心外膜脂肪组织对经皮冠状动脉介入术后支架内再狭窄的影响

doi:10.12114/j.issn.1007-9572.2022.0453

摘要/Abstract

摘要： 经皮冠状动脉介入术是冠心病的主要治疗手段，可有效提高患者的生存率，但随之而来的支架内再狭窄成为心血管领域的新难题。炎症和血管内皮功能障碍是支架内再狭窄的始动因素，在此基础上出现的新生内膜增厚和新生动脉粥样硬化共同加速了支架内再狭窄的进展。心外膜脂肪组织分泌的炎性因子可直接影响冠状动脉血管内皮细胞、平滑肌细胞和巨噬细胞功能，破坏冠状动脉血管壁的稳态，从而参与冠状动脉支架置入术后支架内再狭窄的病理生理过程。此外，多项临床研究表明心外膜脂肪组织对冠心病患者经皮冠状动脉介入术后1年内支架内再狭窄的发生有一定预测作用。因此，本文就近年来心外膜脂肪组织对经皮冠状动脉介入术后支架内再狭窄影响的研究进展、心外膜脂肪预测支架内再狭窄的临床研究进展，以及支架内再狭窄的治疗进展进行综述，以期为支架内再狭窄的预防和治疗提供新思路。

关键词: 经皮冠状动脉介入治疗, 支架内再狭窄, 药物洗脱支架, 心外膜脂肪组织, 冠心病

Abstract:

As a major treatment for coronary artery disease, percutaneous coronary intervention (PCI) effectively enhances the survival rate of patients. However, the post-PCI in-stent restenosis has become a new cardiovascular problem that is difficult to solve. Inflammation and endothelial dysfunction, as the initiating inducing factors of in-stent restenosis, together with subsequently developed neointimal thickening and neoatherosclerosis based on which, promote the progression of in-stent restenosis. Inflammatory markers secreted by epicardial adipose tissue may directly influence the function of coronary vascular endothelial cells, smooth muscle cells and macrophages, disrupting the homeostasis of the coronary vessel wall, thereby being involved in the pathophysiological process of in-stent restenosis after coronary stenting. In addition, multiple clinical studies have shown that epicardial adipose tissue could partially predict in-stent restenosis in patients with coronary artery disease within 1 year after PCI. We reviewed the latest advances in the effect of epicardial adipose tissue on in-stent restenosis after PCI, and clinical prediction of post-PCI in-stent restenosis by epicardial fat, as well as treatment for post-PCI in-stent restenosis, providing a new idea for the prevention and treatment of post-PCI in-stent restenosis.

Key words: Percutaneous coronary intervention, In-stent restenosis, Drug-eluting stents, Epicardial adipose tissue, Coronary disease

安景景,王小娟,邓爱云. 心外膜脂肪组织对经皮冠状动脉介入术后支架内再狭窄的影响[J]. 中国全科医学, 2023, 26(09): 1146-1150. DOI: 10.12114/j.issn.1007-9572.2022.0453.
AN Jingjing,WANG Xiaojuan,DENG Aiyun. Effect of Epicardial Adipose Tissue on In-stent Restenosis after Percutaneous Coronary Intervention: a Review[J]. Chinese General Practice, 2023, 26(09): 1146-1150. DOI: 10.12114/j.issn.1007-9572.2022.0453.

