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摘要: 目的 探究冠心病患者经皮冠状动脉介入治疗(PCI)后支架内再狭窄(ISR)的危险因素，以及磷脂和鞘磷脂代谢差异与ISR的关系。方法 纳入2017年1月—2020年12月在北京安贞医院进行首次PCI手术的冠心病患者共412例，根据PCI术后1年是否发生ISR分为ISR组(35例)和非ISR组(377例)。运用液相色谱串联质谱(LC-MS/MS)技术分析比对两组患者血液样本的代谢产物差异。采用多因素logistic回归分析筛选冠心病患者PCI后ISR的危险因素。结果 非ISR组与ISR组在高密度脂蛋白胆固醇(HDL-C)、血管病变数量、病变长度、支架内径、支架长度、后扩直径方面均差异有统计学意义(均P < 0.05)。多因素logistic回归分析及代谢组学分析结果显示，非ISR组与ISR组患者血液代谢产物存在显著差异，主要为磷脂及鞘磷脂类代谢物的差异(均P < 0.05)。结论 HDL-C、病变长度、支架内径及支架长度为冠心病患者PCI后ISR的影响因素，同时磷脂及鞘磷脂类代谢物在预测ISR的发生方面可能发挥着重要作用。Abstract: Objective To investigate the risk factors for in-stent restenosis(ISR) after percutaneous coronary intervention(PCI) in patients with coronary heart disease, and the relationship between differences in phospholipid and sphingolipid metabolism with ISR.Methods A total of 412 patients with coronary heart disease who underwent their first PCI at Beijing Anzhen Hospital from January 2017 to December 2020 were included, and all patients were divided into the ISR group(n=35) and the non-ISR group(n=377) according to whether ISR occurred within 1 year after PCI. The differences in metabolites of patients' blood samples between the two groups were analyzed using liquid chromatography tandem mass spectrometry(LC-MS/MS). Multi-factor logistic regression was used to analyze the risk factors for ISR after PCI in patients with coronary heart disease.Results There were significant differences in high-density lipoprotein cholesterol(HDL-C), number of vascular lesions, lesion length, stent inner diameter, stent length, and post-dilation diameter between the ISR group and the non-ISR group(all P < 0.05). Multi-factor logistic regression analysis and metabolomic analysis showed that there were significant differences in blood metabolites between the two groups, mainly the differences in phospholipids and sphingomyelin metabolites (all P < 0.05).Conclusion HDL-C, lesion length, stent inner diameter, and stent length are influencing factors of ISR after PCI in patients with coronary heart disease, and phospholipids and sphingolipid metabolites may play an important role in predicting the occurrence of ISR.
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Key words:
- percutaneous coronary intervention /
- in-stent restenosis /
- metabolomics /
- phospholipids /
- sphingomyelin
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图 1 ISR组和非ISR组血液代谢产物的PLS-DA分析结果
Figure 1. Blood metabolites in non-ISR group and ISR group showed by PLS-DA analysis
图 2 VIP分析显示的ISR组和非ISR组具有显著差异的代谢产物
Figure 2. Significantly different metabolites between non-ISR group and ISR group showed by VIP analysis
表 1 非ISR组与ISR组基础资料比较
Table 1. Comparison of baseline data between non-ISR group and ISR group
例(%), X±S 项目 非ISR组(377例) ISR组(35例) P 男/女/例 287/90 24/11 0.320 年龄/岁 57.46±9.38 59.29±7.48 0.265 体重指数/(kg·m-2) 25.84±3.28 26.59±3.46 0.197 高血压 121(32.10) 7(20.00) 0.139 糖尿病 117(31.03) 13(37.14) 0.457 吸烟史 205(54.38) 18(51.43) 0.738 饮酒史 128(33.95) 14(40.00) 0.471 HDL-C/(mmol·L-1) 1.26±0.25 1.17±0.28 0.035 LDL-C/(mmol·L-1) 2.48±0.66 2.65±0.58 0.128 TG/(mmol·L-1) 1.22±0.71 1.40±0.67 0.147 hs-CRP/(mg·L-1) 1.11±1.19 1.35±0.96 0.256 CREA/(μmol·L-1) 70.81±15.13 67.39±14.06 0.200 HbA1c/% 6.40±1.21 6.63±1.54 0.313 WBC/(×109·L-1) 6.96±1.89 6.98±1.56 0.967 RBC/(×1012·L-1) 4.76±0.46 4.66±0.48 0.212 病变情况 0.024 单支病变 98(25.99) 5(14.29) 双支病变 141(37.40) 9(25.71) 多支病变 138(36.60) 21(60.00) 病变长度/mm 12.00±5.30 14.81±6.56 0.003 支架数目/个 1.40±0.69 1.49±0.61 0.478 支架内径/mm 2.99±0.46 2.75±0.35 0.002 支架长度/mm 15.38±8.32 18.51±8.20 0.034 预扩直径/mm 2.54±0.41 2.43±0.31 0.127 后扩直径/mm 3.19±0.49 3.02±0.43 0.045 
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表 2 ISR组和非ISR组差异性代谢产物
Table 2. Differential metabolites in ISR and non-ISR patients
差异代谢物 VIP P值 变化趋势 PC(36：0) 1.789 0.016 升高 PE(36：2) 1.742 0.021 下降 PG(34：1) 1.729 0.047 下降 PC(16：0/18：2) 1.720 0.027 升高 PE(32：1) 1.711 0.028 下降 PI(36：4) 1.707 0.032 下降 PI(34：1) 1.674 0.019 下降 SM(d18：1/20：2) 1.653 0.025 下降
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表 3 ISR危险因素的logistic分析
Table 3. Logistic analysis of risk factors for ISR
危险因素 OR 95%CI P PC(36：0) 2.94 2.41~3.22 < 0.001 PC(16：0/18：2) 1.28 1.17~1.65 0.010 PE(36：2) 0.42 0.38~0.59 < 0.001 PI(36：4) 0.51 0.34~0.68 0.017 SM(d18：1/20：2) 0.72 0.58~0.82 0.038
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