Vol.:(0123456789) 1 3 European Archives of Oto-Rhino-Laryngology https://doi.org/10.1007/s00405-019-05492-8 LETTER TO THE EDITOR It is time to take action to prevent cardiovascular disease in postirradiation head and neck cancer patients Yu Chun Yeh 1  · Kai Min Fang 2  · Wan‑Lun Hsu 3  · Li‑Jen Liao 2,4,5 Received: 25 May 2019 / Accepted: 29 May 2019 © Springer-Verlag GmbH Germany, part of Springer Nature 2019 Keywords Head and neck cancer · Irradiation · Cardiovascular disease · Statistical issues Dear Editor, Regarding our recent publication about the role of ultrasound measurement of carotid intima-media thickness in head and neck cancer survivors [1], we thank the readers for remind- ing us of the possibility of estimation bias and sparse data bias and suggesting some methods of avoiding these types of bias. As suggested, we performed bootstrapping analysis of our original data, and we showed the results of 1000-sam- ple bootstrapping for the β-coefcients of multivariate lin- ear regression in Table 1. The coefcient is 0.129 (95% CI 0.054–0.204) for irradiation related to mean carotid intima- media thickness (CIMT), with the theory of regression to the mean. After repeated bootstrapping analysis, we believe the results further support our hypothesis. Due to the limitations of a small sample size, we found large odds ratios (ORs). We further used Firth penalization to recheck the odds ratios for signifcant variables identi- fed in multivariate logistic regression analysis; the original published regression analysis results were compared to the new results after Firth penalization in Table 2. We found that the OR for developing cardiovascular disease (CVD) after irradiation in patients with an abnormal mean CIMT (≥ 1.0 mm, which indicates a risk of developing CVD) is slightly diferent from the original published value; the new OR is 7.53 (95% CI 1.36–41.81); however, the positive OR still supports our hypothesis that irradiation to the neck is an independent risk factor for CVD. As mentioned in our publication, some previous studies reported that irradiation for HNC wound-induced extracra- nial carotid stenosis was associated with an increased CVD risk [2–5]. Overall, our results and related published studies support that irradiation to the neck is positively related to CIMT and This comment refers to the article available at https://doi. org/10.1007/s00405-019-05302-1. * Li-Jen Liao liaolj@ntu.edu.tw; deniro@mail2000.com.tw Yu Chun Yeh rambleurban@gmail.com Kai Min Fang u701048@gmail.com Wan-Lun Hsu lun0112@ms26.hinet.net 1 Department of Family Medicine, Far Eastern Memorial Hospital, New Taipei, Taiwan 2 Department of Otolaryngology Head and Neck Surgery, Far Eastern Memorial Hospital, No. 21, Sec. 2, Nanya S. Rd., Banqiao Dist., New Taipei 220, Taiwan ROC 3 Genomics Research Center, Academia Sinica, Taipei, Taiwan 4 Department of Electrical Engineering, Yuan Ze University, Taoyüan, Taiwan 5 Biomedical Engineering Ofce, Far Eastern Memorial Hospital, New Taipei, Taiwan Table 1 Results of 1000-sample bootstrapping for the β-coefcients of multivariate linear regression β-coef. β coefcient, 95% CI 95% confdence interval, BMI body mass index, HTN hypertension, DM diabetes mellitus Risk factors β-Coef. (95% CI) P value Age 0.006 (0.004 to 0.008) 0.001 BW 0.003 (0.001 to 0.005) 0.011 HTN 0.107 (0.024 to 0.179) 0.017 DM − 0.079 (− 0.215 to 0.079) 0.237 Hyperlipidemia − 0.012 (− 0.145 to 0.131) 0.845 Smoking − 0.023 (− 0.127 to 0.107) 0.688 Irradiation 0.129 (0.054 to 0.204) 0.001