <journal-title>Arquivos Brasileiros de Cardiologia</journal-title>
        <abbrev-journal-title abbrev-type="publisher">Arq. Bras. Cardiol.</abbrev-journal-title>
      </journal-title-group>
      <issn pub-type="ppub">0066-782X</issn>
      <issn pub-type="epub">1678-4170</issn>
      <publisher>
        <publisher-name>Sociedade Brasileira de Cardiologia - SBC</publisher-name>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id specific-use="scielo-v3" pub-id-type="publisher-id">SDZ35yMKf5h73kTHMBXBpyb</article-id>
      <article-id specific-use="scielo-v2" pub-id-type="publisher-id">S0066-782X2024000100901</article-id>
      <article-id pub-id-type="other">00901</article-id>
      <article-id pub-id-type="doi">10.36660/abc.20230691</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Carta ao Editor</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>A Rela&#231;&#227;o entre a Raz&#227;o &#193;cido &#218;rico/Albumina e a Espessura M&#233;dia-Intimal da Car&#243;tida em Pacientes com Hipertens&#227;o</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-9830-0161</contrib-id>
          <name>
            <surname>Nascimento</surname>
            <given-names>Cristian Rodrigues do</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Ribeiro</surname>
            <given-names>Jo&#227;o Luis Matos</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0001-5712-2111</contrib-id>
          <name>
            <surname>Mendes</surname>
            <given-names>Rodrigo</given-names>
          </name>
          <xref ref-type="aff" rid="aff2">
            <sup>2</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Barbosa</surname>
            <given-names>Romero Henrique de Almeida</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Lopes</surname>
            <given-names>Johnnatas Mikael</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0003-1032-6015</contrib-id>
          <name>
            <surname>Ten&#243;rio</surname>
            <given-names>Pedro Pereira</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
          <xref ref-type="corresp" rid="c1"/>
        </contrib>
        <aff id="aff1">
          <label>1</label>
          <institution content-type="orgname">Universidade Federal do Vale do Sa&#227;o Francisco</institution>
          <institution content-type="orgdiv1">Colegiado de Medicina</institution>
          <addr-line>
            <named-content content-type="city">Paulo Afonso</named-content>
            <named-content content-type="state">BA</named-content>
          </addr-line>
          <country country="BR">Brasil</country>
          <institution content-type="original">Universidade Federal do Vale do Sa&#227;o Francisco &#8211; Colegiado de Medicina, Paulo Afonso, BA &#8211; Brasil</institution>
        </aff>
        <aff id="aff2">
          <label>2</label>
          <institution content-type="orgname">Irmandade Santa Casa de Miseric&#243;rdia de S&#227;o Paulo</institution>
          <addr-line>
            <named-content content-type="city">S&#227;o Paulo</named-content>
            <named-content content-type="state">SP</named-content>
          </addr-line>
          <country country="BR">Brasil</country>
          <institution content-type="original">Irmandade Santa Casa de Miseric&#243;rdia de S&#227;o Paulo, S&#227;o Paulo, SP &#8211; Brasil</institution>
        </aff>
      </contrib-group>
      <author-notes>
        <corresp id="c1"><bold>Correspond&#234;ncia: Pedro Pereira Ten&#243;rio</bold> &#8226; Avenida da Amizade, 1900. CEP <postal-code>48605-780</postal-code>, Bairro Sal Torrado, Paulo Afonso, BA &#8211; Brasil E-mail: <email>pedrotenorio28@gmail.com</email></corresp>
      </author-notes>
      <pub-date publication-format="electronic" date-type="pub">
        <day>08</day>
        <month>03</month>
        <year>2024</year>
      </pub-date>
      <pub-date publication-format="electronic" date-type="collection">
        <year>2024</year>
      </pub-date>
      <volume>121</volume>
      <issue>1</issue>
