Incidence and predictors of calcified plaque in stents in patients with restenosis after drug-eluting stents
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摘要: 目的 本研究旨在探索药物洗脱支架术后再狭窄(DES-ISR)患者支架内新生钙化斑块的发生率及预测因素。方法 回顾性连续入组2010年1月—2022年3月于解放军总医院接受光学相干断层成像(OCT)检查的DES-ISR患者。将所有病变按照OCT下是否有新生钙化斑块形成分为新生钙化斑块组和非新生钙化斑块组，收集患者基线资料和手术特征资料，分析两组患者临床资料和病变特征的组间差异，并通过多因素logistic回归分析支架内新生钙化斑块的独立危险因素。结果 纳入包含249个病变的DES-ISR患者230例，平均年龄(63.1±10.4)岁，男性188例(81.7%)，DES-ISR中位发病时间为6(2，9)年，钙化斑块组24例(10.4%)，非钙化斑块组206例(89.6%)。与非钙化斑块组患者相比，钙化斑块组患者男性较多见(100% vs.79.6%，P=0.030)，ISR发生时长较长[8.25(6.00，10.25) vs 5.00(2.00，9.00)，P=0.006]，且病灶分布特征多为弥漫性(61.5% vs 36.3%，P=0.041)。另外，OCT下病变长度更长(31.3 vs 22.3，P=0.003)，并且薄纤维帽粥样硬化斑块(TCFA)的发生率高(73.1% vs 27.8%，P < 0.001)。多因素二元logistic回归分析显示，较高的空腹血糖(OR=1.14，P=0.007)、较长的ISR发生时长(OR=1.17，P=0.001)、更长的病变长度(OR=1.05，P=0.009)、未使用他汀类药物(OR=3.46，P=0.024)是DES-ISR患者支架内新生钙化斑块发生的独立危险因素。结论 DES-ISR患者支架内新生钙化斑块的发生率为10.4%。另外，未使用他汀类药物、较高的空腹血糖、较长的ISR发生时长和更长的病变长度是DES-ISR患者支架内新生钙化斑块形成的独立危险因素。Abstract: Objective To investigate the incidence and predictive factors of calcified plaque in stent in patients with restenosis after drug-eluting stents.Methods The consecutive patients with DES-ISR undergoing optical coherence tomography(OCT) examination in the PLA General Hospital from January 2010 to March 2022 were enrolled retrospectively. All lesions were divided into calcified and non-calcified plaque group according to whether there was calcified plaque formation under OCT. The clinical indicators, intervention-and OCT-related data were collected, the differences between the two groups in clinical data and lesion characteristics were analyzed, and the independent risk factors of calcified plaque in the stent were analyzed by multivariable binary logistic regression.Results 230 DES-ISR patients with 249 lesions were included. Compared with the non-calcified plaque group, the calcified plaque group was more common in men(100% vs. 79.6%, P=0.030), the interval after DES implantation was longer[8.25(6.00, 10.25) vs. 5.00(2.00, 9.00), P=0.006], the lesions showed more diffuse(61.5% vs. 36.3%, P=0.041) and longer in length[31.3(21.3, 36.5) vs. 22.3(15.0, 31.4), P=0.003), and the incidence of and the thin fibrous cap atherosclerotic plaque occurred more frequent(73.1% vs. 27.8%, P < 0.001). Multivariable binary logistic regression analysis demonstrated that higher fasting blood glucose(OR=1.14, P=0.007), longer duration of ISR(OR=1.17, P=0.001), longer lesion length(OR=1.05, P=0.009), and no statins(OR=3.46, P=0.024) were independent predictors of calcified plaque in DES-ISR patients.Conclusion In this study, the incidence of calcified plaque in stents in patients with DES-ISR was 10.4%. In addition, no statin using, higher fasting glucose, longer duration of ISR and longer lesion length were independent risk factors for the calcified plaque in DES-ISR patients.
