Wang et al. BMC Cardiovasc Disord (2020) 20:510 https://doi.org/10.1186/s12872-020-01798-2

RESEARCH ARTICLE Open Access The characteristics and risk factors of in‑ restenosis in patients with percutaneous coronary intervention: what can we do Pengfei Wang1* , Haixia Qiao2, RuiJuan Wang1, Ruitian Hou1 and Jingtao Guo2

Abstract Background: Percutaneous coronary intervention (PCI) is a common treatment for patients with coronary heart disease, and intra-stent restenosis (ISR) is a serious complication after PCI. It’s necessary to identify the potential risk factors to provide evidence for the prevention of ISR. Methods: The patients who underwent coronary 1 year after PCI in our hospital from January 2017 to May 2019 were selected. The characteristics and results of clinical examination of ISR and no-ISR patients were com- pared, Multivariate logistic regression analyses were performed to identify the risk factors. Results: A total of 209 patients were included, the incidence of ISR after PCI was 30.62%. There were signifcant difer- ences on the hypertension, diabetes, number of coronary lesions, reasons for stent implantation, the diameter of stent, the length of stent and stent position between ISR group and no-ISR patients (all p < 0.05). The LDL-C in ISR groups was signifcantly higher than that of no-ISR group (p 0.048), there were no signifcant diferences between two groups in FPG, TG, TC, HDL-C, Apo A1, Apo B, LP-a and glycated= haemoglobin (all p > 0.05). The hypertension (OR 4.30, 95% CI 1.12–9.34), diabetes (OR 5.29, 95% CI 1.25–9.01), number of coronary artery lesions 2 (OR 4.84, 95% CI 1.21–9.55), LDL-C 1.9 mmol/L (OR 5.93, 95% CI 2.29–10.01), unstable (OR 2.92, 95% CI 1.20–4.55),≥ left anterior descending artery≥ (OR 4.01, 95% CI 1.73–7.58), diameter of stent 3 mm (OR 5.42, 95% CI 1.24–10.84), the length of stent > 20 mm (OR 3.06, 95% CI 1.19–5.22) were the independent≥ risk factor for ISR (all p < 0.05). Conclusion: It is necessary to take preventive measures against these risk factors to reduce ISR, and studies with larger sample size and longer follow-up on this issue are needed in the future. Keywords: In-stent restenosis, PCI, Cardiovascular, Risk, Prevention, Nursing

Summary graph of the results Te hypertension, diabetes, number of coronary artery lesions ≥ 2, LDL-C ≥ 1.9 mmol/L, unstable Te incidence of ISR was 30.62%. angina, left anterior descending artery, diameter of Te LDL-C in ISR groups was signifcantly higher stent ≥ 3 mm, the length of stent > 20 mm were inde- than that of no-ISR group. pendent risk factor for ISR.