      <elocation-id>e20230691</elocation-id>
      <history>
        <date date-type="received">
          <day>05</day>
          <month>10</month>
          <year>2023</year>
        </date>
        <date date-type="rev-recd">
          <day>01</day>
          <month>11</month>
          <year>2023</year>
        </date>
        <date date-type="accepted">
          <day>01</day>
          <month>11</month>
          <year>2023</year>
        </date>
      </history>
      <permissions>
        <license license-type="open-access" xml:lang="en" xlink:href="https://creativecommons.org/licenses/by/4.0/">
          <license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution License</license-p>
        </license>
      </permissions>
      <kwd-group xml:lang="pt">
        <title>Palavras-chave</title>
        <kwd>Doen&#231;as Cardiovasculares/complica&#231;&#245;es</kwd>
        <kwd>&#193;cido &#218;rico</kwd>
        <kwd>Albumina S&#233;rica Humana</kwd>
        <kwd>Espessura Intima-M&#233;dia Carot&#237;dea</kwd>
        <kwd>Hipertens&#227;o</kwd>
      </kwd-group>
      <counts>
        <fig-count count="0"/>
        <table-count count="0"/>
        <equation-count count="0"/>
        <ref-count count="21"/>
      </counts>
    </article-meta>
  </front>
  <body>
    <p><bold>Ao Editor</bold>,</p>
    <p>Lemos, atentamente, o artigo intitulado: <italic>"A rela&#231;&#227;o entre a raz&#227;o &#225;cido &#250;rico/albumina e a espessura m&#233;dia-intimal da car&#243;tida em pacientes com hipertens&#227;o"</italic>, cujo objetivo foi investigar a associa&#231;&#227;o da rela&#231;&#227;o &#225;cido &#250;rico/albumina (RUA) e a espessura m&#233;dia-intimal carot&#237;dea (EMIC) em pacientes hipertensos.<sup><xref ref-type="bibr" rid="B1">1</xref></sup> Embora o presente estudo tenha demonstrado uma correla&#231;&#227;o significativa entre RUA e EMIC, com a RUA apresentando maior capacidade discriminativa para valores aumentados de EMIC do que &#225;cido &#250;rico e albumina isolados, e do que os demais marcadores inflamat&#243;rios analisados no estudo, como o &#237;ndice de inflama&#231;&#227;o imune sist&#234;mica (IIS), a raz&#227;o neutr&#243;filo/linf&#243;cito (RNL), a raz&#227;o plaqueta/linf&#243;cito (RPL) e a raz&#227;o prote&#237;na C reativa/albumina (RCA),<sup><xref ref-type="bibr" rid="B1">1</xref></sup> alguns aspectos observados, na leitura do artigo, s&#227;o dignos de nota.</p>
    <p>A classifica&#231;&#227;o dos pacientes em grupos de EMIC aumentada e normal utilizou, como ponto de corte, um valor de 0,9mm, em conson&#226;ncia com o valor de normalidade preconizado nas diretrizes da <italic>European Society of Cardiology</italic> (ESC).<sup><xref ref-type="bibr" rid="B2">2</xref>,<xref ref-type="bibr" rid="B3">3</xref></sup> Essa simplifica&#231;&#227;o, no entanto, pode levar a erros de classifica&#231;&#227;o em diferentes popula&#231;&#245;es e faixas et&#225;rias, nas quais valores semelhantes podem estar dentro da faixa de normalidade.<sup><xref ref-type="bibr" rid="B2">2</xref></sup> Isso foi evidenciado por Homma et al.,<sup><xref ref-type="bibr" rid="B4">4</xref></sup> mediante o achado de que no envelhecimento o aumento da EMIC pode ser decorrente de um processo de espessamento intimal difuso e n&#227;o, necessariamente, da forma&#231;&#227;o de placas ateroscler&#243;ticas. Diante disso, consideramos importante a estratifica&#231;&#227;o da popula&#231;&#227;o estudada por sexo, idade e etnia, tendo em vista a exist&#234;ncia de variabilidade entre esses indiv&#237;duos, o que pode influenciar uma subestima&#231;&#227;o dos resultados.</p>
    <p>No posicionamento de Ultrassonografia Vascular do Departamento de Imagem Cardiovascular da Sociedade Brasileira de Cardiologia &#8211; 2019,<sup><xref ref-type="bibr" rid="B5">5</xref></sup> recomenda-se que ap&#243;s aquisi&#231;&#227;o dos dados num&#233;ricos da EMI, os valores m&#233;dios devem ser comparados com valores de refer&#234;ncia j&#225; existentes, de acordo com as tabelas normativas dos estudos ELSA-Brasil, CAPS ou MESA. A decis&#227;o sobre qual tabela utilizar depender&#225; do g&#234;nero, idade e etnia do indiv&#237;duo. Deve-se acrescentar na conclus&#227;o se a medida se encontra acima ou abaixo do percentil 75, al&#233;m da tabela utilizada com sua refer&#234;ncia bibliogr&#225;fica. Sendo assim, o ponto de corte utilizado na metodologia pode levar a vi&#233;s de confus&#227;o.</p>
