Association between the Severity of Coronary Artery Disease and Lung Cancer: A Pilot Cross-Sectional Study. / Associação entre a Gravidade da Doença Arterial Coronariana e Câncer de Pulmão: Um Estudo Piloto Transversal.

BACKGROUND: The direct relationship between coronary artery disease (CAD) and lung cancer is not well known. OBJECTIVE: To investigate the association between the anatomical severity of CAD and lung cancer. METHODS: Three-hundred study patients, including 75 recently diagnosed lung cancer patients and 225 matched non-cancer patients, underwent coronary angiography during hospitalization without previous percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). The SYNTAX score (SXscore) was used to assess the severity of CAD. A high SXscore (SXhigh) grade was defined as SXscore > 15 (the highest quartile of the SXscore). The Cochran-Armitage test for trend was used to assess the distribution of patients' SXscores. Logistic regression analysis was used to assess the association between the severity of CAD and lung cancer. P-values were set when significance level was 5%. RESULTS: The distribution trend of patients' SXscore by quartiles was different between lung cancer patients and control patients (from the lowest to the highest quartile: 20.0%, 20.0%, 24.0%, 36.0% vs. 26.7%, 26.2%, 25.8%, 21.3%, p=0.022). The SX high rate was higher in lung cancer patients than in control patients (36.0% vs. 21.3%, p=0.011).The highest quartile of the SXscore showed higher risk of lung cancer in comparison to the lowest quartile (OR: 2,250, 95%CI: 1,077 to 4,699 ; P-trend= 0.016). After adjustment, patients in the highest quartile of the SXscore had higher risk of lung cancer (OR: 2,149, 95%CI: 1,008 to 4,584; P-trend= 0.028). Patients with high SXscore (> 15) had 1,985 times more chances of having lung cancer (95%CI: 1,105-3,563, P= 0.022). CONCLUSIONS: The anatomical severity of CAD is associated with the risk of lung cancer, which indicates that a thorough lung cancer screening may be significant among severe CAD patients.

FUNDAMENTO: A relação direta entre a doença arterial coronariana (DAC) e o câncer de pulmão não é bem conhecida. OBJETIVO: Investigar a associação entre a gravidade anatômica da DAC e do câncer de pulmão. MÉTODOS: Trezentos pacientes, incluindo 75 recém-diagnosticados com câncer de pulmão e 225 pacientes correspondentes sem câncer, foram submetidos à angiografia coronária durante a internação, sem intervenção coronária percutânea (ICP) prévia nem enxerto de bypass da artéria coronária (CABG). O escore SYNTAX foi utilizado para avaliar a gravidade da DAC. Uma pontuação alta no escore foi definida como > 15 (o maior quartil do escore SYNTAX). O teste de tendência de Cochran-Armitage foi utilizado para verificar a distribuição dos escores dos pacientes. Uma análise de regressão logística foi utilizada para avaliar a associação entre a gravidade da DAC e o câncer de pulmão. Os valores de p foram estabelecidos quando o nível de significância era 5%. RESULTADOS: A tendência de distribuição dos escores SYNTAX dos pacientes por quartis foi diferente entre aqueles com câncer de pulmão e controles (do quartil mais baixo ao mais alto: 20,0%; 20,0%; 24,0%; 36,0% vs. 26,7%; 26,2%; 25,8%; 21,3%; p=0,022). A pontuação no escore SYNTAX foi mais alta em pacientes com câncer do que nos pacientes controle (36,0% vs. 21,3%, p=0,011).O maior quartil do escore demonstrou mais riscos de desenvolver câncer de pulmão em comparação ao quartil mais baixo (OR: 2.250, IC95%: 1.077 a 4.699 ; P -trend= 0,016). Após ajustes, os pacientes no maior quartil do escore SYNTAX tinham mais risco de desenvolver câncer de pulmão (OR: 2.1o49, IC95%: 1.008 a 4.584; P -trend= 0,028). Pacientes com escores SYNTAX alto (> 15) tinham 1.985 mais chances de ter câncer de pulmão (IC95%: 1.105­3.563, P= 0,022). CONCLUSÃO: A gravidade anatômica da DAC está associada ao risco de câncer de pulmão, o que indica que um rastreamento completo deste tipo de câncer possa ser mais significativo entre pacientes com DAC.

