Arq Bras Cardiol abc Arquivos Brasileiros de Cardiologia Arq. Bras. Cardiol. 0066-782X 1678-4170 Sociedade Brasileira de Cardiologia - SBC PNFRZxpxMfdksyQNL76LNSD S0066-782X2023000700901 00901 10.36660/abc.20230048 Carta ao Editor Qual a Eficácia do Índice Imune Inflamatório Sistêmico na Etiopatogenia da Ectasia Isolada da Artéria Coronária? 0000-0001-8634-1823 Toprak Kenan 1 0000-0002-4297-1820 Kaplangoray Mustafa 2 0000-0003-1784-3584 Inanır Mehmet 3 Memioğlu Tolga 3 Harran University Department of Cardiology Sanliurfa Turquia Harran University - Department of Cardiology, Sanliurfa – Turquia Bilecik Şeyh Edebali Üniversitesi – Cardiology Bilecik Turquia Bilecik Şeyh Edebali Üniversitesi – Cardiology, Bilecik – Turquia Abant Izzet Baysal University Cardiology Department Bolu Turquia Abant Izzet Baysal University - Cardiology Department, Bolu – Turquia Correspondência: Kenan Toprak • Harran University Faculty of Medicine - Department of Cardiology - viranşehir yolu Sanliurfa 63300 – Turquia E-mail: kentoprak@hotmail.com 04 09 2023 2023 120 7 e20230048 19 01 2023 09 02 2023 09 02 2023 This is an open-access article distributed under the terms of the Creative Commons Attribution License Palavras-chave Doença Arterial Coronariana/complicações Dilatação Patológica Biomarcadores Inflamação Imune Sistêmica

A ectasia isolada da artéria coronária (EIAC) é frequentemente encontrada na prática clínica com métodos de imagem invasivos crescentes, e nosso conhecimento sobre sua etiologia, prognóstico e abordagens de tratamento está aumentando diariamente.1,2 Lemos com grande interesse o recente estudo retrospectivo de Dindas et al.,3 que trata da relação entre o Índice de Inflamação Imunológica Sistêmica (IIS) e EIAC.3 Foi sugerido que neutrófilos, plaquetas e linfócitos IIS coletados em uma única fração podem ser um bom indicador de inflamação e resposta imune.4 Vários estudos mostraram que o IIS pode ter um valor prognóstico mais potente do que os marcadores inflamatórios convencionais, como Relação Neutrófilos/Linfócitos (RNL) e Relação Plaquetas/Linfócitos (RPL).5 Gostaríamos de comentar sobre o artigo bem elaborado e apresentado,que pensamos contribuir significativamente para a literatura.

Primeiramente, na análise da curva Receiver Operating Characteristic (ROC) do artigo de Dindas et al.,3 concluiu-se que IIS previu pacientes com EIAC melhor do que RNL, RPL e Relação Monócitos/HDL (RMH).3 Na análise da curva ROC do artigo de Dindas et al.,3 observou-se que IIS tinha maior AUC do que RNL, RPL e RMH, e a partir desses resultados, concluiu-se que IIS previu pacientes isolados com EC melhor do que RNL, RPL e RMH. No entanto, nenhuma comparação estatisticamente pareada foi feita entre as curvas ROC. Portanto, é difícil olhar apenas para os valores numéricos dos valores AUC e dizer que IIS é um preditor EIAC mais forte e valioso do que RNL, RPL e RMH. Na verdade, uma vez que a AUC de SII está próxima da AUC de RNL (0,832 vs. 0,780), uma comparação estatística pareada entre SII e RNL é essencial.6,7

Em segundo lugar, pacientes com EIAC, DAC obstrutiva sem ectasia coronariana e pacientes com artérias coronárias angiograficamente normais foram comparados no estudo para formar três grupos. No entanto, sabe-se que a ectasia coronariana é considerada uma variante da doença arterial coronariana e muitas vezes é detectada concomitantemente à DAC obstrutiva, em vez de ser isolada.8,9 Na verdade, a classificação de Markis não é uma classificação usada apenas para coronariopatia isolada ectasia arterial.9 Nesse contexto, pensamos que a inclusão de pacientes com DAC obstrutiva acompanhada de ectasia coronariana no estudo pode revelar mais claramente o efeito do IIS no EIAC.