Background *Correspondence: [email protected] With the continuous improvement of life quality, the 1 Department of Cardiology, Afliated Hospital of Chengde Medical College, No. 36 Nanyingzi Street, Chengde 067000, Hebei Province, global cardiovascular disease prevalence is in a continu- People’s Republic of China ous rising stage, and the mortality of cardiovascular dis- Full list of author information is available at the end of the article ease ranks frst, which is higher than that of tumors and

© The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativeco​ mmons​ .org/licen​ ses/by/4.0/​ . The Creative Commons Public Domain Dedication waiver (http://creativeco​ ​ mmons.org/publi​ cdoma​ in/zero/1.0/​ ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Wang et al. BMC Cardiovasc Disord (2020) 20:510 Page 2 of 6

other diseases [1, 2]. Te proportion of died patients with exercise, maintaining emotional stability, and rational use coronary heart disease (CHD) among the total number of of drugs. All received oral aspirin (AstraZeneca Pharma- deaths has increased from 8.6% in 1990 to 15.2% in 2013 ceutical Co., Ltd., H32026199, 0.1 g), the initial dose was [3]. With the intensifcation of the aging process, the 300 mg, and then 100 mg/time, once a day; at the same morbidity and mortality of CHD in various countries will time, ticagrelor tablets (AstraZeneca Pharmaceutical Co., continue to increase, which seriously threatens the health Ltd., J20171077, 90 mg), the initial dose was 180 mg, and of the people and brings a heavy social and economic then 90 mg once for every 12 h. burden [4]. Terefore, the prevention and treatment of coronary heart disease is extremely important. ISR diagnosis Percutaneous coronary intervention (PCI) is one of the All patients underwent coronary angiography 1 year after main treatments for patients with CHD, and intra-stent surgery. Left anterior, right anterior and head-foot axis restenosis (ISR) after PCI has gradually attracted clini- projections were used to observe coronary artery lesions, cal attention [5]. ISR refers to the plaque within 5 mm of and the degree of of the left main trunk, left ante- the edge of the stent after PCI and has a stenosis greater rior descending branch, right coronary artery and left cir- than 50% [6]. Te incidence of ISR for is 15–30% cumfex branch lesions were accurately evaluated. For the [7]. With the development of interventional technology, coronary artery angiography records, two interventional the comprehensive application of drug-eluting stents physicians were arranged to complete the corresponding and anti-proliferative drugs such as rapamycin, everoli- diagnosis independently. If there were any disagreement mus, etc. has improved the success rate of interventional in the diagnosis, a third doctor was referred. ISR was therapy [8], but the ISR problem has not been completely defned as the narrowing of the lumen diameter of the resolved. Terefore, it is very urgent to identify the ISR target vessel ≥ 50%, including the coronary in the related risk factors to provide evidence for the preven- stent and the ≤ 5 mm area of the stent [9]. tion of ISR. We attempted to evaluate the characteristics and risk factors of ISR in patients with PCI, to provide Data collection insights into the prophylaxis and treatment of ISR. We developed a uniformed form to collect following information for every included patients: (1) Te charac- Methods teristics of patients, including gender, age, drinking his- Ethical consideration tory, smoking history, antiplatelet drug use status (such Tis study was reviewed and approved by the Medical as aspirin, clopidogrel, etc.), and history of diabetes and Ethics Committee of our hospital (No. 2017011021), and hypertension. (2) Te results of clinical examination, all the included patients had signed written