Associação entre a Gravidade da Doença Arterial Coronariana e Câncer de Pulmão: Um Estudo Piloto Transversal / Association between the Severity of Coronary Artery Disease and Lung Cancer: A Pilot Cross-Sectional Study

Resumo Fundamento A relação direta entre a doença arterial coronariana (DAC) e o câncer de pulmão não é bem conhecida. Objetivo Investigar a associação entre a gravidade anatômica da DAC e do câncer de pulmão. Métodos Trezentos pacientes, incluindo 75 recém-diagnosticados com câncer de pulmão e 225 pacientes correspondentes sem câncer, foram submetidos à angiografia coronária durante a internação, sem intervenção coronária percutânea (ICP) prévia nem enxerto de bypass da artéria coronária (CABG). O escore SYNTAX foi utilizado para avaliar a gravidade da DAC. Uma pontuação alta no escore foi definida como > 15 (o maior quartil do escore SYNTAX). O teste de tendência de Cochran-Armitage foi utilizado para verificar a distribuição dos escores dos pacientes. Uma análise de regressão logística foi utilizada para avaliar a associação entre a gravidade da DAC e o câncer de pulmão. Os valores de p foram estabelecidos quando o nível de significância era 5%. Resultados A tendência de distribuição dos escores SYNTAX dos pacientes por quartis foi diferente entre aqueles com câncer de pulmão e controles (do quartil mais baixo ao mais alto: 20,0%; 20,0%; 24,0%; 36,0% vs. 26,7%; 26,2%; 25,8%; 21,3%; p=0,022). A pontuação no escore SYNTAX foi mais alta em pacientes com câncer do que nos pacientes controle (36,0% vs. 21,3%, p=0,011).O maior quartil do escore demonstrou mais riscos de desenvolver câncer de pulmão em comparação ao quartil mais baixo (OR: 2.250, IC95%: 1.077 a 4.699 ; P -trend= 0,016). Após ajustes, os pacientes no maior quartil do escore SYNTAX tinham mais risco de desenvolver câncer de pulmão (OR: 2.1o49, IC95%: 1.008 a 4.584; P -trend= 0,028). Pacientes com escores SYNTAX alto (> 15) tinham 1.985 mais chances de ter câncer de pulmão (IC95%: 1.105-3.563, P= 0,022). Conclusão A gravidade anatômica da DAC está associada ao risco de câncer de pulmão, o que indica que um rastreamento completo deste tipo de câncer possa ser mais significativo entre pacientes com DAC.

Abstract Background The direct relationship between coronary artery disease (CAD) and lung cancer is not well known. Objective To investigate the association between the anatomical severity of CAD and lung cancer. Methods Three-hundred study patients, including 75 recently diagnosed lung cancer patients and 225 matched non-cancer patients, underwent coronary angiography during hospitalization without previous percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). The SYNTAX score (SXscore) was used to assess the severity of CAD. A high SXscore (SXhigh) grade was defined as SXscore > 15 (the highest quartile of the SXscore). The Cochran-Armitage test for trend was used to assess the distribution of patients' SXscores. Logistic regression analysis was used to assess the association between the severity of CAD and lung cancer. P-values were set when significance level was 5%. Results The distribution trend of patients' SXscore by quartiles was different between lung cancer patients and control patients (from the lowest to the highest quartile: 20.0%, 20.0%, 24.0%, 36.0% vs. 26.7%, 26.2%, 25.8%, 21.3%, p=0.022). The SX high rate was higher in lung cancer patients than in control patients (36.0% vs. 21.3%, p=0.011).The highest quartile of the SXscore showed higher risk of lung cancer in comparison to the lowest quartile (OR: 2,250, 95%CI: 1,077 to 4,699 ; P-trend= 0.016). After adjustment, patients in the highest quartile of the SXscore had higher risk of lung cancer (OR: 2,149, 95%CI: 1,008 to 4,584; P-trend= 0.028). Patients with high SXscore (> 15) had 1,985 times more chances of having lung cancer (95%CI: 1,105-3,563, P= 0.022). Conclusions The anatomical severity of CAD is associated with the risk of lung cancer, which indicates that a thorough lung cancer screening may be significant among severe CAD patients.