    <p>N&#227;o obstante, n&#227;o foi descrito nos grupos a presen&#231;a de placa carot&#237;dea ateromatosa, visto que a identifica&#231;&#227;o da placa &#233; o principal reclassificador de risco cardiovascular. Al&#233;m do mais, a classifica&#231;&#227;o do est&#225;gio da hipertens&#227;o no grupo selecionado, conforme a Diretriz de Hipertens&#227;o Arterial 2020,<sup><xref ref-type="bibr" rid="B6">6</xref></sup> confere um maior risco para les&#227;o de &#243;rg&#227;o alvo quanto mais elevado os n&#237;veis press&#243;ricos, al&#233;m de maiores disfun&#231;&#227;o endotelial e remodelamento vascular arterial.</p>
    <p>Conforme evidenciado na metodologia, foram exclu&#237;dos do estudo pacientes com insufici&#234;ncia card&#237;aca congestiva, hipertens&#227;o secund&#225;ria, doen&#231;a card&#237;aca valvular moderada a grave, doen&#231;a arterial coronariana, doen&#231;a renal ou hep&#225;tica cr&#244;nica, malignidade, infec&#231;&#227;o ativa, doen&#231;a inflamat&#243;ria cr&#244;nica, al&#233;m daqueles que tomavam medicamentos que afetam os n&#237;veis s&#233;ricos de &#225;cido &#250;rico e/ou albumina e aqueles em desnutri&#231;&#227;o.<sup><xref ref-type="bibr" rid="B1">1</xref></sup> No entanto, observamos que indiv&#237;duos acometidos por doen&#231;a arterial obstrutiva perif&#233;rica n&#227;o foram inseridos nos crit&#233;rios de exclus&#227;o da pesquisa, o que pode confundir os resultados apresentados, uma vez que as evid&#234;ncias acerca da correla&#231;&#227;o entre a deteriora&#231;&#227;o ateroscler&#243;tica da parede arterial em territ&#243;rios vasculares perif&#233;ricos e o aumento da EMIC, j&#225; t&#234;m sido demonstradas h&#225; algumas d&#233;cadas.<sup><xref ref-type="bibr" rid="B7">7</xref></sup> Faz-se necess&#225;ria, portanto, a considera&#231;&#227;o dessa comorbidade entre os crit&#233;rios de exclus&#227;o para uma melhor an&#225;lise dos resultados obtidos no estudo.</p>
    <p>Compreendemos, tamb&#233;m, necess&#225;ria a estratifica&#231;&#227;o dos pacientes diab&#233;ticos inclu&#237;dos no estudo em rela&#231;&#227;o &#224; terap&#234;utica antidiab&#233;tica utilizada, tendo em vista o seu potencial de reduzir a EMIC. Tal efeito foi demonstrado, a t&#237;tulo de ilustra&#231;&#227;o, em estudos que analisaram f&#225;rmacos, como liraglutida<sup><xref ref-type="bibr" rid="B8">8</xref></sup> e metformina.<sup><xref ref-type="bibr" rid="B9">9</xref></sup> Devido a esses aspectos, estratificar os indiv&#237;duos em rela&#231;&#227;o ao hipoglicemiante utilizado, ao tempo de tratamento e &#224; dose empregada, desponta como fator relevante para uma melhor interpreta&#231;&#227;o da associa&#231;&#227;o RUA e EMIC.</p>
    <p>Por fim, j&#225; se encontra bem estabelecida a rela&#231;&#227;o entre diabetes <italic>mellitus</italic> e calcifica&#231;&#227;o vascular,<sup><xref ref-type="bibr" rid="B10">10</xref>,<xref ref-type="bibr" rid="B11">11</xref></sup> o que ocorre, entre outros aspectos, pela exposi&#231;&#227;o prolongada das fibras musculares lisas da t&#250;nica m&#233;dia &#224; hiperglicemia.<sup><xref ref-type="bibr" rid="B12">12</xref></sup> Devido a isso, infere-se que o tempo de doen&#231;a apresentado pelos indiv&#237;duos acometidos por diabetes <italic>mellitus</italic> pode ser um preditor desse processo, al&#233;m do que a esclerose calcificante da m&#233;dia pode ser mais um confundidor dos resultados apresentados, justificando, pois, a necessidade de estratificar os pacientes diab&#233;ticos segundo o tempo de doen&#231;a.</p>
  </body>
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  <response response-type="reply" xml:lang="pt" id="R1">