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表 1 两组基本资料及术后服药比较
Table 1. Comparison of basic data and postoperative medication between the two groups
例(%), X±S, M(P25, P75) 项目 总体(230例) 钙化斑块组(24例) 非钙化斑块组(206例) Z/t/χ2 P 年龄/岁 63.1±10.4 65.3±9.9 62.8±10.5 -0.289 0.197 男性 188(81.7) 24(100) 164(79.6) 4.698 0.030 高血压 141(61.3) 17(70.8) 124(60.2) 1.026 0.311 糖尿病 108(47) 14(58.3) 94(45.6) 1.392 0.238 高脂血症 67(29.1) 7(29.2) 60(29.1) < 0.001 0.997 慢性肾功能不全 7(3.0) 2(8.3) 5(2.4) 0.158 慢性心功能不全 23(10.0) 4(16.7) 19(9.2) 0.625 0.429 冠脉旁路移植术 0 0 0 吸烟史 109(47.4) 12(50) 97(47.1) 0.073 0.787 既往用药史 阿司匹林 219(95.2) 22(91.7) 197(95.6) 0.127 0.722 氯吡格雷 157(68.3) 14(58.3) 143(69.4) 1.219 0.270 替格瑞洛 56(24.3) 3(12.5) 53(25.7) 2.042 0.153 他汀类 202(87.8) 18(75.0) 184(89.3) 2.892 0.089 空腹血糖/(mmol/L) 5.8(5.0，8.3) 6.1(4.8，9.7) 5.8(5.0，8.2) -0.582 0.561 低密度脂蛋白/(mmol/L) 1.8(1.4，2.3) 1.7(1.2，2.2) 1.9(1.4，2.3) -1.089 0.276 
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表 2 两组病变特征及定量冠脉造影分析
Table 2. Analysis of pathological characteristics and quantitative coronary angiography in two groups
例(%), M(P25, P75) 项目 总体(249例) 钙化斑块组(26例) 非钙化斑块组(223例) Z/t/χ2 P 靶血管 0.579 前降支 162(65.1) 19(73.1) 143(64.1) 回旋支 34(13.7) 4(15.4) 30(13.5) 右冠脉 51(20.5) 3(11.5) 48(21.5) 其他 2(0.8) 0 2(0.9) 病变特征 3.516 0.172 体部 144(57.8) 12(46.2) 132(59.2) 开口 16(6.4) 4(15.4) 12(5.4) 分叉 89(35.7) 10(38.5) 79(35.4) ISR发生时长/年 6.00(2.00，9.00) 8.25(6.00，10.25) 5.00(2.00，9.00) -2.759 0.006 ISR的mehran分型 3.045 0.385 Ⅰ 88(35.3) 13(50.0) 75(33.6) Ⅱ 72(28.9) 5(19.2) 67(30.0) Ⅲ 73(29.3) 7(26.9) 66(29.6) Ⅳ 16(6.4) 1(3.8) 15(6.7) 手术前 病变长度QCA/mm 11.3(7.9，15.4) 9.2(7.3，14.0) 11.7(8.0，15.5) -1.321 0.187 参考直径QCA/mm 2.7(2.3，3.1) 2.8(2.2，3.1) 2.7(2.3，3.1) -0.278 0.781 最小管腔直径QCA/mm 1.0(0.7，1.3) 1.2(0.8，1.6) 1.0(0.7，1.3) -1.597 0.110 直径狭窄率QCA/% 62.0(50.7，74.1) 54.9(47.2，69.3) 62.4(50.9，74.7) -1.607 0.108
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表 3 两组OCT定量及定性分析
Table 3. Quantitative and qualitative analysis of two groups of OCT
例(%), M(P25, P75) 项目 总人数
(249例)钙化斑块组
(26例)非钙化斑块组