Doença Arterial Coronariana Anatômica Associada à Quimioterapia em Pacientes com Câncer de Pulmão Avaliada pelo Escore Angiográfico SYNTAX / Chemotherapy-Related Anatomical Coronary-Artery Disease in Lung Cancer Patients Evaluated by Coronary-Angiography SYNTAX Score

Resumo Fundamento A doença arterial coronariana (DAC) associada à quimioterapia está se tornando um tema emergente na prática clínica. Contudo, o mecanismo subjacente da quimioterapia associada à DAC permanence incerto. Objetivos O estudo investigou a associação entre a quimioterapia e as anomalias anatômicas ateroscleróticas das artérias coronárias dentre pacientes com cancer de pulmão. Métodos Foram incluídos pacientes submetidos à angiografia coronária (AGC), entre 2010 e 2017, com câncer de pulmão prévio. Os fatores de risco associados à DAC e os dados sobre o câncer de pulmão foram avaliados. Avaliamos as anomalias das artérias coronárias de acordo com o escore SYNTAX (SXescore) calculado à AGC. Na análise de regressão logística, o escore SYNTAX foi classificado como alto (SXescoreALTO) se ≥22. Os dados foram analisados através de estatística descritiva e análise de regressão. Resultados Ao todo, 94 pacientes foram incluídos no estudo. O SXescore foi mais alto no grupo com quimioterapia quando comparado com o grupo sem quimioterapia (25,25, IIQ [4,50-30,00] versus 16,50, IIQ [5,00-22,00]; p = 0,0195). A taxa do SXescoreALTO foi maior no grupo com quimioterapia do que no no grupo sem quimioterapia (58,33% versus 25,86; p = 0,0016). Tanto a análise de regressão logística univariada (OR: 4,013; 95% IC:1,655-9,731) quanto a multivariada (OR: 5,868; 95% IC:1,778-19,367) revelaram que a quimioterapia aumentou o risco de uma maior taxa do SXescoreALTO. A análise multivariada de regressão logística Stepwise mostrou que o risco para DAC anatômica mais grave aumenta com a quimioterapia como um todo em 5.323 vezes (95% IC: 2,002-14,152), e com o regime à base de platina em 5,850 vezes (95% IC: 2,027-16,879). Conclusões A quimioterapia está associada com a complexidade e gravidade anatômica da DAC, o que pode explicar, em parte, o maior risco de DAC associada à quimioterapia dentre pacientes com câncer de pulmão. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0)

Abstract Background Chemotherapy-related coronary artery disease (CAD) is becoming an emerging issue in clinic. However, the underlying mechanism of chemotherapy-related CAD remains unclear. Objective The study investigated the association between chemotherapy and atherosclerotic anatomical abnormalities of coronary arteries among lung cancer patients. Methods Patients undergoing coronary angiography (CAG) between 2010 and 2017, who previously had lung cancer, were examined. Risk factors associated with CAD and information about lung cancer were evaluated. We assessed coronary-artery abnormalities by SYNTAX score (SXscore) based on CAG. In logistic-regression analysis, we defined high SXscore (SXhigh) grade as positive if ≥22. Data were analyzed through descriptive statistics and regression analysis. Results A total of 94 patients were included in the study. The SXscore was higher in the chemotherapy group than in the non-chemotherapy group (25.25, IQR [4.50-30.00] vs. 16.50, IQR [ 5.00-22.00], p = 0.0195). The SXhigh rate was greater in the chemotherapy group than in the non-chemotherapy group (58.33% vs. 25.86; p = 0.0016). Both univariate (OR:4.013; 95% CI:1.655-9.731) and multivariate (OR:5.868; 95% CI:1.778-19.367) logistic-regression analysis revealed that chemotherapy increased the risk of greater SXhigh rates. Multivariate stepwise logistic-regression analysis showed the risk of more severe anatomical CAD is increased by chemotherapy as a whole by 5.323 times (95% CI: 2.002-14.152), and by platinum-based regimens by 5.850 times (95% CI: 2.027-16.879). Conclusions Chemotherapy is associated with anatomical complexity and severity of CAD, which might partly account for the higher risk of chemotherapy-related CAD among lung cancer patients. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0)

Chemotherapy-Related Anatomical Coronary-Artery Disease in Lung Cancer Patients Evaluated by Coronary-Angiography SYNTAX Score. / Doença Arterial Coronariana Anatômica Associada à Quimioterapia em Pacientes com Câncer de Pulmão Avaliada pelo Escore Angiográfico SYNTAX.