Referências Toprak K Kaplangoray M Palice A The Impact of C-Peptide and Diabetes Mellitus on Coronary Ectasia and Effect of Coronary Ectasia and C-Peptide on Long-Term Outcomes: A Retrospective Cohort Study Int J Clin Pract 2022 10 8 2022 7910566 7910566 10.1155/2022/7910566 1 Toprak K, Kaplangoray M, Palice A. The Impact of C-Peptide and Diabetes Mellitus on Coronary Ectasia and Effect of Coronary Ectasia and C-Peptide on Long-Term Outcomes: A Retrospective Cohort Study. Int J Clin Pract. 2022 Oct 8;2022:7910566. doi: 10.1155/2022/7910566. Toprak K Kaplangoray M Altiparmak İ.H Taşcanov M. B Güngören F Fedai H Can increased intestinal permeability and low-grade endotoxemia be the triggering pathogenesis in isolated coronary artery ectasia? Coronary Artery Disease 2022 12 13 10.1097/MCA.0000000000001209 2 Toprak K, Kaplangoray M, Altiparmak İ. H, Taşcanov M. B, Güngören F, Fedai H, et al. Can increased intestinal permeability and low-grade endotoxemia be the triggering pathogenesis in isolated coronary artery ectasia?. Coronary Artery Disease. 2022 Dec 13. DOI:10.1097/MCA.0000000000001209. Dindas F Koyun E Turkyilmaz E Abacioglu OO Yildirim A Sahin A Systemic Immune Inflammation Index is a Novel Marker in Predicting the Presence and Severity of Isolated Coronary Artery Ectasia Arq Bras Cardiol 2023 01 9 120 1 e20220056 e20220056 10.36660/abc.20220056 3 Dindas F, Koyun E, Turkyilmaz E, Abacioglu OO, Yildirim A, Sahin A, et al. Systemic Immune Inflammation Index is a Novel Marker in Predicting the Presence and Severity of Isolated Coronary Artery Ectasia. Arq Bras Cardiol. 2023 Jan 9;120(1):e20220056. doi: 10.36660/abc.20220056. Hu B Yang XR Xu Y Sun YF Guo W Systemic immune-inflammation index predicts prognosis of patients after curative resection for hepatocellular carcinoma Clin Cancer Res 2014 20 23 6212 6222 10.1158/10780432.CCR-14-0442 4 Hu B, Yang XR, Xu Y, Sun YF,Guo W.Systemic immune-inflammation index predicts prognosis of patients after curative resection for hepatocellular carcinoma. Clin Cancer Res. 2014;20(23):6212-22. DOI: 10.1158/10780432.CCR-14-0442 Gao Y Guo W Cai S Zhang F Shao F Zhang G Systemic immuneinflammation index (SII) is useful to predict survival outcomes in patients with surgically resected esophageal squamous cell carcinoma J Cancer 2019 10 14 3188 3196 10.7150/jca.30281 5 Gao Y, Guo W, Cai S,Zhang F, Shao F, Zhang G, et al. Systemic immuneinflammation index (SII) is useful to predict survival outcomes in patients with surgically resected esophageal squamous cell carcinoma. J Cancer. 2019;10(14):3188-96. DOI: 10.7150/jca.30281 Metz EC Herman BA Roe CA Statistical comparison of two ROC-curve estimates obtained from partially-paired datasets Med Decis Making 1998 01-03 18 1 110 121 10.1177/0272989X9801800118 6 Metz EC, Herman BA, Roe CA. Statistical comparison of two ROC-curve estimates obtained from partially-paired datasets. Med Decis Making. 1998 Jan-Mar;18(1):110-21. doi: 10.1177/0272989X9801800118. Vergara IA Norambuena T Ferrada E Slater AW Melo F StAR: a simple tool for the statistical comparison of ROC curves BMC Bioinformatics 2008 06 5 9 265 265 10.1186/1471-2105-9-265 7 Vergara IA, Norambuena T, Ferrada E, Slater AW, Melo F. StAR: a simple tool for the statistical comparison of ROC curves. BMC Bioinformatics. 2008 Jun 5;9:265. doi: 10.1186/1471-2105-9-265. Devabhaktuni S Mercedes A Diep J Ahsan C Coronary Artery Ectasia-A Review of Current Literature Curr Cardiol Rev 2016 12 4 318 323 10.2174/1573403×12666160504100159 8 Devabhaktuni S, Mercedes A, Diep J, Ahsan C. Coronary Artery Ectasia-A Review of Current Literature. Curr Cardiol Rev. 2016;12(4):318-323. doi: 10.2174/1573403×12666160504100159. Zhang Y Huang QJ Li XL Guo YL Zhu CG Wang XW Prognostic Value of Coronary Artery Stenoses, Markis Class, and Ectasia Ratio in Patients with Coronary Artery Ectasia Cardiology 2015 131 4 251 259 10.1159/000381702 9 Zhang Y, Huang QJ, Li XL, Guo YL, Zhu CG, Wang XW, et al. Prognostic Value of Coronary Artery Stenoses, Markis Class, and Ectasia Ratio in Patients with Coronary Artery Ectasia. Cardiology. 2015;131(4):251-9. doi: 10.1159/000381702. Carta ao Editor Carta-resposta Dindaş Ferhat Koyun Emin Türkyilmaz Erdem Abacioglu Ozge Ozcan Yıldırım Arafat Sahin Anil Dindar Barış Dogdus Mustafa Candan Ozkan