图/表 1

参考文献 34

[1]	MOUSSA I D, MOHANANEY D, SAUCEDO J，et al. Trends and outcomes of restenosis after coronary stent implantation in the United States[J]. J Am Coll Cardiol，2020，76(13):1521-1531. DOI：10.1016/j.jacc.2020.08.002.
[2]	LANSKY A, GRUBMAN D, SCHELLER B. Paclitaxel-coated balloons：a safe alternative to drug-eluting stents for coronary in-stent restenosis[J]. Eur Heart J，2020，41(38):3729-3731. DOI：10.1093/eurheartj/ehz731.
[3]	KONWERSKI M, GASECKA A, OPOLSKI G，et al. Role of epicardial adipose tissue in cardiovascular diseases：a review[J]. Biology （Basel），2022，11(3):355. DOI：10.3390/biology11030355.
[4]	IACOBELLIS G, BARONI M G. Cardiovascular risk reduction throughout GLP-1 receptor agonist and SGLT2 inhibitor modulation of epicardial fat[J]. J Endocrinol Invest，2022，45(3):489-495. DOI：10.1007/s40618-021-01687-1.
[5]	SOEHNLEIN O, LIBBY P. Targeting inflammation in atherosclerosis - from experimental insights to the clinic[J]. Nat Rev Drug Discov，2021，20(8):589-610. DOI：10.1038/s41573-021-00198-1.
[6]	LYU N, DU Z Y, QIU H，et al. Mimicking the nitric oxide-releasing and glycocalyx functions of endothelium on vascular stent surfaces[J]. Adv Sci （Weinh），2021，21(7) . DOI：10.1002/advs.202002330.
[7]	NYAWO T A, PHEIFFER C, MAZIBUKO-MBEJE S E，et al. Physical exercise potentially targets epicardial adipose tissue to reduce cardiovascular disease risk in patients with metabolic diseases：oxidative stress and inflammation emerge as major therapeutic targets[J]. Antioxidants （Basel），2021，10(11):1758. DOI：10.3390/antiox10111758.
[8]	PAYNE G A, BORBOUSE L, KUMAR S，et al. Epicardial perivascular adipose-derived leptin exacerbates coronary endothelial dysfunction in metabolic syndrome via a protein kinase C-beta pathway[J]. Arterioscler Thromb Vasc Biol，2010，30(9):1711-1717. DOI：10.1161/ATVBAHA.110.210070.
[9]	AMAN P, KHANAL S. Leptin in atherosclerosis：focus on macrophages，endothelial and smooth muscle cells[J]. Int J Mol Sci，2021，22(11):5446. DOI：10.3390/ijms22115446.
[10]	NOBLET J N, OWEN M K, GOODWILL A G，et al. Lean and obese coronary perivascular adipose tissue impairs vasodilation via differential inhibition of vascular smooth muscle K⁺ channels[J]. Arterioscler Thromb Vasc Biol，2015，35(6):1393-1400. DOI：10.1161/ATVBAHA.115.305500.
[11]	ZHU X, ZHANG H W, CHEN H N，et al. Perivascular adipose tissue dysfunction aggravates adventitial remodeling in obese mini pigs via NLRP3 inflammasome/IL-1 signaling pathway[J]. Acta Pharmacol Sin，2019，40(1):46-54. DOI：10.1038/s41401-018-0068-9.
[12]	KASTL S P, KATSAROS K M, KRYCHTIUK K A，et al. The adipokine vaspin is associated with decreased coronary in-stent restenosis[J]. PLoS One，2020，15(5):e0232483. DOI：10.1371/journal.pone.0232483. eCollection 2020.
[13]	CHANG L, GARCIA-BARRIO M T, CHEN Y E. Perivascular adipose tissue regulates vascular function by targeting vascular smooth muscle cells[J]. Arterioscler Thromb Vasc Biol，2020，40(5):1094-1109. DOI：10.1161/ATVBAHA.120.312464.
[14]	ERTEN M. Visfatin as a promising marker of cardiometabolic risk[J]. Acta Cardiol Sin，2021，37(5):464-472. DOI：10.6515/ACS.202109_37(5).20210323B.
[15]	ROMACHO T, VALENCIA I, RAMOS-GONZÁLEZ M，et al. Visfatin/eNampt induces endothelial dysfunction in vivo：a role for toll-like receptor 4 and NLRP3 inflammasome[J]. Sci Rep，2020，10(1):5386. DOI：10.1038/s41598-020-62190-w.
[16]	JAKUBIAK G K, PAWLAS N, CIESLAR G，et al. Pathogenesis and clinical significance of in-stent restenosis in patients with diabetes[J]. Int J Environ Res Public Health，2021，18(22):11970. DOI：10.3390/ijerph182211970.