informed including fasting blood glucose (FPG), triglyceride (TG), consent. total (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDLC), Patients apolipoprotein A1 (Apo A1), apolipoprotein B (Apo B), Te patients who underwent coronary angiography lipoprotein a (LP-a), glycated haemoglobin. (3) Te PCI 1 year after PCI in our hospital from January 2017 to May details, including the reasons for stent implantation, 2019 were selected as the potential research subjects. All which was divided into stable angina, unstable angina, patients underwent PCI due to coronary artery steno- and acute . Te number of coronary sis > 75%. Te included patients were: adult patients with artery lesion. Te details of stent implantation, including age > 18 years; it’s the frst time for stent implantation; the implantation position, which was divided into left ante- patients were well-informed and agree to participant in rior descending artery, left circumfex artery and right this study. Te exclusion criteria were: Patients who were coronary artery, the stent length (≤ 20 mm or > 20 mm), not implanted for the frst time or had coronary artery stent diameter (< 3 mm or ≥ 3 mm). Regular taking anti- bypass grafting; patients with malignant tumors, autoim- drugs after surgery was defned as regular oral mune diseases, and severe liver and kidney dysfunction; administration of aspirin or clopidogrel after operation, patients with cardiomyopathy, congenital heart disease, and any one or both of them shouldn’t be discontinued and valvular disease; patients who did not willing to par- for more than 3 days. ticipant in this study. Statistical analysis Interventions All of the statistical analyses were conducted using SPSS All patients received conventional treatment for coro- 23.0 (SPSS Inc., Chicago, USA). Categorical variables nary heart disease, including reasonable diet, body were analyzed using the χ2 test or Fisher’s exact test, and weight control, smoking and alcohol cessation, moderate continuous variables were analyzed using Student’s t test. Wang et al. BMC Cardiovasc Disord (2020) 20:510 Page 3 of 6

Multivariate logistic regression analyses were performed The results of clinical examination of included patients using the forward likelihood ratio selection method to As Table 2 presented, the LDL-C in ISR groups was sig- identify independent risk factors. All the P values were nifcantly higher than that of no-ISR group (p = 0.048), two-tailed, and p < 0.05 was considered as being statisti- there were no signifcant diferences between two groups cally signifcant. in FPG, TG, TC, HDL-C, Apo A1, Apo B, LP-a and gly- cated haemoglobin level (all p > 0.05). Results The characteristics of included patients A total of 209 patients were included, of which 64 Logistic multi‑factor regression analysis patients were diagnosed as ISR, the incidence of ISR was Table 3 indicated the assignment of logistic regression 30.62%. as Table 1 presented, there were signifcant dif- analysis. As Table 4 showed, the hypertension (OR 4.30, ferences on the hypertension, diabetes, number of coro- 95% CI 1.12–9.34), diabetes (OR 5.29, 95% CI 1.25–9.01), nary artery lesions, reasons for stent implantation, the number of coronary artery lesions ≥ 2 (OR 4.84, 95% CI diameter of stent, the length of stent and stent position 1.21–9.55), LDL-C ≥ 1.9 mmol/L (OR 5.93, 95% CI 2.29– between ISR group and no-ISR group (all p < 0.05). But 10.01), unstable angina (OR 2.92, 95% CI 1.20–4.55), left no signifcant diference on the gender, age, history of anterior descending artery (OR 4.01, 95% CI 1.73–7.58), smoke and drinking, number of implanted stents, and diameter of stent ≥ 3 mm (OR 5.42, 95% CI 1.24–10.84), antiplatelet drugs regularly taking between two groups the length of stent > 20 mm (OR 3.06, 95% CI 1.19–5.22) were found (all p > 0.05). were independent risk factor for ISR (all p < 0.05).

