Effect of PCSK9 inhibitor on microcirculation function and left ventricular remodeling after PCI in acute ST-segment elevation myocardial infarction
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摘要: 目的 探究PCSK9抑制剂对急性ST段抬高型心肌梗死(STEMI)经皮冠状动脉介入(PCI)术后的微循环功能及左心室重构的影响。方法 采用前瞻性单中心随机对照试验方法，选取2019年12月—2020年12月郑州大学第二附属医院收治的90例行PCI治疗的急性STEMI患者，按随机数字对照表法分为对照组和PCSK9抑制剂组(PCSK9i组)各45例。两组患者PCI术后均行阿司匹林、氯吡格雷、控制其他相关危险因素等常规治疗。对照组予阿托伐他汀治疗，PCSK9i组在对照组基础上加用PCSK9抑制剂治疗，两组均治疗6个月。观察2组治疗前后的冠状动脉(冠脉)微循环功能指标：冠脉血流储备(CFR)、微循环阻力指数(IMR)；术前术后及复查造影时的冠脉血流分级；左心室重构指标：左室收缩末期内径(LVESD)、左室舒张末期内径(LVEDD)、左室射血分数(LVEF)。结果 对照组和PCSK9i组各有40例患者完成研究，治疗6个月后，两组的LVESD、LVEDD水平均低于治疗前(P< 0.05)，CFR、IMR、LVEF水平高于治疗前(P< 0.05)。PCSK9i组的IMR水平低于对照组(P< 0.05)，CFR、LVEF水平高于对照组(P< 0.05)，冠脉血流3级者高于对照组(P< 0.05)。结论 PCSK9抑制剂可改善心肌梗死后冠脉微循环及左心室重构。Abstract: Objective To explore the effect of PCSK9 inhibitor on the microcirculation function and left ventricular remodeling after PCI in acute ST-segment elevation myocardial infarction.Methods A prospective, single-center, randomized, controlled trial method was used to select 90 patients with acute ST-segment elevation myocardial infarction treated by PCI who were admitted to the Second Affiliated Hospital of Zhengzhou University from December 2019 to December 2020. Randomized The digital control table method was divided into 45 cases in the Control group and the PCSK9i group(PCSK9 inhibitor group). Both groups of patients received conventional treatments such as aspirin, clopidogrel, and control of other related risk factors after PCI. The Control group was treated with atorvastatin, and the PCSK9i group was treated with PCSK9 inhibitors on the basis of the Control group. Both groups were treated for 6 months. We observed the coronary microcirculation function indexes before and after treatment: coronary blood flow reserve(CFR), microcirculation resistance index(IMR); coronary blood flow grading before and after surgery and during reexamination, left ventricular remodeling indexes: left ventricular end systolic diameter(LVESD), left ventricular end diastolic diameter(LVEDD), left ventricular ejection fraction(LVEF).Results There were 40 patients in the Control group and PCSK9i group each. After 6 months of treatment, the levels of LVESD, LVEDD in the two groups lower than before treatment(P< 0.05), CFR, IMR, LVEF levels were higher than before treatment(P< 0.05). The levels of IMR in the PCSK9i group were lower than in the Control group(P< 0.05), and the levels of CFR and LVEF were higher than in the Control group(P< 0.05). The coronary blood flow in the PCSK9i group was higher than that in the Control group(P< 0.05).Conclusion PCSK9 inhibitor can improve vascular endothelial function, and improve left ventricular remodeling after myocardial infarction.
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Key words:
- PCSK9 inhibitor /
- PCI /
- microcirculation disorder /
- left ventricular remodeling
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表 1 两组患者基线比较
Table 1. General data
X±S 项目 对照组(40例) PCSK9i组(40例) χ2/t P 男/例(%) 27(67.5) 29(72.5) 0.238 0.626 年龄/岁 63.33±10.46 59.72±11.71 1.440 0.449 收缩压/mmHg 127.2±19.08 134.5±17.09 1.802 0.075 舒张压/mmHg 78.48±12.06 82.35±11.01 1.501 0.137 高血压史/例(%) 11(27.5) 13(32.5) 0.238 0.626 糖尿病史/例(%) 4(10.0) 8(20.0) 0.882 0.348 多支病变/例(%) 26(65.0) 23(57.5) 0.474 0.491 梗死部位/例(%) 前壁 21(52.5) 19(47.5) 0.200 0.655 高侧壁 8(20.0) 9(22.5) 0.075 0.785 下后壁 11(27.5) 12(30) 0.061 0.805 罪犯血管/例(%) 左主干 2(5.0) 2(5.0) - 1 左前降支 13(32.5) 11(27.5) 0.238 0.626 左回旋支 7(17.5) 9(22.5) 0.313 0.576 右冠 12(30.0) 11(27.5) 0.061 0.805 对角支/钝缘支 6(15.0) 