    <front-stub>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Carta-Resposta</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Carta-resposta</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>&#350;ayl&#305;k</surname>
            <given-names>Faysal</given-names>
          </name>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>&#199;&#305;nar</surname>
            <given-names>Tufan</given-names>
          </name>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Selcuk</surname>
            <given-names>Murat</given-names>
          </name>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Tanbo&#287;a</surname>
            <given-names>Ibrahim Halil</given-names>
          </name>
        </contrib>
      </contrib-group>
    </front-stub>
    <body>
      <p><bold>Prezado Editor</bold>,</p>
      <p>Agradecemos aos autores por seus valiosos coment&#225;rios em rela&#231;&#227;o ao nosso estudo intitulado "A rela&#231;&#227;o entre a raz&#227;o &#225;cido &#250;rico/albumina e a espessura m&#233;dio-intimal da car&#243;tida em pacientes com hipertens&#227;o".<sup><xref ref-type="bibr" rid="B13">1</xref></sup></p>
      <p>Concordamos com os autores na quest&#227;o de que a idade est&#225; correlacionada com a espessura m&#233;dio-intimal da car&#243;tida (EMIC), independentemente da forma&#231;&#227;o de placas ateroscler&#243;ticas,<sup><xref ref-type="bibr" rid="B14">2</xref></sup> e o grupo de alta EMIC em nosso estudo era mais velho que o grupo de baixa EMIC. No entanto, eliminamos esse fator de confus&#227;o adicionando essa vari&#225;vel no modelo multivari&#225;vel para obter uma raz&#227;o de chances ajustada para a rela&#231;&#227;o &#225;cido &#250;rico/albumina (RAU) para uma EMIC elevada. Como n&#227;o houve diferen&#231;a entre os grupos quanto ao sexo e tal par&#226;metro tamb&#233;m n&#227;o esteve associado a uma EMIC elevada com base na an&#225;lise de regress&#227;o log&#237;stica univariada, n&#227;o inserimos essa vari&#225;vel no modelo multivari&#225;vel. Finalmente, a popula&#231;&#227;o do nosso estudo consistia apenas de etnia caucasiana branca e n&#227;o havia pacientes de outros grupos &#233;tnicos.</p>
      <p>O valor de corte para discrimina&#231;&#227;o dos grupos de alta e baixa EMIC foi de 0,9 mm, conforme sugerido pelas diretrizes da Sociedade Europeia de Cardiologia.<sup><xref ref-type="bibr" rid="B15">3</xref></sup> Como esse valor de corte tamb&#233;m foi utilizado para determinar os pacientes com alto risco cardiovascular na literatura, aplicamos esse valor de corte em nosso estudo.<sup><xref ref-type="bibr" rid="B16">4</xref></sup></p>
      <p>&#201; uma quest&#227;o bem conhecida que a presen&#231;a de placa ateromatosa &#233; um preditor independente de risco cardiovascular.<sup><xref ref-type="bibr" rid="B17">5</xref></sup> O estudo teve como objetivo avaliar a rela&#231;&#227;o entre a RAU e a CIMT. Assim, n&#227;o investigamos a presen&#231;a de placa de ateroma e seu papel preditivo no risco cardiovascular.</p>
      <p>Concordamos com os autores quanto &#224; rela&#231;&#227;o entre o est&#225;gio da hipertens&#227;o e o risco de danos a &#243;rg&#227;os-alvo, incluindo remodela&#231;&#227;o vascular e disfun&#231;&#227;o endotelial.<sup><xref ref-type="bibr" rid="B18">6</xref></sup> No entanto, a grande maioria dos pacientes j&#225; tinha diagn&#243;stico de hipertens&#227;o antes da inclus&#227;o no estudo e estava em tratamento anti-hipertensivo h&#225; algum tempo. Com o aux&#237;lio de medicamentos anti-hipertensivos, os valores da press&#227;o arterial foram normalizados na maioria dos pacientes. Com isso, a classifica&#231;&#227;o da hipertens&#227;o baseada nas diretrizes recomendadas n&#227;o foi aplic&#225;vel em nosso estudo. Portanto, n&#227;o pudemos avaliar o impacto do grau de hipertens&#227;o na EMIC neste estudo. Conforme mencionado pelos autores, h&#225; fortes evid&#234;ncias de deteriora&#231;&#227;o arterial perif&#233;rica e maior EMIC.<sup><xref ref-type="bibr" rid="B19">7</xref></sup> Assim, exclu&#237;mos do estudo os pacientes com doen&#231;a arterial perif&#233;rica. Por&#233;m, n&#227;o mencionamos isso no crit&#233;rio de exclus&#227;o.</p>