Table 1 The characteristics of included patients Variables ISR group (n 64) No-ISR group (n 145) t/χ2 p = = Male/female 42/22 97/48 1.204 0.117 Age (years) 65.39 8.91 64.04 9.12 7.226 0.052 ± ± Hypertension 43 (67.19%) 55 (37.93%) 1.127 0.009 Diabetes 36 (56.25%) 59 (40.69%) 1.014 0.037 History of smoke 22 (34.38%) 49 (33.79%) 1.205 0.089 History of drinking 19 (29.69%) 40 (27.59%) 1.184 0.092 Number of coronary artery lesions One artery 25 (39.06%) 96 (66.21%) 1.947 0.022 Two arteries 24 (37.50%) 44 (30.34%) Three arteries 15 (23.44%) 5 (3.45%) Reasons for stent implantation Stable angina 12 (18.75%) 25 (17.24%) 1.374 0.016 Unstable angina 36 (56.25%) 44 (30.34%) Acute myocardial infarction 16 (25%) 76 (52.42%) Number of implanted stents (n) 2.31 1.05 2.01 1.10 1.294 0.117 ± ± The diameter of stent < 3 mm 38 (59.38%) 61 (42.07%) 1.331 0.028 3 mm 26 (40.62%) 84 (57.93%) ≥ The length of stent 20 mm 4 (6.25%) 58 (40%) 1.097 0.034 ≤ > 20 mm 60 (93.75%) 87 (60%) Stent position Left anterior descending artery 36 (56.25%) 54 (37.24%) 1.164 0.027 Left circumfex artery 8 (12.50%) 32 (22.07%) Right coronary artery 20 (31.25%) 59 (40.69%) Take antiplatelet drugs regularly 37 (57.81%) 80 (55.17%) 1.089 0.085 Wang et al. BMC Cardiovasc Disord (2020) 20:510 Page 4 of 6

Table 2 The results of clinical examination of included patients Variables ISR group (n 64) No-ISR group (n 145) T p = = FPG (mmol/L) 7.19 2.05 6.79 2.12 1.275 0.093 ± ± TG (mmol/L) 1.54 1.02 1.64 1.07 1.460 0.106 ± ± TC (mmol/L) 4.36 0.92 3.41 0.99 1.204 0.053 ± ± LDL-C (mmol/L) 2.58 0.41 2.01 0.33 1.129 0.048 ± ± HDL-C (mmol/L) 1.03 0.27 1.02 0.21 1.044 0.117 ± ± Apo A1 (g/L) 0.95 0.21 0.96 0.18 1.940 0.325 ± ± Apo B (g/L) 0.72 0.14 0.70 0.13 1.282 0.113 ± ± LP-a (mg/L) 224.73 59.83 232.05 64.11 18.405 0.126 ± ± Glycated haemoglobin (%) 5.85 0.74 5.66 0.62 1.204 0.094 ± ±

Table 3 The assignment of logistic multi-factor regression conducted based on those factors. PCI is currently the analysis main efective treatment option for CHD, especially Variables Assignment drug-coated stents have greatly improved the efcacy and prognosis of patients with CHD [10]. Although drug- Hypertension Yes 1, no 0 = = coated stents can signifcantly reduce the risk of ISR, the Diabetes Yes 1, no 0 = = risk of acute heart disease events such as progressive LDL-C (mmol/L) 1.9 mmol/L 1, < 1.9 mmol/L 0 ≥ = = angina or acute myocardial infarction caused by ISR still Number of coronary artery lesions 2 arteries 1, 1 artery 0 ≥ = = exists, which seriously afects the outcome after PCI [11]. Reasons for stent implantation Unstable angina 1, other rea- sons 0 = ISR is the formation of endometrial hyperplasia mediated = by biological, mechanical, technical and complex factors Stent position Left anterior descending artery 1, left circumfex artery 0 = related to the patient, which will lead to the loss of tar- = The diameter of stent 3 mm 1, < 3 mm 0 get blood vessels and increase heart disease events [12]. ≥ = = The length of stent > 20 mm 1, 20 mm 0 Terefore, early recognition and prevention of ISR is par- = ≤ = ticularly important. Diabetes and hypertension patients have relatively complicated vascular lesions and unstable endothelial Table 4 The results of logistic multi-factor regression analysis function [13]. Terefore, during PCI treatment, coronary intimal tear or dissection is more likely to occur, which Factors β Sx OR 95%CI p promotes platelet adhesion [14]. Besides, glucose can also Hypertension 0.83 0.22 4.30 1.12–9.34 0.035 directly damage coronary endothelial cells, these factors Diabetes 0.96 0.33 5.29 1.25–9.01 0.029 increase the incidence of ISR [15]. Unbalanced glucose Number of coronary artery 0.88 0.21 4.84 1.21–9.55 0.024 metabolism activates vascular endothelial infammation, lesions 2 arteries which