Background Chemotherapy-related coronary artery disease (CAD) is becoming an emerging issue in clinic. However, the underlying mechanism of chemotherapy-related CAD remains unclear. Objective The study investigated the association between chemotherapy and atherosclerotic anatomical abnormalities of coronary arteries among lung cancer patients. Methods Patients undergoing coronary angiography (CAG) between 2010 and 2017, who previously had lung cancer, were examined. Risk factors associated with CAD and information about lung cancer were evaluated. We assessed coronary-artery abnormalities by SYNTAX score (SXscore) based on CAG. In logistic-regression analysis, we defined high SXscore (SXhigh) grade as positive if ≥22. Data were analyzed through descriptive statistics and regression analysis. Results A total of 94 patients were included in the study. The SXscore was higher in the chemotherapy group than in the non-chemotherapy group (25.25, IQR [4.50-30.00] vs. 16.50, IQR [ 5.00-22.00], p = 0.0195). The SXhigh rate was greater in the chemotherapy group than in the non-chemotherapy group (58.33% vs. 25.86; p = 0.0016). Both univariate (OR:4.013; 95% CI:1.655-9.731) and multivariate (OR:5.868; 95% CI:1.778-19.367) logistic-regression analysis revealed that chemotherapy increased the risk of greater SXhigh rates. Multivariate stepwise logistic-regression analysis showed the risk of more severe anatomical CAD is increased by chemotherapy as a whole by 5.323 times (95% CI: 2.002-14.152), and by platinum-based regimens by 5.850 times (95% CI: 2.027-16.879). Conclusions Chemotherapy is associated with anatomical complexity and severity of CAD, which might partly account for the higher risk of chemotherapy-related CAD among lung cancer patients. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0).

Melatonin-Induced Protective Effects on Cardiomyocytes Against Reperfusion Injury Partly Through Modulation of IP3R and SERCA2a Via Activation of ERK1.

BACKGROUND: Melatonin is a neuroendocrine hormone synthesized primarily by the pineal gland that is indicated to effectively prevent myocardial reperfusion injury. It is unclear whether melatonin protects cardiac function from reperfusion injury by modulating intracellular calcium homeostasis. OBJECTIVE: Demonstrate that melatonin protect against myocardial reperfusion injury through modulating IP3R and SERCA2a to maintain calcium homeostasis via activation of ERK1 in cardiomyocytes. METHODS: In vitro experiments were performed using H9C2 cells undergoing simulative hypoxia/reoxygenation (H/R) induction. Expression level of ERK1, IP3R and SERCA2a were assessed by Western Blots. Cardiomyocytes apoptosis was detected by TUNEL. Phalloidin-staining was used to assess alteration of actin filament organization of cardiomyocytes. Fura-2 /AM was used to measure intracellular Ca2+ concentration. Performing in vivo experiments, myocardial expression of IP3R and SERCA2a were detected by immunofluorescence staining using myocardial ischemia/ reperfusion (I/R) model in rats. RESULTS: In vitro results showed that melatonin induces ERK1 activation in cardiomyocytes against H/R which was inhibited by PD98059 (ERK1 inhibitor). The results showed melatonin inhibit apoptosis of cardiomyocytes and improve actin filament organization in cardiomyocytes against H/R, because both could be reversed by PD98059. Melatonin was showed to reduce calcium overload, further to inhibit IP3R expression and promote SERCA2a expression via ERK1 pathway in cardiomyocytes against H/R. Melatonin induced lower IP3R and higher SERCA2a expression in myocardium that were reversed by PD98059. CONCLUSION: melatonin-induced cardioprotection against reperfusion injury is at least partly through modulation of IP3R and SERCA2a to maintain intracellular calcium homeostasis via activation of ERK1.