      <p>A frequ&#234;ncia de pacientes com e sem diabetes mellitus (DM) foi semelhante entre os grupos de alta e baixa EMIC em nosso estudo (p-valor = 0,280). Al&#233;m disso, o DM n&#227;o se associou &#224; EMIC elevada na an&#225;lise de regress&#227;o log&#237;stica univariada. Assim, n&#227;o houve impacto do DM em ter uma EMIC elevada em nosso estudo. Al&#233;m disso, pacientes diab&#233;ticos com maior dura&#231;&#227;o da doen&#231;a podem desenvolver complica&#231;&#245;es micro e macrovasculares. Devido ao dif&#237;cil c&#225;lculo da EMIC nesses pacientes, n&#227;o inclu&#237;mos esses pacientes neste estudo. Reconhecemos que os medicamentos antidiab&#233;ticos, incluindo a liraglutida e a metformina, podem ter efeitos na EMIC.<sup><xref ref-type="bibr" rid="B20">8</xref>,<xref ref-type="bibr" rid="B21">9</xref></sup> Por outro lado, inibidores do GLT-1 como a liraglutida t&#234;m sido recentemente utilizados para o tratamento do DM em nosso pa&#237;s. Como descrevemos acima, devido &#224; distribui&#231;&#227;o homog&#234;nea dos pacientes diab&#233;ticos entre os grupos de estudo, n&#227;o consideramos que o DM teve um impacto tendencioso na EMIC neste estudo. Entretanto, n&#227;o coletamos dados referentes &#224; dura&#231;&#227;o do DM, bem como &#224; dosagem e dura&#231;&#227;o dos medicamentos antidiab&#233;ticos. Assim, essas limita&#231;&#245;es podem ser adicionadas na parte de limita&#231;&#245;es do texto.</p>
    </body>
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  <sub-article article-type="translation" id="TRen" xml:lang="en">
    <front-stub>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Letter to the Editor</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>The Relationship between Uric Acid/Albumin Ratio and Carotid Intima-Media Thickness in Patients with Hypertension</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-9830-0161</contrib-id>
          <name>
            <surname>Nascimento</surname>
            <given-names>Cristian Rodrigues do</given-names>
          </name>
          <xref ref-type="aff" rid="aff3">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Ribeiro</surname>
            <given-names>Jo&#227;o Luis Matos</given-names>
          </name>
          <xref ref-type="aff" rid="aff3">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0001-5712-2111</contrib-id>
          <name>
            <surname>Mendes</surname>
            <given-names>Rodrigo</given-names>
          </name>
          <xref ref-type="aff" rid="aff4">
            <sup>2</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Barbosa</surname>
            <given-names>Romero Henrique de Almeida</given-names>
          </name>
          <xref ref-type="aff" rid="aff3">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Lopes</surname>
            <given-names>Johnnatas Mikael</given-names>
          </name>
          <xref ref-type="aff" rid="aff3">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0003-1032-6015</contrib-id>
          <name>
            <surname>Ten&#243;rio</surname>
            <given-names>Pedro Pereira</given-names>
          </name>
          <xref ref-type="aff" rid="aff3">
            <sup>1</sup>
          </xref>
          <xref ref-type="corresp" rid="c2"/>
        </contrib>
        <aff id="aff3">
          <label>1</label>
          <addr-line>
            <named-content content-type="city">Paulo Afonso</named-content>
            <named-content content-type="state">BA</named-content>
          </addr-line>
          <country country="BR">Brazil</country>
          <institution content-type="original">Universidade Federal do Vale do Sa&#227;o Francisco &#8211; Colegiado de Medicina, Paulo Afonso, BA &#8211; Brazil</institution>
        </aff>
        <aff id="aff4">
          <label>2</label>
          <addr-line>
            <named-content content-type="city">S&#227;o Paulo</named-content>