is a risk factor for the formation of coronary ather- ≥ LDL-C 1.9 mmol/L 0.79 0.25 5.93 2.29–10.01 0.016 osclerotic plaques [16]. Te patient’s poor blood glucose ≥ Unstable angina 0.59 0.18 2.92 1.20–4.55 0.037 control after stenting will aggravate the process of pro- Left anterior descending artery 0.77 0.29 4.01 1.73–7.58 0.044 tein glycosylation and oxidation, damaging the vascular Diameter of stent 3 mm 0.96 0.32 5.42 1.24–10.84 0.038 endothelium and initiate atherosclerotic plaque, which ≥ The length of stent > 20 mm 0.79 0.24 3.06 1.19–5.22 0.023 is related to ISR [17]. Hypertension is a risk factor for CHD. When the blood pressure fuctuates or continues to be under high pressure, the blood accelerates the shear Discussions force on the tube wall, damages the vascular endothelial Te mechanism of ISR has not been fully elucidated, cells [18], and increases the incidence of ISR. Terefore, the results of study have found that the hypertension, patients with hypertension must strictly control blood pressure after surgery. For patients with a history of dia- diabetes, number of coronary artery lesions ≥ 2 arter- ies, LDL-C 1.9 mmol/L, unstable angina, left anterior betes or hypertension, strictly controlling blood pressure ≥ and sugar is benefcial to reduce the risk of ISR. descending artery, diameter of stent ≥ 3 mm, the length of stent > 20 mm were independent risk factors for ISR High LDL-C is an important risk factor for CHD [19]. in patients with PCI, targeted preventions should be High levels of LDL-C stimulate infammation, damage Wang et al. BMC Cardiovasc Disord (2020) 20:510 Page 5 of 6

vascular endothelial cells, and promote the deposi- patient’s treatment. Secondly, the sample size was small, it tion of cholesterol in the wall [20]. It’s been might be not power enough to detect the potential related reported that controlling cholesterol intake can reduce risk factors, more studies on the risk factors for the ISR are the incidence of CHD [21]. Terefore, standardizing needed in the future. Finally, we only made a follow-up for medication after PCI is very important. Intensifed statin one year, and we did not have any died patients, the long- therapy after PCI to reduce LDL-C levels is benefcial to term follow-up with diferent time intervals are needed in reduce the neointimal hyperplasia [22]. Previous study the future. [23] has reported that the LDL-C level of patients was signifcantly correlated with ISR, which is consistent with Conclusions our fndings. Long-term oral lipid-lowering drugs may In conclusion, for patients with PCI, the hypertension, be required after PCI, and LDL-C should be controlled diabetes, number of coronary artery lesions ≥ 2 arter- under 1.9 mmol/L. ies, LDL-C ≥ 1.9 mmol/L, unstable angina, left anterior Studies [24] have reported that the incidence of ISR descending artery, diameter of stent ≥ 3 mm, the length of of anterior descending branch is signifcantly higher. stent > 20 mm are independent risk factors for ISR, inter- And the incidence of ISR in the left anterior descending ventions targeted on those risk factors are warranted to branch is signifcantly higher than that of left circumfex prevent the ISR. branch and the right coronary artery. ISR is more likely to occur in those with thinner vascular [25]. Terefore, for Abbreviations anterior descending branch lesions or complex lesions, it CHD: Coronary heart disease; PCI: Percutaneous coronary intervention; ISR: is necessary to strictly understand the PCI surgical indi- Intra-stent restenosis; FPG: Fasting blood glucose; TG: Triglyceride; TC: Total cholesterol; LDL-C: Low density lipoprotein cholesterol; HDLC: High density cations, and use intravascular ultrasound and other vas- lipoprotein cholesterol; Apo A1: Apolipoprotein A1; Apo B: Apolipoprotein B; cular imaging techniques to optimize the