ABC | Volume 114, Nº6, June 2020

Original Article Yang et al Chemotherapy-related coronary-artery disease Arq Bras Cardiol. 2020; 114(6):1004-1012 Statistical analysis Baseline descriptive statistics are presented as frequencies and percentages for categorical variables and mean ± standard deviation (SD) and median (interquartile range [IQR]) for continuous variables. The normality of data was assessed using the Skewness and Kurtosis normality test. Differences between the study groups were assessed by chi-square test or Fisher’s exact test for categorical data, and by student’s t test for continuous data. We used student’s t test to compare the groups’ means when variables were normally distributed, and a non-parametric test when they were not normally distributed. Chi-square or Fisher’s exact test were used to examine differences for categorical measures. We assessed the relationships between chemotherapy and CAD complexity by logistic-regression analysis, adjusting related covariates that included age, gender, BMI, smoking, family history of CVDs, hypertension, diabetes and hyperlipidemia. Odds ratios (ORs) and 95% confidence intervals [CIs] were calculated. P values were 2-tailed, and we set the level of significance at 0.05. All statistical analyses were performed using SAS software, version 9.3 (SAS Institute, Inc., Cary, North Carolina, USA). Results Patient characteristics A total of 94 patients who had previously had lung cancer and who underwent CAG at Chinese PLA General Hospital, between 2010 and 2017, were included in the study. Out of these, 73 were males and 21 females (M:F = 3.48). Eighty- five patients were diagnosed with non-small cell lung cancer, and the other 9 patients with small cell lung cancer. Thirty-six patients had histories of chemotherapy. Among the patients with chemotherapy, 28 patients received platinum-based regimens. Platinum-based regimens combining gemcitabine or docetaxel, and other agents, were used in non-small cell lung cancer patients, and double-platinum chemotherapy combined with etoposide was used in small cell lung cancer patients. One patient received anthracycline (pharmorubicin), which is known to have cardiac toxicity. Five patients received tyrosine kinase inhibitors (gefitinib). Three patients lacked detailed information about chemotherapy regimens. Fifty-eight patients did not receive any chemotherapy. There were no significant differences regarding conventional CAD risk factors (hypertension, hyperlipidemia, diabetes or smoking history) between the chemotherapy and non- chemotherapy groups. In the chemotherapy group, more patients took radiotherapy than in the non-chemotherapy group (p < 0.0001). The time interval range from cancer diagnosis to CAG was discrepant between the two groups. Patient characteristics are listed in Table 1. Analysis of association between chemotherapy and high SXscore Patients who underwent chemotherapy developed more- severe anatomical CAD than those who did not undergo chemotherapy. The SXscore was significantly 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). According to the SXscore grade definition, the percentage of SXhigh was significantly higher in the chemotherapy group than in the non-chemotherapy group (58.33% vs. 25.86%; p = 0.0016). Details are shown in Table 2. Radiotherapy is another important treatment for lung cancer. In our study, the SXscore was higher in the radiotherapy group than in the non-radiotherapy group (22.00, IQR[ 5.00–30.00] vs. 19.00, IQR[5.00–25.00]; p = 0.3045). The percentage of SXhigh was higher in the radiotherapy group than in the non-radiotherapy group (52.38% vs. 34.25%; p = 0.1319). However, there was no significant difference for either SXscore or SXhigh rates between the radiotherapy and non-radiotherapy groups. Compared with radiotherapy, chemotherapy showed worse effects on anatomical abnormalities of coronary arteries among lung cancer patients. Results are presented in Table 2. Univariate logistic-regression analysis showed that chemotherapy significantly increased the SXhigh rate by 4.013 times (95% CI:1.655–9.731). The OR of radiotherapy for SXhigh was 2.112 (95% CI: 0.790–5.646), which showed no obvious statistical significance. Smoking as a conventional cardiovascular risk factor was shown to significantly increase the SXhigh rate by 3.182 times (95% CI:1.327–7.628). The ORs of other cardiovascular risk factors for SXhigh were >1, but showed no obvious statistical significance. In multivariate logistic-regression analysis, chemotherapy was shown to increase the risk of CAD with more-severe anatomical abnormalities by 5.868 times (95% CI: 1.778-19.367). The ORs of radiotherapy and smoking for SXhigh were 1.124 (95% CI: 0.286–4.416) and 3.035 (95% CI: 1.036–8.893), respectively. Results are shown in Table 3. In multivariate stepwise logistic regression adjusted for related CAD risk factors (age, gender, BMI, smoking, family history of CVDs, hypertension, diabetes and hyperlipidemia) and lung cancer–related risk factors (history of radiotherapy and chemotherapy), chemotherapy as a whole and smoking were shown to significantly increase the SXhigh rate by 5.323 times (95% CI: 2.002–14.152) and by 3.646 times (95% CI: 1.374–9.678), respectively. Moreover, we detected that the effects of platinum-based regimen on anatomical CAD were similar: the OR of platinum-based regimen was 5.850 (95% CI: 2.027–16.879), and the OR of smoking was 3.670 (95% CI: 1.303–10339). Results are shown in Table 4. Discussion To the best of our knowledge, this study is the first to quantitatively demonstrate that chemotherapy is related to anatomical complexity and severity of CAD among lung cancer patients, using SXscore based on coronary angiograms. Antineoplastic therapy is frequently hindered by the development of cardiovascular complications such as heart failure, myocardial infarction, hypertension, thromboembolism, QT prolongation and bradycardia. 23 Until now, the most often reported chemotherapy-induced heart conditions have been cardiac dysfunction and heart failure, as evaluated by echocardiography. 1,24,25 Chemotherapy- related coronary-artery events are becoming important clinical problems among the cancer population who received 1006