Para o editor,

Estamos satisfeitos que os autores tenham lido nosso artigo com grande interesse. De fato, como afirmado na introdução e no título de nosso estudo, objetivamos investigar a possível relação entre ectasia coronariana (EC) isolada e um novo parâmetro de inflamação, o Índice de Inflamação Imune Sistêmica (IIS), em pacientes com angina pectoris estável ou instável.1 Obtivemos resultados sugerindo que o IIS pode ser um índice mais eficaz do que outros parâmetros inflamatórios hematológicos na distinção de pacientes com EC isolada.1 Uma comparação estatística pareada não foi incluída em nosso estudo porque pode estar fora do objetivo principal do estudo. No entanto, existem exemplos de artigos na literatura atual que não foram comparados com comparações pareadas com valores de corte próximos na análise ROC de parâmetros numéricos.2,3 Além disso, muitos estudos separados na literatura mostram que o IIS tem um valor preditivo mais forte do que a Razão Neutrófilo/Linfócito (RNL) em pacientes com doenças cardiovasculares.4–6

O autor tem razão ao enfatizar que o isolamento da EC não deve constituir um conceito diferente de doença arterial coronariana. Enquanto a EC isolada foi definida como a ausência de evidência de estenose coronariana acompanhando a ectasia em estudos anteriores,7 a EC isolada foi definida em estudos recentes como a ausência de uma lesão que cause mais de 50% de obstrução acompanhando a ectasia.3,8 À luz dessa informação, nosso estudo tentou mostrar o efeito inflamatório óbvio da IIS examinando o grupo de pacientes com estenose da artéria coronária epicárdica menor que 50% acompanhada de ectasia no grupo EC isolado.1 No entanto, avaliar pacientes com EC de tipo misto com mais de 50% de obstrução será muito impressionante como para ser ignorado em estudos futuros.