surgical plan. LP-a: Lipoprotein a. Te ISR is closely associated with the damage to the Acknowledgements intima, which induces intimal hyperplasia, causing loss of Not applicable. the lumen over time [26]. In the process of PCI treatment, whether it is the caused by balloon expansion to Authors’ contributions PW designed research; PW, HQ and RW conducted research; PW, RH analyzed the intima or the mechanical stimulation generated by data; PW and JG wrote the frst draft of manuscript; PW had primary responsi- the stent, it may exert an activation efect on infam- bility for fnal content. All authors read and approved the fnal manuscript. matory factors, induce local infammation, and then Funding stimulate smooth muscle cells [27, 28]. Te proliferation Not applicable. reaction also causes a certain deposition of extracellular matrix, resulting in thickening of the intima and ISR [29]. Availability of data and materials All data generated or analyzed during this study are included in this published Some doctors [30] have pointed out that both the diam- article, the datasets used and analyzed during the current study are available eter of the blood vessel and the length of the stent have from the corresponding author on reasonable request. a certain correlation with the ISR. Arteries with smaller Ethics approval and consent to participate diameters are relatively weak in their ability to adapt to This study was reviewed and approved by the Medical Ethics Committee of neointimal proliferation into the lumen [31]. Te thin- Afliated Hospital of Chengde Medical College (No. 2017011021), and all the ner blood vessels are implanted with stents and the blood included patients had signed written informed consent. fow rate is slower, and ISR is more likely to occur after Consent for publication PCI. Multiple stents need to be implanted due to difuse Not applicable. lesions [32]. Te total area of the stent metal material in Competing interests contact with the blood vessel wall is large, which stimu- The authors declare that they have no competing interests. lates vascular endothelial hyperplasia and plaque forma- tion, increasing the risk of ISR [33]. Tis study has found Author details 1 Department of Cardiology, Afliated Hospital of Chengde Medical College, that stent diameter < 3 mm and stent length > 20 mm are No. 36 Nanyingzi Street, Chengde 067000, Hebei Province, People’s Republic risk factors for ISR, suggesting the importance of opti- of China. 2 Department of Cardiology, Chengde Central Hospital, Chengde, mizing PCI. For small vessel disease or difuse disease, People’s Republic of China. precisely guide the stent placement and reduce the num- Received: 3 August 2020 Accepted: 24 November 2020 ber of stents is necessary to reduce the incidence of ISR. Several limitations must be concerned in this study, future studies with larger sample size and longer follow-up are needed. Firstly, since this study is a retrospective design, there might be some bias and heterogeneity between the Wang et al. BMC Cardiovasc Disord (2020) 20:510 Page 6 of 6

References 18. Holmberg J, Bhattachariya A, Alajbegovic A, Rippe C, Ekman M, Dahan 1. Hoole SP, Bambrough P. Recent advances in percutaneous coronary D, Hien TT, Boettger T, Braun T, Sward K, et al. Loss of vascular myogenic intervention. Heart. 2020;106(16):1380–6. tone in miR-143/145 knockout mice is associated with hypertension- 2. Alexander JH, Wojdyla D, Vora AN, Thomas L, Granger CB, Goodman SG, induced vascular lesions in small mesenteric arteries. Arterioscler Thromb Aronson R, Windecker S, Mehran R, Lopes RD. Risk/beneft tradeof of Vasc Biol. 2018;38(2):414–24. antithrombotic therapy in patients with atrial fbrillation early and late 19. Peng J, Luo F, Ruan G, Peng R, Li X. Hypertriglyceridemia and atheroscle- after an acute coronary syndrome or percutaneous coronary interven- rosis. Lipids Health Dis. 2017;16(1):233. tion: insights from AUGUSTUS. Circulation. 