[17]	DANG Y X, CHEN X J, MA S W，et al. Association of pericoronary adipose tissue quality determined by dual-layer spectral detector CT with severity of coronary artery disease：a preliminary study[J]. Front Cardiovasc Med，2021，8:720127. DOI：10.3389/fcvm.2021.720127.
[18]	SOWKA A, DOBRZYN P. Role of perivascular adipose tissue-derived adiponectin in vascular homeostasis[J]. Cells，2021，10(6):1485. DOI：10.3390/cells10061485.
[19]	WANG G, CHEN J J, DENG W Y，et al. CTRP12 ameliorates atherosclerosis by promoting cholesterol efflux and inhibiting inflammatory response via the miR-155-5p/LXRα pathway[J]. Cell Death Dis，2021，12(3):254. DOI：10.1038/s41419-021-03544-8.
[20]	OGAWA H, OHASHI K, ITO M，et al. Adipolin/CTRP12 protects against pathological vascular remodelling through suppression of smooth muscle cell growth and macrophage inflammatory response[J]. Cardiovasc Res，2020，116(1):237-249. DOI：10.1093/cvr/cvz074.
[21]	NAKAMURA D, DOHI T, ISHIHARA T，et al. Predictors and outcomes of neoatherosclerosis in patients with in-stent restenosis[J]. EuroIntervention，2021，17(6):489-496. DOI：10.4244/EIJ-D-20-00539.
[22]	NUSCA A, VISCUSI M M, PICCIRILLO F，et al. In stent neo-atherosclerosis：pathophysiology，clinical implications，prevention，and therapeutic approaches[J]. Life （Basel），2022，12(3):393. DOI：10.3390/life12030393.
[23]	ZHANG D M, CHEN S L. Potential mechanisms of in-stent neointimal atherosclerotic plaque formation[J]. J Cardiovasc Pharmacol，2021，78(3):388-393. DOI：10.1097/FJC.0000000000001059.
[24]	侯小玲，付振虹，单冬凯，等. 心外膜脂肪组织与经皮冠状动脉介入治疗相关短期并发症的关系[J]. 中国介入心脏病学杂志，2020，28(5):241-246. DOI：10.3969/j.issn.1004-8812.2020.05.001.
[25]	周庆娜，林文华，敬锐，等. 心外膜脂肪组织容积及炎症因子对支架置入术后支架内再狭窄的预测价值[J]. 中华医学杂志，2019，99(47):3732-3736. DOI：10.3760/cma.j.issn.0376-2491.2019.47.011.
[26]	ZHOU Y, ZHANG H W, TIAN F，et al. Influence of increased epicardial adipose tissue volume on 1-year in-stent restenosis in patients who received coronary stent implantation[J]. J Geriatr Cardiol，2016，13(9):768-775. DOI：10.11909/j.issn.1671-5411.2016.09.012.
[27]	PARK J S, CHOI B J, CHOI S Y，et al. Echocardiographically measured epicardial fat predicts restenosis after coronary stenting[J]. Scand Cardiovasc J，2013，47(5):297-302. DOI：10.3109/14017431.2013.824604.
[28]	伍琼，罗喆，洪李锋. 心外膜脂肪垫厚度与冠脉支架内再狭窄的相关性分析[J]. 中国医师杂志，2019，21(3):379-382. DOI：10.3760/cma.j.issn.1008-1372.2019.03.015.
[29]	宋续茂，周少梅，徐莉莉. 心外膜脂肪组织容积及炎症因子对支架植入术后支架内再狭窄的预测价值[J]. 临床和实验医学杂志，2021，20(15):1607-1609. DOI：10.3969/j.issn.1671-4695.2021.15.011.
[30]	王雅，路玉李，张艳，等. 心外膜脂肪组织厚度对急性冠脉综合征合并糖尿病患者支架内再狭窄的预测价值[J]. 中国循证心血管医学杂志，2021，13(6):722-725. DOI：10.3969/j.issn.1674-4055.2021.06.20.
[31]	仝珊，叶丛，杨凯，等. 心外膜脂肪和血清分泌型卷曲相关蛋白5与老年冠心病支架内再狭窄的相关性[J]. 中华老年心脑血管病杂志，2021，23(7):680-683.
[32]	CABRERA-REGO J O, ESCOBAR-TORRES R A, PARRA-JIMÉNEZ J D，et al. Epicardial fat thickness correlates with coronary in-stent restenosis in patients with acute myocardial infarction[J]. Clin Investig Arterioscler，2019，31(2):49-55. DOI：10.1016/j.arteri.2018.11.002.
[33]	贾晓萌，侯应龙. 冠状动脉支架内再狭窄的治疗进展[J]. 心脏杂志，2022，34(3):344-347,351.
[34]	GIACOPPO D, ALFONSO F, XU B，et al. Paclitaxel-coated balloon angioplasty vs. drug-eluting stenting for the treatment of coronary in-stent restenosis：a comprehensive，collaborative，individual patient data meta-analysis of 10 randomized clinical trials （DAEDALUS study）[J]. Eur Heart J，2020，41(38):3715-3728. DOI：10.1093/eurheartj/ehz594.