Referências Dindas F Koyun E Turkyilmaz E Abacioglu OO Yildirim A Sahin A Systemic Immune Inflammation Index is a Novel Marker in Predicting the Presence and Severity of Isolated Coronary Artery Ectasia Arq Bras Cardiol 2023 01 9 120 1 e20220056 10.36660/abc.20220056 1 Dindas F, Koyun E, Turkyilmaz E, Abacioglu OO, Yildirim A, Sahin A, et al. Systemic Immune Inflammation Index is a Novel Marker in Predicting the Presence and Severity of Isolated Coronary Artery Ectasia. Arq Bras Cardiol. 2023 Jan 9;120(1):e20220056. doi: 10.36660/abc.20220056. Huang H Liu Q Zhu L Zhang Y Lu X Wu Y Liu L Prognostic Value of Preoperative Systemic Immune-Inflammation Index in Patients with Cervical Cancer Sci Rep. 2019 03 1 9 1 3284 3284 10.1038/s41598-019-39150-0 2 Huang H, Liu Q, Zhu L, Zhang Y, Lu X, Wu Y, Liu L. Prognostic Value of Preoperative Systemic Immune-Inflammation Index in Patients with Cervical Cancer. Sci Rep. 2019 Mar 1;9(1):3284. doi: 10.1038/s41598-019-39150-0. Dereli S Çerik İB Kaya A Bektaş O Assessment of the Relationship Between C-Reactive Protein-to-Albumin Ratio and the Presence and Severity of Isolated Coronary Artery Ectasia Angiology 2020 10 71 9 840 846 10.1177/0003319720930983 3 Dereli S, Çerik İB, Kaya A, Bektaş O. Assessment of the Relationship Between C-Reactive Protein-to-Albumin Ratio and the Presence and Severity of Isolated Coronary Artery Ectasia. Angiology. 2020 Oct;71(9):840-6. doi: 10.1177/0003319720930983. Candemir M Kiziltunç E Nurkoç S Şahinarslan A Relationship Between Systemic Immune-Inflammation Index (SII) and the Severity of Stable Coronary Artery Disease Angiology 2021 07 72 6 575 581 10.1177/0003319720987743 4 Candemir M, Kiziltunç E, Nurkoç S, Şahinarslan A. Relationship Between Systemic Immune-Inflammation Index (SII) and the Severity of Stable Coronary Artery Disease. Angiology. 2021 Jul;72(6):575-81. doi: 10.1177/0003319720987743. Erdoğan M Erdöl MA Öztürk S Durmaz T Systemic immune-inflammation index is a novel marker to predict functionally significant coronary artery stenosis Biomark Med 2020 11 14 16 1553 1561 10.2217/bmm-2020-0274 5 Erdoğan M, Erdöl MA, Öztürk S, Durmaz T. Systemic immune-inflammation index is a novel marker to predict functionally significant coronary artery stenosis. Biomark Med. 2020 Nov;14(16):1553-61. doi: 10.2217/bmm-2020-0274. Kelesoglu S Yilmaz Y Elcık D Kalay N Systemic immune inflammation index: a novel predictor for coronary collateral circulation Perfusion 2022 09 37 6 605 612 10.1177/02676591211014822 6 Kelesoglu S, Yilmaz Y, Elcık D, Kalay N. Systemic immune inflammation index: a novel predictor for coronary collateral circulation. Perfusion. 2022 Sep;37(6):605-12. doi: 10.1177/02676591211014822. Zhang Y Huang QJ Li XL Guo YL Zhu CG Wang XW Xu B Gao RL Li JJ Prognostic Value of Coronary Artery Stenoses, Markis Class, and Ectasia Ratio in Patients with Coronary Artery Ectasia Cardiology 2015 131 4 251 259 10.1159/000381702 7 Zhang Y, Huang QJ, Li XL, Guo YL, Zhu CG, Wang XW, Xu B, Gao RL, Li JJ. Prognostic Value of Coronary Artery Stenoses, Markis Class, and Ectasia Ratio in Patients with Coronary Artery Ectasia. Cardiology. 2015;131(4):251-9. doi: 10.1159/000381702. Özkan B Örsçelik Ö Yıldırım Yaroğlu H Balcı Ş Özcan MK Çelik A Özcan IT Association between serum adropin levels and isolated coronary artery ectasia in patients with stable angina pectoris Anatol J Cardiol 2019 11 22 5 250 255 10.14744/AnatolJCardiol.2019.90349 8 Özkan B, Örsçelik Ö, Yıldırım Yaroğlu H, Balcı Ş, Özcan MK, Çelik A, Özcan IT. Association between serum adropin levels and isolated coronary artery ectasia in patients with stable angina pectoris. Anatol J Cardiol. 2019 Nov;22(5):250-5. doi: 10.14744/AnatolJCardiol.2019.90349 Letter to the Editor How Effective is the Systemic Inflammatory Immune Index in the Etiopathogenesis of Isolated Coronary Artery Ectasia? 0000-0001-8634-1823 Toprak Kenan 1 0000-0002-4297-1820 Kaplangoray Mustafa 2 0000-0003-1784-3584 Inanır Mehmet 3 Memioğlu Tolga 3 Sanliurfa Turkey Harran University - Department of Cardiology, Sanliurfa – Turkey Bilecik Turkey Bilecik Şeyh Edebali Üniversitesi – Cardiology, Bilecik – Turkey Bolu Turkey Abant Izzet Baysal University - Cardiology Department, Bolu – Turkey Mailing Address: Kenan Toprak • Harran University Faculty of Medicine - Department of Cardiology - viranşehir yolu Sanliurfa 63300 – Turkey E-mail: kentoprak@hotmail.com Keywords Coronary Artery Disease/complications Dilatation Pathologic, Sistemic Inflammation Immune