2020;141(20):1618–27. 20. Shiiba M, Zhang B, Miura SI, Ike A, Nose D, Kuwano T, Imaizumi S, Sugihara 3. Tan S, Ramzy J, Burgess S, Zaman S. Percutaneous coronary interven- M, Iwata A, Nishikawa H, et al. Association between discordance of LDL-C tion for coronary bifurcation lesions: latest evidence. Curr Treat Options and non-HDL-C and clinical outcomes in patients with stent implanta- Cardiovasc Med. 2020;22(2):6. tion: from the FU-Registry. Heart Vessels. 2018;33(2):102–12. 4. Guo L, Lv HC, Huang RC. Percutaneous coronary intervention in elderly 21. Zhong Z, Hou J, Zhang Q, Zhong W, Li B, Li C, Liu Z, Yang M, Zhao P. patients with coronary chronic total occlusions: current evidence and Assessment of the LDL-C/HDL-C ratio as a predictor of one year clinical future perspectives. Clin Interv Aging. 2020;15:771–81. outcomes in patients with acute coronary syndromes after percutaneous 5. Murata N, Takayama T, Hiro T, Hirayama A. Balloon pin-hole rupture dur- coronary intervention and drug-eluting stent implantation. Lipids Health ing percutaneous coronary intervention for recurrent, calcifed in-stent Dis. 2019;18(1):40. restenosis: a case report. Catheter Cardiovasc Interv. 2018;91(7):1287–90. 22. Kotani K, Sekine Y, Ishikawa S, Ikpot IZ, Suzuki K, Remaley AT. High- 6. Yu Y, Zhou Y, Ma Q, Jia S, Wu S, Sun Y, Liu X, Zhao Y, Liu Y, Shi D. The conical density lipoprotein and prostate cancer: an overview. J Epidemiol. stent in coronary artery improves hemodynamics compared with the 2013;23(5):313–9. traditional cylindrical stent. Int J Cardiol. 2017;227:166–71. 23. Huang A, Qi X, Wei L, Zhang M, Zhou S. Non-HDL-c/TC: a novel lipid- 7. Alfonso F, Perez-Vizcayno MJ, Cuesta J, Garcia Del Blanco B, Garcia- related marker in the assessment of severity of coronary artery lesions Touchard A, Lopez-Minguez JR, Masotti M, Zueco J, Cequier A, Velazquez and cardiovascular outcomes. Cardiol Res Pract. 2019;2019:5931975. M, et al. 3-year clinical follow-up of the RIBS IV clinical trial: a prospec- 24. Si D, Tong Y, Yu B, He Y, Liu G. In-stent restenosis and longitudinal stent tive randomized study of drug-eluting balloons versus everolimus- deformation: a case report. BMC Cardiovasc Disord. 2020;20(1):24. eluting stents in patients with in-stent restenosis in 25. Kaihara T, Higuma T, Kotoku N, Kuwata S, Mitarai T, Koga M, Kamijima R, previously treated with drug-eluting stents. JACC Cardiovasc Interv. Izumo M, Ishibashi Y, Tanabe Y, et al. Calcifed nodule protruding into the 2018;11(10):981–91. lumen through stent struts: an in-vivo OCT analysis. Cardiovasc Revasc 8. Picard F, Doucet S, Asgar AW. Contemporary use of drug-coated balloons Med. 2020. https​://doi.org/10.1016/j.carre​v.2020.03.015. in coronary artery disease: where are we now? Arch Cardiovasc Dis. 26. Shiraishi J, Koshi N, Matsubara Y, Nishimura T, Shikuma A, Shoji K, Ito D, 2017;110(4):259–72. Kimura M, Kishita E, Nakagawa Y, et al. Stent-less percutaneous coronary 9. Alfonso F, Cequier A, Angel J, Marti V, Zueco J, Bethencourt A, Mantilla R, intervention using rotational atherectomy and drug-coated balloon: a Lopez-Minguez JR, Gomez-Recio M, Moris C, et al. Value of the American case series and a mini review. Cardiovasc Revasc Med. 2018;19(6):705–11. College of Cardiology/American Heart Association angiographic classif- 27. Huang WC, Teng HI, Chen HY, Wu CJ, Tsai CT, Hsueh CH, Chen YY, Hau WK, cation of coronary lesion morphology in patients with in-stent restenosis. Lu TM. Association between asymmetric dimethylarginine and in-stent Insights from the Restenosis Intra-stent Balloon versus elec- restenosis tissue characteristics assessed by optical coherence tomogra- tive Stenting (RIBS) randomized trial. Am Heart J. 2006;151(3):e681–9. phy. Int J Cardiol. 