不同剂量阿托伐他汀钙对颈动脉斑块内新生血管分级的影响及与炎性反应的相关性

Effects of atorvastatin calcium at varying doses on the neovascularization grade in carotid plaques and its correlation with inflammatory response

目的应用超微血流成像技术(SMI)评估不同剂量阿托伐他汀钙对颈动脉斑块内新生血管分级的影响及其与机体炎症水平的相关性。方法选取2017年1月至2019年12月行超声检查发现有颈动脉斑块的患者,运用SMI检测有新生血管患者240例,按单双号分为阿托伐他汀钙(AT)20 mg/d组(低剂量组)和40 mg/d组(高剂量组),每组120例,治疗3个月。分别于治疗前及治疗3个月后晨起采外周血,分析血常规指标、炎性因子水平以及斑块内新生血管分级变化情况。结果研究过程中2组患者均未出现终点事件及严重不良反应。治疗3个月后,2组患者斑块内新生血管分级均显著下降,且高剂量组治疗效果优于低剂量组(P<0.01)。低剂量AT治疗前后LDL-C与HDL-C水平有显著变化(P<0.05);高剂量AT治疗前后单核细胞(MONO)、ApoE、LDL-C、HDL-C水平的差异有统计学意义(P<0.05),而2组患者治疗前后MHR均呈极显著差异(P<0.01),且高剂量组的MHR值极显著低于低剂量组(P<0.01)。斑块内新生血管分级与MHR值呈正相关,且高剂量AT治疗后,MHR水平在0级与Ⅰ级、Ⅱ级与Ⅲ级新生血管患者间具显著性差异(P<0.05)。进一步流式分析结果显示,高剂量AT可以有效抑制患者外周血中MONO的增殖(P<0.05)。此外,所有患者血清中炎性因子hs-CRP、IL-1β、IL-6、TNF-α的水平较治疗前均有明显改善(P<0.05),且高剂量组的血清炎性因子水平显著低于低剂量组(P<0.05)。结论阿托伐他汀钙有助于改善颈动脉斑块内新生血管分级、机体炎症水平,40 mg/d剂量临床效果更为明显。

Objective To analyze the effects of atorvastatin calcium at varying doses on the neovascularization grading in carotid plaques and its correlation with the inflammatory level by the superb microvascular imaging(SMI).Methods A total of 240 patients with carotid plaques detected by ultrasound who had neovascularization examined by SMI from January 2017 to December 2019 were included.They were assigned into atorvastatin calcium(AT)20mg/d group(n=120)and AT 40mg/d group(n=120)according to the odd-even case number.AT treatment lasted for 3 months.Peripheral blood was collected in the morning before and after 3 months of treatment.Changes in peripheral blood routine indicators,inflammatory factors and neovascularization grading in carotid plaques were analyzed in the two groups before and after treatment.Results End-points or serious adverse events were not reported in both groups during the study period.After 3 months of treatment,the neovascularization grade in carotid plaques was significantly reduced in both groups,which was significantly pronounced in the AT 40mg/d group than the AT 20mg/d group(P<0.01).There were significantly changes in the low-density lipoprotein-cholesterol(LDL-C)and high-density lipoprotein-cholesterol(HDL-C)levels before and after low-dose AT treatment(P<0.05),and there were significant differences in the monocyte cell count(MONO),apolipoprotein E(ApoE),LDL-C and HDL-C levels before and after high-dose AT treatment(P<0.05).An extremely significant difference in the monocytes-to-HDL-C ratio(MHR)was detected in both groups before and after treatment(P<0.01),and the MHR threshold was significantly lower in the AT 40mg/d group than the AT 20mg/d group(P<0.01).The neovascularization grade in carotid plaques was positively correlated with MHR.MHR level was significantly different between grade 0 versusⅠ,and between gradeⅡversusⅢneovascularization after high-dose AT treatment(P<0.05).Further flow cytometry data showed that high-dose AT treatment could effectively inhibit the proliferation of MONO in the peripheral blood of patients with carotid plaques(P<0.05).In addition,serum inflammatory factors,such as high-sensitivity C-reactive protein(hs-CRP),interleukin(IL)-1β,IL-6 and tumour necrosis factor alpha(TNF-α)in all patients were significantly reduced than those before treatment(P<0.05),which were significantly lower in the AT 40mg/d group than the AT 20mg/d group(P<0.05).Conclusion AT improves the neovascularization grade in carotid plaques and reduces inflammation in the body,and the clinical effect of 40mg/d AT is much more obvious.