Isolated coronary artery ectasia (ICAE) is frequently encountered in clinical practice with increasing invasive imaging methods, and our knowledge about its etiology, prognosis, and treatment approaches is increasing daily.1,2 We read with great interest the recent retrospective study of Dindas et al.,3 which deals with the relationship between the Systemic Immune Inflammation Index (SII) and ICAE.3 It has been suggested that SII neutrophils, platelets, and lymphocytes collected in a single fraction may be a good indicator of inflammation and immune response.4 Various studies have shown that SII may have a more potent prognostic value than conventional inflammatory markers such as Neutrophil Lymphocyte Ratio (NLR) and Platelet Lymphocyte Ratio (PLR).5 We would like to comment on the well-designed and presented article, which we think will contribute significantly to the literature.

Firstly, in the Receiver Operating Characteristic (ROC) curve analysis of Dindas et al.3 article, it was seen that SII had a higher area under the curve (AUC) than NLR, PLR, and MHR, and from these results, it was concluded that SII predicted ICAE patients better than NLR, PLR and Monocyte HDL Ratio (MHR).3 In the ROC curve analysis of Dindas et al.3 article, it was seen that SII had higher AUC than NLR, PLR, and MHR, and from these results, it was concluded that SII predicted isolated CE patients better than NLR, PLR, and MHR. However, no statistically pairwise comparison was made between ROC curves. Therefore, it is difficult to look at the numerical values of the AUC values alone and say that SII is a stronger and more valuable ICAE predictor than NLR, PLR, and MHR. As a matter of fact, since the AUC of SII is close to the AUC of NLR (0.832 vs. 0.780), a pairwise statistical comparison between SII and NLR is essential.6,7

Secondly, patients with ICAE, obstructive CAD without coronary ectasia, and patients with angiographically normal coronary arteries were compared in the study to form three groups. However, it is known that coronary ectasia is considered a variant of coronary artery disease and is often detected concomitantly with obstructive CAD rather than being isolated.8,9 As a matter of fact, the Markis classification is not a classification used only for isolated coronary artery ectasia.9 In this context, we think that including patients with obstructive CAD accompanied by coronary ectasia in the study may reveal the effect of SII on ICAE more clearly.

Letter to The Editor Reply Dindaş Ferhat Koyun Emin Türkyilmaz Erdem Abacioglu Ozge Ozcan Yıldırım Arafat Sahin Anil Dindar Barış Dogdus Mustafa Candan Ozkan

To the Editor,

We are pleased that the authors read our article with great interest. In fact, as stated in the introduction and title of our study, we aimed to investigate the possible relationship between isolated coronary ectasia (CE) and a new inflammation parameter, Systemic Immune Inflammation Index (SII), in patients with stable or unstable angina pectoris.1 We obtained results suggesting that SII may be a more effective index than other hematological inflammatory parameters in distinguishing patients with isolated CE.1 A pairwise statistical comparison was not included in our study because it may be outside the study's main purpose. However, there are examples of articles in the current literature that have not been compared with pairwise comparisons with close cut-off values in ROC analysis of numerical parameters.2,3 In addition, many separate studies in the literature show that SII has a stronger predictive value than Neutrophil to Lymphocyte Ratio (NLR) in patients with cardiovascular diseases.4–6

The author is right in emphasizing that the isolation of CE should not constitute a concept other than coronary artery disease. While isolated CE was defined as the absence of evidence of coronary stenosis accompanying ectasia in previous studies,7 isolated CE has been defined in recent studies as the absence of a lesion that causes more than 50% obstruction accompanying ectasia.3,8 In light of this information, our study tried to show the obvious inflammatory effect of SII by examining the patient group with epicardial coronary artery stenosis of less than 50% accompanied by ectasia in the isolated CE group.1 However, evaluating patients with mixed-type CE with more than 50% obstruction will be too impressive to ignore in future studies.