To the Editor,I read the article entitled “High levels of HB-EGF and interleukin-18 are associated with a high risk of in-stent restenosis” by Jiang et al. (1) with great interest, recently published in Anatolian Journal of Cardiology 2015; 15: 907-12. The investigators reported that higher levels of heparin-binding epidermal growth factor-like growth factor (HB-EGF) and interleukin-18 (IL-18) are associated with a high risk of in-stent restenosis after percutaneous coronary intervention. Jiang et al. (1) demonstrated the significance of inflammation and higher HB-EGF and IL-8 levels for in-stent restenosis. However, because of some confounding factors, I would like to emphasize some important points to clarify the findings of this article.First, lesion-related characteristics, including ACC/AHA classification, total occlusion, ostial lesion, and severity of calcification, have strong relationship with in-stent restenosis (2). In the present study of Jiang et al. (1), there are no data about these significant predictors of in-stent restenosis for both groups. Higher incidence of complex lesions and lesions with high risk for in-stent restenosis in higher HB-EGF and IL-8 levels may be a reason of higher in-stent restenosis for this group. Hence, the investigators should consider these factors to clarify the exact significance of HB-EGF and IL-8 levels for in-stent restenosis.Second, the investigators did not report the treatment with some important medications that are known to prevent in-stent restenosis. Statins and renin–angiotensin–aldosterone system blockers reduce in-stent restenosis (3,4). Therefore, lower incidence of treatment with these drugs may be another reason for higher in-stent restenosis in patients with higher HB-EGF and IL-8 levels.Finally, it has been demonstrated that regular exercise training significantly reduces in-stent restenosis after percutaneous coronary intervention in patients with acute myocardial infarction (5). The investigators should comment on presence or absence of exercise training for each group.In conclusion, inflammation plays a significant role in the pathogenesis of atherosclerosis. However, to define higher HB-EGF and IL-8 levels as indicators of in-stent restenosis, lesion-related characteristics, medications, and regular exercise training should be taken into consideration.