7(17.5) 0.251 0.617 支架数量/枚 1.7±0.69 1.9±0.778 -1.142 0.253 药物球囊数量/枚 1.65±0.533 1.55±0.597 0.79 0.432 病变狭窄程度/例(%) 70%~90% 13(32.5) 12(30.0) 0.058 0.809 91%~99% 27(67.5) 28(70.0) 0.058 0.809 实验室检查 NT-proBNP/(ng·mL-1) 2089.28±1536.7 2106.88±1544.33 -0.231 0.817 cTnI/(μg·L-1) 15.43±8.81 15±8.99 -0.197 0.844 血运重建后药物/例(%) 阿司匹林 39(97.5) 38(95.0) - 1 氯吡格雷 20(50.0) 19(47.5) 0.050 0.823 替格瑞洛 20(50.0) 21(52.5) 0.050 0.823 β受体阻滞剂 38(95.0) 37(92.5) - 1 ACEI/ARB 22(55.0) 21(52.5) 0.050 0.823 院前用药/例(%) 氨氯地平 10(25.0) 11(27.5) 0.065 0.799 二甲双胍 3(7.5) 6(15.0) - 0.481 注：NT-proBNP：N末端B型钠尿肽原；cTnI：心肌肌钙蛋白I。 
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表 2 两组患者治疗前后血脂指标水平比较
Table 2. Blood lipid index levels before and after treatment
mmol/L, X±S 组别 TG TC 治疗前 治疗后 t值 P值 治疗前 治疗后 t值 P值 对照组(40例) 2.96±1.16 2.13±1.26 3.194 0.003 4.58±1.10 3.98±0.93 3.086 0.04 PCSK9i组(40例) 2.79±1.1 1.41±0.61 6.778 < 0.01 4.4±1.01 3.53±1.06 4.173 < 0.01 t值 -0.717 -3.104 -0.394 -2.097 P值 0.476 0.003 0.695 0.039 组别 HDL-C LDL-C 治疗前 治疗后 t值 P值 治疗前 治疗后 t值 P值 对照组(40例) 1.16±0.25 1.29±0.27 -2.074 0.045 2.6±0.98 1.79±0.27 4.841 < 0.01 PCSK9i组(40例) 1.11±0.3 1.35±0.29 -3.478 0.01 2.67±1.13 0.95±0.36 8.553 < 0.01 t值 -0.778 0.978 0.305 -11.58 P值 0.439 0.331 0.761 < 0.01
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表 3 两组治疗前后血管内皮功能指标水平比较
Table 3. Index levels of vascular endothelial function before and after treatment
X±S 组别 EF-1/(ng·L-1) NO/(μmol·L-1) 治疗前 治疗后 t值 P值 治疗前 治疗后 t值 P值 对照组(40例) 91.80±10.35 70.27±5.99 10.738 < 0.01 55.89±8.64 70.98±9.88 -6.924 < 0.01 PCSK9i组(40例) 91.79±9.94 53.5±6 20.273 < 0.01 56.4±8.69 79.74±10 -10.359 < 0.01 t值 -0.161 -12.314 0.178 4.057 P值 0.872 < 0.01 0.86 < 0.01
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表 4 两组患者治疗前后炎症因子指标水平比较
Table 4. Inflammatory factors before and after treatment
X±S 组别 CRP/(mg·L-1) TNF-α/(pg·mL-1) IL-6/(ng·mL-1) 治疗前 治疗后 t值 P值 治疗前 治疗后 t值 P值 治疗前 治疗后 t值 P值 对照组(40例) 11.75±3.24 7.69±2.61 6.930 < 0.01 126.01±23.7 57.79±14.43 14.358 < 0.01 59.24±14.28 28.55±8.92 12.658 < 0.01 PCSK9i组(40例) 12.27±3.35 5.18±1.92 12.844 < 0.01 127.98±22.39 36.43±9.41 22.277 < 0.01 59.34±134 17.4±6.68 17.732 < 0.01 t值 0.601 -4.897 0.516 -7.882 -0.175 -6.355 P值 0.550 < 0.01 0.608 < 0.01 0.862 < 0.01
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表 5 两组治疗前后微循环功能指标水平比较
Table 5. Microcirculation function indexes before and after treatment
X±S 组别 CFR IMR 治疗前 治疗后 t值 P值 治疗前 治疗后 t值 P值 对照组(40例) 1.34±0.36 1.71±0.39 -4.654 < 0.01 22.38±3.06 28.26±2.78 -9.229 < 0.01 PCSK9i组(40例) 1.35±0.36 2.06±0.54 -6.958 < 0.01 22.63±3.22 25.5±2.59 -4.261 < 0.01 t值 0.242 3.218 0.294 -4.846 P值 0.810 0.020 0.769 < 0.01
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表 6 两组治疗前后的冠脉血流分级比较
Table 6. Coronary blood flow classification before and after treatment
例 组别 术前 术后即刻 术后6个月 0级 1级 2级 3级 0级 1级 2级 3级 0级 1级 2级 3级 对照组(40例) 25 15 0 0 0 0 9 31 2 4 8 26 PCSK9i组(40例) 26 13 1 0 0 0 8 32 0 1 5 34 统计值 -0.144 -0.272 -2.185 P值 0.886 0.786 0.029 注：0级：血管远端无造影剂填充；1级：造影剂在狭窄处部分显影；2级：造影剂能填充血管但显影速度较慢；3级造影剂能快速、完全充盈血管。
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表 7 两组治疗前后左心室重构指标水平比较
Table 7. Left ventricular remodeling indexes before and after treatment
X±S 组别 LVEF/% LVEDD/mm LVESD/mm 治疗前 治疗后 t值 P值 治疗前 治疗后 t值 P值 治疗前 治疗后 t值 P值 对照组(40例) 48.52±6.28 53.48±6.67 -3.063 0.04 53.73±3.95 50.2±4.5 3.827 < 0.01 41.28±3.74 36.96±3.19 5.128 < 0.01 PCSK9i组(40例) 47.98±6.08 56.23±5.61 -5.68 < 0.01 54.57±3.67 46.7±4.87 10.05 < 0.01 41.89±3.98 34.88±2.69 7.805 < 0.01 t值 -0.633 2.023 1.107 -3.233 0.433 -3.267 P值 0.528 0.047 0.272 0.002 0.666 0.002
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