            <named-content content-type="state">SP</named-content>
          </addr-line>
          <country country="BR">Brazil</country>
          <institution content-type="original">Irmandade Santa Casa de Miseric&#243;rdia de S&#227;o Paulo, S&#227;o Paulo, SP &#8211; Brazil</institution>
        </aff>
      </contrib-group>
      <author-notes>
        <corresp id="c2"><bold>Mailing Address: Pedro Pereira Ten&#243;rio</bold> &#8226; Avenida da Amizade, 1900. P <postal-code>48605-780</postal-code>, Bairro Sal Torrado, Paulo Afonso, BA &#8211; Brazil E-mail: <email>pedrotenorio28@gmail.com</email></corresp>
      </author-notes>
      <kwd-group xml:lang="en">
        <title>Keywords</title>
        <kwd>Cardiovascular Diseases/complications</kwd>
        <kwd>Uric Acid</kwd>
        <kwd>Human Serum Albumin</kwd>
        <kwd>Carotid Intima-Media Thickness</kwd>
        <kwd>Hypertension</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <p><bold>To the Editor</bold>,</p>
      <p>We carefully read the article entitled: "<italic>The relationship between the uric acid/albumin ratio and the carotid intima-media thickness in patients with hypertension</italic>", whose objective was to investigate the association of the uric acid/albumin ratio (UAR) and carotid intima-media thickness (CIMT) in hypertensive patients.<sup><xref ref-type="bibr" rid="B1">1</xref></sup> Although the present study demonstrated a significant correlation between UAR and CIMT, with UAR showing greater discriminatory capacity for increased CIMT values than uric acid and albumin alone and than the other inflammatory markers analyzed in the study, such as the systemic immune inflammation index (III), the neutrophil/lymphocyte ratio (NLR), the platelet/lymphocyte ratio (PLR) and the C-reactive protein/albumin ratio (CAR),<sup><xref ref-type="bibr" rid="B1">1</xref></sup> some aspects observed, when reading the article, are worthy of note.</p>
      <p>The classification of patients into groups of increased and normal CIMT used, as a cutoff point, a value of 0.9mm, in line with the normal value recommended in the guidelines of the European Society of Cardiology (ESC).<sup><xref ref-type="bibr" rid="B2">2</xref>,<xref ref-type="bibr" rid="B3">3</xref></sup> This simplification, however, can lead to classification errors in different populations and age groups, in which similar values may be within the normal range.<sup><xref ref-type="bibr" rid="B2">2</xref></sup> This was evidenced by Homma et al.,<sup><xref ref-type="bibr" rid="B4">4</xref></sup> through the finding that in aging, the increase in CIMT may be due to a process of diffuse intimal thickening and not necessarily the formation of atherosclerotic plaques. Given this, we consider it important to stratify the studied population by sex, age, and ethnicity, given the existence of variability among these individuals, which may influence an underestimation of the results.</p>
      <p>In the Vascular Ultrasonography positioning of the Department of Cardiovascular Imaging of the Brazilian Society of Cardiology &#8211; 2019,<sup><xref ref-type="bibr" rid="B5">5</xref></sup> it is recommended that after acquiring numerical CIMT data, the average values should be compared with already existing reference values in accordance with the normative tables of the ELSA-Brazil, CAPS or MESA studies. The decision on which table to use will depend on the individual&#8217;s gender, age, and ethnicity. It should be added in the conclusion whether the measurement is above or below the 75th percentile, in addition to the table used with its bibliographic reference. Therefore, the cutoff point used in the methodology may lead to confusion bias.</p>
      <p>However, the presence of atheromatous carotid plaque was not described in the groups since plaque identification is the main reclassifier of cardiovascular risk. Furthermore, the classification of the stage of hypertension in the selected group, according to the 2020 Arterial Hypertension Guideline,<sup><xref ref-type="bibr" rid="B6">6</xref></sup> confers a greater risk for target organ damage the higher the blood pressure levels, in addition to greater endothelial dysfunction and arterial vascular remodeling.</p>