(223例)Z/t/χ2 P 定量数据 远端参考节段管腔面积OCT/mm2 5.4(4.1，6.7) 5.0(4.3，6.2) 5.4(4.1，6.8) -0.299 0.765 近段参考节段管腔面积OCT/mm2 6.8(5.7，8.2) 6.5(5.8，7.9) 6.9(5.7，8.2) -0.322 0.747 最小管腔面积OCT/mm2 1.9(1.4，2.7) 1.8(1.4，2.7) 1.9(1.4，2.7) -0.492 0.623 最小管腔直径OCT/mm 1.5(1.3，1.8) 1.5(1.3，1.9) 1.5(1.3，1.8) -0.501 0.617 最小支架面积OCT/mm2 6.6(5.4，7.8) 6.8(6.0，8.1) 6.5(5.4，7.8) -0.899 0.369 最小支架直径OCT/mm 2.9(2.6，3.2) 2.9(2.7，3.2) 2.9(2.6，3.2) -0.386 0.700 最小管腔处新生内膜面积OCT/mm2 4.5(3.0，5.5) 4.7(3.2，5.7) 4.5(3.0，5.5) -0.593 0.553 最小管腔处平均新生内膜厚度OCT/mm 0.7(0.5，0.8) 0.7(0.5，0.9) 0.6(0.5，0.8) -0.561 0.575 病变长度/mm 22.8(15.5，32.7) 31.3(21.3，36.5) 22.3(15.0，31，4) -2.951 0.003 面积狭窄百分比/% 67.2(58.5，76.7) 70.5(55.0，78.1) 67.1(58.9，76.5) -0.216 0.829 定性分析 内膜增殖类型 3.081 0.214 异质性 142(57.0) 19(73.1) 123(55.2) 均质性 57(22.9) 4(15.4) 53(23.8) 分层性 50(20.1) 3(11.5) 47(21.1) 病灶分布特征 6.395 0.041 局灶 57(22.9) 3(11.5) 54(24.2) 节段 95(38.2) 7(27.0) 88(39.5) 弥漫 97(39.0) 16(61.5) 81(36.3) 背向散射 0.266 0.606 高 88(35.3) 8(30.8) 80(35.9) 低 161(64.7) 18(69.2) 143(64.1) 斑块破裂 42(16.9) 3(11.5) 39(17.5) 0.240 0.624 支架膨胀不全 7(2.8) 0(0) 7(3.1) >0.999 支架贴壁不良 17(6.8) 1(3.8) 16(7.2) 0.051 0.821 TCFA 81(32.5) 19(73.1) 62(27.8) 21.746 < 0.001 巨噬细胞聚集 94(37.8) 11(42.3) 83(37.2) 0.257 0.613 微通道 67(26.9) 11(42.3) 56(25.1) 3.501 0.061 脂质斑块 187(75.1) 19(73.1) 168(75.3) 0.064 0.801 最大脂质角度/° 300(208，360) 320(184，360) 300(207，360) 0.606 血栓 32(12.9) 4(15.4) 28(12.6) 0.010 0.922
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表 4 Logistic回归分析
Table 4. Logistic regression analysis
自变量 单因素分析 多因素分析 OR(95%CI) P OR(95%CI) P 年龄 1.02(0.98~1.06) 0.432 糖尿病 1.65(0.72~3.75) 0.234 慢性肾功能不全 3.66(0.67~19.75) 0.135 未使用阿司匹林 1.78(0.37~8.58) 0.475 未使用替格瑞洛 2.51(0.73~8.68) 0.146 未使用氯吡格雷 1.40(0.60~3.23) 0.437 未使用他汀类 3.06(1.16~8.02) 0.023 3.46(1.18~10.11) 0.024 空腹血糖 1.10(1.01~1.19) 0.033 1.14(1.04~1.25) 0.007 低密度脂蛋白胆固醇 0.65(0.35~1.23) 0.188 ISR发生时长 1.17(1.07~1.28) 0.001 1.17(1.07~1.29) 0.001 最小管腔直径 1.78(0.89~3.59) 0.105 最小管腔面积 1.12(0.75~1.68) 0.586 最小管腔直径 1.36(0.44~4.13) 0.592 病变长度 1.05(1.02~1.09) 0.005 1.05(1.01~1.10) 0.009 斑块破裂 0.62(0.18~2.15) 0.447 支架贴壁不良 0.52(0.07~4.07) 0.531 巨噬细胞聚集 1.24(0.54~2.82) 0.613
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