第一作者	样本量（例）	分组（例）		观察指标	试验结果^a
第一作者	样本量（例）	ISR组	NISR组	观察指标	试验结果^a
周庆娜^[25]	407	52	355	EAT体积	OR=1.003，95%CI（0.992，1.015），P=0.048
ZHOU^[26]	364	46	318	EAT体积	OR=1.009，95%CI（1.002，1.016），P=0.009
PARK^[27]	407	100	307	EAT厚度	OR=1.190，95%CI（1.010，1.330），P=0.007
伍琼^[28]	617	74	543	EAT厚度	OR=0.001，95%CI（0.000，0.118），P=0.004
宋续茂^[29]	96	21	75	EAT体积	OR=2.962，95%CI（1.531，5.371），P<0.001
王雅^[30]	84	13	71	EAT厚度	OR=9.970，95%CI（1.433，69.362），P=0.020
仝珊^[31]	408	62	346	EAT厚度	HR=0.492，95%CI（0.125，0.688），P=0.029
仝珊^[31]	408	62	346	EAT体积	HR=0.557，95%CI（0.192，0.782），P=0.004
CABRERA-REGO等^[32]	129	21	108	EAT厚度	OR=1.380，95%CI（1.010，2.190），P=0.029

第一作者	样本量（例）	分组（例）		观察指标	试验结果^a
第一作者	样本量（例）	ISR组	NISR组	观察指标	试验结果^a
周庆娜^[25]	407	52	355	EAT体积	OR=1.003，95%CI（0.992，1.015），P=0.048
ZHOU^[26]	364	46	318	EAT体积	OR=1.009，95%CI（1.002，1.016），P=0.009
PARK^[27]	407	100	307	EAT厚度	OR=1.190，95%CI（1.010，1.330），P=0.007
伍琼^[28]	617	74	543	EAT厚度	OR=0.001，95%CI（0.000，0.118），P=0.004
宋续茂^[29]	96	21	75	EAT体积	OR=2.962，95%CI（1.531，5.371），P<0.001
王雅^[30]	84	13	71	EAT厚度	OR=9.970，95%CI（1.433，69.362），P=0.020
仝珊^[31]	408	62	346	EAT厚度	HR=0.492，95%CI（0.125，0.688），P=0.029
仝珊^[31]	408	62	346	EAT体积	HR=0.557，95%CI（0.192，0.782），P=0.004
CABRERA-REGO等^[32]	129	21	108	EAT厚度	OR=1.380，95%CI（1.010，2.190），P=0.029