      <p>As evidenced in the methodology, patients with congestive heart failure, secondary hypertension, moderate to severe valvular heart disease, coronary artery disease, chronic kidney or liver disease, malignancy, active infection, and chronic inflammatory disease, in addition to those taking medications that affect serum levels of uric acid and/or albumin and those with malnutrition.<sup><xref ref-type="bibr" rid="B1">1</xref></sup> However, we observed that individuals affected by peripheral arterial obstructive disease were not included in the research exclusion criteria, which may confuse the results presented since the evidence regarding the correlation between atherosclerotic deterioration of the arterial wall in peripheral vascular territories and the increase in CIMT, have already been demonstrated for some decades.<sup><xref ref-type="bibr" rid="B7">7</xref></sup> It is, therefore, necessary to consider this comorbidity among the exclusion criteria for a better analysis of the results obtained in the study.</p>
      <p>We also understand that it is necessary to stratify the diabetic patients included in the study in relation to the antidiabetic therapy used, given its potential to reduce CIMT. This effect was demonstrated, by way of illustration, in studies that analyzed drugs such as liraglutide<sup><xref ref-type="bibr" rid="B8">8</xref></sup> and metformin.<sup><xref ref-type="bibr" rid="B9">9</xref></sup> Due to these aspects, stratifying individuals in relation to the hypoglycemic agent used, the duration of treatment, and the dose used emerges as a relevant factor for a better interpretation of the association between UAR and CIMT.</p>
      <p>Finally, the correlation between diabetes mellitus and vascular calcification<sup><xref ref-type="bibr" rid="B10">10</xref>,<xref ref-type="bibr" rid="B11">11</xref></sup> is well established, which occurs, among other aspects, due to prolonged exposure of the smooth muscle fibers of the tunica media to hyperglycemia.<sup><xref ref-type="bibr" rid="B12">12</xref></sup> Due to this, it is inferred that the duration of illness presented by individuals affected by diabetes mellitus can be a predictor of this process, in addition to the fact that calcifying sclerosis of the media can be another confounder of the results presented, thus justifying the need for stratify diabetic patients according to the duration of illness.</p>
    </body>
    <response response-type="reply" xml:lang="en" id="R2">
      <front-stub>
        <article-categories>
          <subj-group subj-group-type="heading">
            <subject>Reply</subject>
          </subj-group>
        </article-categories>
        <title-group>
          <article-title>Reply</article-title>
        </title-group>
        <contrib-group>
          <contrib contrib-type="author">
            <name>
              <surname>&#350;ayl&#305;k</surname>
              <given-names>Faysal</given-names>
            </name>
          </contrib>
          <contrib contrib-type="author">
            <name>
              <surname>&#199;&#305;nar</surname>
              <given-names>Tufan</given-names>
            </name>
          </contrib>
          <contrib contrib-type="author">
            <name>
              <surname>Sel&#231;uk</surname>
              <given-names>Murat</given-names>
            </name>
          </contrib>
          <contrib contrib-type="author">
            <name>
              <surname>Tanbo&#287;a</surname>
              <given-names>&#304;brahim Halil</given-names>
            </name>
          </contrib>
        </contrib-group>
      </front-stub>
      <body>
        <p><bold>Dear Editor</bold>,</p>
        <p>We thank to authors for their valuable comments regarding our study entitled "The relationship between the uric acid/albumin ratio and the carotid intima-media thickness in patients with hypertension".<sup><xref ref-type="bibr" rid="B13">1</xref></sup></p>