2019;289:131–7. 10. Alfonso F, Perez-Vizcayno MJ, Garcia Del Blanco B, Garcia-Touchard A, 28. Su X, Wang A, Zhu H, Su H, Duan Y, Wu S, Zhang M, Huang Y, Zhou X, Lopez-Minguez JR, Masotti M, Zueco J, Melgares R, Mainar V, Moreno R, Cao Y. Acute myocardial infarction and transient elevated anticardiolipin et al. Everolimus-eluting stents in patients with bare-metal and drug- antibody in a young adult with possible familial hypercholesterolemia: eluting in-stent restenosis: results from a patient-level pooled analysis of a case report : anticardiolipin antibody and myocardial infarction. BMC the RIBS IV and V trials. Circ Cardiovasc Interv. 2016;9(7):003479. Cardiovasc Disord. 2019;19(1):156. 11. Alfonso F, Perez-Vizcayno MJ, Garcia Del Blanco B, Otaegui I, Masotti M, 29. Nestelberger T, Jeger R. Drug-coated balloons for small coronary vessel Zueco J, Velaquez M, Sanchis J, Garcia-Touchard A, Lazaro-Garcia R, et al. interventions: a literature review. Interv Cardiol. 2019;14(3):131–6. Long-term results of everolimus-eluting stents versus drug-eluting bal- 30. Gray WA, Jaf MR, Parikh SA, Ansel GM, Brodmann M, Krishnan P, Razavi loons in patients with bare-metal in-stent restenosis: 3-year follow-up of MK, Vermassen F, Zeller T, White R, et al. Mortality assessment of pacli- the RIBS V clinical trial. JACC Cardiovasc Interv. 2016;9(12):1246–55. taxel-coated balloons: patient-level meta-analysis of the ILLUMENATE 12. Hong L, Wang H, Yin QL, Li LF, Lai HL, Chen ZQ, Lu LX, Li B, Huang Q. clinical program at 3 years. Circulation. 2019;140(14):1145–55. Percutaneous coronary intervention of patients with complex small coro- 31. Feng W, Wang J, Yan X, Zhai C, Shi W, Wang Q, Zhang Q, Li M. nary artery lesion unsuitable for coronary artery bypass graft. Zhonghua alleviates monocrotaline-induced pulmonary arterial hypertension via Yi Xue Za Zhi. 2010;90(2):107–9. inhibition of FoxO1-mediated autophagy. Naunyn Schmiedebergs Arch 13. Geraldes R, Jurynczyk M, Dos Passos G, Prichler A, Chung K, Hagens M, Pharmacol. 2019;392(5):605–13. Ruggieri S, Huerga E, Sastre-Garriga J, Enzinger C, et al. Distinct infuence 32. Mohiaddin H, Wong T, Burke-Gafney A, Bogle RG. Drug-coated of diferent vascular risk factors on white matter brain lesions in multiple balloon-only percutaneous coronary intervention for the treatment sclerosis. J Neurol Neurosurg Psychiatry. 2020;91(4):388–91. of de novo coronary artery disease: a systematic review. Cardiol Ther. 14. Maor GS, Faden MS, Brown R. Prevalence, risk factors and pregnancy out- 2018;7(2):127–49. comes of women with vascular brain lesions in pregnancy. Arch Gynecol 33. Alfonso F, Sandoval J, Perez-Vizcayno MJ, Cardenas A, Gonzalo N, Obstet. 2020;301(3):665–70. Jimenez-Quevedo P, Ibanez B, Nunez-Gil I, Rivero F, Escaned J, et al. 15. Ferraro RA, van Rosendael AR, Lu Y, Andreini D, Al-Mallah MH, Cademar- Mechanisms of balloon angioplasty and repeat stenting in patients with tiri F, Chinnaiyan K, Chow BJW, Conte E, Cury RC, et al. Non-obstructive drug-eluting in-stent restenosis. Int J Cardiol. 2015;178:213–20. high-risk plaques increase the risk of future culprit lesions comparable to obstructive plaques without high-risk features: the ICONIC study. Eur Heart J Cardiovasc Imaging. 2020;21(9):973–80. Publisher’s Note 16. Yahagi K, Kolodgie FD, Lutter C, Mori H, Romero ME, Finn AV, Virmani R. Springer Nature remains neutral with regard to jurisdictional claims in pub- Pathology of human coronary and carotid artery and lished maps and institutional afliations. vascular calcifcation in diabetes mellitus. Arterioscler Thromb Vasc Biol. 2017;37(2):191–204. 17. Song B, Kim D, Nguyen NH, Roy S. Inhibition of diabetes-induced lysyl oxidase overexpression prevents retinal vascular lesions associated with diabetic retinopathy. Investig Ophthalmol Vis Sci. 2018;59(15):5965–72.