Melatonin-Induced Protective Effects on Cardiomyocytes Against Reperfusion Injury Partly Through Modulation of IP3R and SERCA2a Via Activation of ERK1 / Efeitos Protetores Induzidos pela Melatonina nos Cardiomiócitos Contra Lesões de Reperfusão Parcialmente Através da Modulação Dde IP3R e SERCA por Meio da Ativação de ERK1

Resumo Background: Melatonin is a neuroendocrine hormone synthesized primarily by the pineal gland that is indicated to effectively prevent myocardial reperfusion injury. It is unclear whether melatonin protects cardiac function from reperfusion injury by modulating intracellular calcium homeostasis. Objective: Demonstrate that melatonin protect against myocardial reperfusion injury through modulating IP3R and SERCA2a to maintain calcium homeostasis via activation of ERK1 in cardiomyocytes. Methods: In vitro experiments were performed using H9C2 cells undergoing simulative hypoxia/reoxygenation (H/R) induction. Expression level of ERK1, IP3R and SERCA2a were assessed by Western Blots. Cardiomyocytes apoptosis was detected by TUNEL. Phalloidin-staining was used to assess alteration of actin filament organization of cardiomyocytes. Fura-2 /AM was used to measure intracellular Ca2+ concentration. Performing in vivo experiments, myocardial expression of IP3R and SERCA2a were detected by immunofluorescence staining using myocardial ischemia/ reperfusion (I/R) model in rats. Results: In vitro results showed that melatonin induces ERK1 activation in cardiomyocytes against H/R which was inhibited by PD98059 (ERK1 inhibitor). The results showed melatonin inhibit apoptosis of cardiomyocytes and improve actin filament organization in cardiomyocytes against H/R, because both could be reversed by PD98059. Melatonin was showed to reduce calcium overload, further to inhibit IP3R expression and promote SERCA2a expression via ERK1 pathway in cardiomyocytes against H/R. Melatonin induced lower IP3R and higher SERCA2a expression in myocardium that were reversed by PD98059. Conclusion: melatonin-induced cardioprotection against reperfusion injury is at least partly through modulation of IP3R and SERCA2a to maintain intracellular calcium homeostasis via activation of ERK1.

Resumo Fundamento: A melatonina é um hormônio neuroendócrino sintetizado principalmente pela glândula pineal que é indicado para prevenir efetivamente a lesão de reperfusão miocárdica. Não está claro se a melatonina protege a função cardíaca da lesão de reperfusão através da modulação da homeostase do cálcio intracelular. Objetivo: Demonstrar que a melatonina protege contra a lesão de reperfusão miocárdica através da modulação de IP3R e SERCA para manter a homeostase de cálcio por meio da ativação de ERK1 em cardiomiócitos. Métodos: Foram realizados experimentos in vitro usando células H9C2 submetidas a indução de hipoxia / reoxigenação simulada (H/R). O nível de expressão de ERK1, IP3R e SERCA foi avaliado por Western Blots. A apoptose de cardiomiócitos foi detectada por TUNEL. A coloração de faloidina foi utilizada para avaliar a alteração da organização de filamentos de actina dos cardiomiócitos. Fura-2 / AM foi utilizado para medir a concentração intracelular de Ca2+. Realizando experiências in vivo, a expressão miocárdica de IP3R e SERCA foi detectada por coloração com imunofluorescência usando modelo de isquemia miocárdica / reperfusão (I/R) em ratos. Resultados: resultados in vitro mostraram que a melatonina induz a ativação de ERK1 em cardiomiócitos contra H/R que foi inibida por PD98059 (inibidor de ERK1). Os resultados mostraram que a melatonina inibe a apoptose dos cardiomiócitos e melhora a organização do filamento de actina em cardiomiócitos contra H/R, pois ambas poderiam ser revertidas pela PD98059. A melatonina mostrou reduzir a sobrecarga de cálcio, além de inibir a expressão de IP3R e promover a expressão de SERCA através da via ERK1 em cardiomiócitos contra H/R. A melatonina induziu menor IP3R e maior expressão de SERCA no miocárdio que foram revertidas pela PD98059. Conclusão: a cardioproteção induzida pela melatonina contra lesão de reperfusão é pelo menos parcialmente através da modulação de IP3R e SERCA para manter a homeostase de cálcio intracelular via ativação de ERK1.