        <p>We agree with the authors on the issue that age is correlated with carotid intima-media thickness (CIMT) irrespective of the formation of atherosclerotic plaques,<sup><xref ref-type="bibr" rid="B14">2</xref></sup> and the high CIMT group in our study was older than the low CIMT group. However, we eliminated this confounding factor by adding this variable in the multivariable model to get an adjusted odds ratio for uric acid/albumin ratio (UAR) for a high CIMT. Since there was no difference between the groups in terms of gender and such a parameter was also not associated with a high CIMT based on the univariable logistic regression analysis, we did not input that variable in the multivariable model. Finally, the population in our study consisted of only white Caucasian ethnicity, and there were no patients from other ethnic groups.</p>
        <p>The cutoff value for the discrimination of high and low CIMT groups was 0.9 mm, as suggested by the guidelines of the European Society of Cardiology.<sup><xref ref-type="bibr" rid="B15">3</xref></sup> Because this cutoff value was also used to determine the patients having high cardiovascular risk in the literature, we applied this cutoff value in our study.<sup><xref ref-type="bibr" rid="B16">4</xref></sup></p>
        <p>It is a well-known issue that the presence of atheromatous plaque is an independent predictor of cardiovascular risk.<sup><xref ref-type="bibr" rid="B17">5</xref></sup> The study aimed to evaluate the relationship between the UAR and CIMT. Thus, we did not investigate the presence of atheromatous plaque and its predictive role in cardiovascular risk.</p>
        <p>We agree with the authors on the relationship between the stage of hypertension and the risk of target organ damage, including vascular remodeling and endothelial dysfunction.<sup><xref ref-type="bibr" rid="B18">6</xref></sup> However, the vast majority of patients had already had hypertension diagnosed before enrollment in the study and were on anti-hypertensive treatment for a while. With the aid of anti-hypertensive drugs, blood pressure values were normalized in most patients. With this, the classification of hypertension based on recommended guidelines was not applicable in our study. Therefore, we could not evaluate the impact of the degree of hypertension on CIMT in this study. As mentioned by the authors, there is strong evidence regarding peripheral arterial deterioration and higher CIMT.<sup><xref ref-type="bibr" rid="B19">7</xref></sup> Thus, we excluded the patients with peripheral arterial disease from the study. However, we did not mention it in the exclusion criterion.</p>
        <p>The frequency of patients with and without diabetes mellitus (DM) was similar between high and low CIMT groups in our study (p-value = 0.280). Additionally, DM was not associated with high CIMT in the univariable logistic regression analysis. Thus, there was no impact of DM with having a high CIMT in our study. Additionally, diabetic patients with longer disease duration might develop micro- and macro-vascular complications. Due to the difficult calculation of CIMT in such patients, we did not include these patients in this study. We acknowledge that anti-diabetic drugs, including liraglutide and metformin, might have effects on CIMT.<sup><xref ref-type="bibr" rid="B20">8</xref>,<xref ref-type="bibr" rid="B21">9</xref></sup> On the other hand, GLT-1 inhibitors such as liraglutide have been recently used for the treatment of DM in our country. As we described above, because of the homogeneous distribution of diabetic patients between the study groups, we did not consider that DM had a biased impact on CIMT in this study. However, we did not collect data regarding the duration of DM as well as dosage and the duration of anti-diabetic drugs. Thus, these limitations might be added in the limitations part of the text.</p>
      </body>
    </response>
  </sub-article>
</article>
