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北京大学学报（医学版） ›› 2021, Vol. 53 ›› Issue (1): 159-166. doi: 10.19723/j.issn.1671-167X.2021.01.024

• 论著 • 上一篇    下一篇

低氧状态及炎症反应是新型冠状病毒肺炎患者发生急性心肌损伤的危险因素

杨林承1,张瑞涛1,郭丽君1,肖晗1,祖凌云1,张幼怡1,程秦2,赵志伶3,葛庆岗3,高炜1,Δ()   

  1. 1.北京大学第三医院心内科,国家卫生健康委员会心血管分子生物学与调节肽重点实验室,分子心血管学教育部重点实验室,心血管受体研究北京市重点实验室,北京 100191
    2.北京大学第三医院呼吸与危重医学科,北京 100191
    3.北京大学第三医院危重医学科,北京 100191
  • 收稿日期:2020-08-14 出版日期:2021-02-18 发布日期:2021-02-07
  • 通讯作者: 高炜 E-mail:weigao@bjmu.edu.cn

Hypoxia and inflammation are risk factors for acute myocardial injury in patients with coronavirus disease 2019

YANG Lin-cheng1,ZHANG Rui-tao1,GUO Li-jun1,XIAO Han1,ZU Ling-yun1,ZHANG You-yi1,CHENG Qin2,ZHAO Zhi-ling3,GE Qing-gang3,GAO Wei1,Δ()   

  1. 1. Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital & NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides & Key Laboratory of Molecular Cardiovascular Science, Ministry of Education & Beijing Key Laboratory of Cardiovascular Receptors Research, Beijing 100191, China
    2. Department of Respiratory and Critical Care Medicine, Peking University Third Hospital, Beijing 100191, China
    3. Department of Intensive Care Medicine, Peking University Third Hospital, Beijing 100191, China
  • Received:2020-08-14 Online:2021-02-18 Published:2021-02-07
  • Contact: Wei GAO E-mail:weigao@bjmu.edu.cn

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摘要：

目的: 寻找新型冠状病毒肺炎(coronavirus disease 2019,COVID-19)患者发生急性心肌损伤的危险因素。方法: 本研究为单中心COVID-19住院患者的回顾性队列研究,共纳入149例COVID-19确诊患者,依据2018年欧洲心脏病学会年会发布的第四版心肌梗死全球统一定义中关于心肌损伤的诊断标准,将患者分为心肌损伤组(19例)及非心肌损伤组(130例)。收集全部入组患者的临床信息及实验室化验结果,并分析COVID-19患者发生急性心肌损伤的危险因素。结果: 与非心肌损伤组患者相比,心肌损伤组患者年龄更大,危重症患者比例更高(P<0.05),入院时呼吸频率更快,未吸氧状态外周血氧饱和度(percutaneous oxygen saturation,SpO2)偏低(P<0.05)。心肌损伤组患者除肿瘤坏死因子α(tumor necrosis factor α,TNF-α)外,其余炎症因子水平均高于非心肌损伤组(P<0.05)。多因素Logistic回归分析发现,入院时未吸氧状态SpO2水平偏低(OR=0.860,95%CI:0.779~0.949,P=0.003)及血白细胞介素-6(interleukin-6,IL-6)水平升高(OR=1.068,95%CI:1.019~1.120,P=0.006)为COVID-19患者发生急性心肌损伤的独立危险因素。结论: 低氧状态及炎症在COVID-19患者发生急性心肌损伤的病理生理过程中起到了重要作用。

关键词: β冠状病毒, 急性心肌损伤, 白细胞介素-6, 炎症

Abstract:

Objective: To investigate the risk factors for acute myocardial injury in coronavirus disease 2019 (COVID-19) patients.Methods: This is a retrospective analysis of a COVID-19 cohort, in which 149 confirmed COVID-19 patients enrolled were divided into the group of myocardial injury (19 cases) and the group of non-myocardial injury (130 cases). Myocardial injury was defined according to Fourth universal definition of myocardial infarction released by European Society of Cardiology (ESC) in 2018, that cardiac troponin (cTn) was above 99th percentile of the reference level. Clinical information and results of laboratory tests of the eligible patients were collected. Factors associated with myocardial injury in COVID-19 patients were evaluated.Results: Compared with the group of non-injury, the patients in the group of injury were older and had a larger proportion of severe or critical cases (P<0.05), higher respiratory rate and lower percutaneous oxygen saturation (SpO2) without oxygen therapy on admission (P<0.05). All inflammatory indexes except for tumor necrosis factor α (TNF-α) showed significant elevation in the patients of the group of injury (P<0.05). Analyzed by Spearman correlation test, we showed that the levels of circulatory cTnI were in positive correlation with the levels of high-sensitivity C-reactive protein (hs-CRP), ferritin, receptor of interleukin-2 (IL-2R), interleukin-6 (IL-6) and interleukin-8 (IL-8) (ρ>0, P<0.05). Lower SpO2 without oxygen therapy on admission (OR: 0.860, 95%CI: 0.779-0.949, P=0.003) and higher plasma IL-6 levels (OR: 1.068, 95%CI: 1.019-1.120, P=0.006) were independent risk factors for acute myocardial injury in the patients with COVID-19 by multivariate Logistic regression analyses.Conclusion: Hypoxic state and inflammation may play a key role in the pathogenesis of acute myocardial injury in COVID-19 patients.

Key words: Betacoronavirus, Acute myocardial injury, Interleukin-6, Inflammation

中图分类号: 

  • R542.2

图1

研究流程图"

表1

COVID-19确诊患者基础资料及组间比较"

Items Myocardial injury (n=19) Non-myocardial injury (n=130) t/Z/χ2value P value
General information
Age/years, M (P25, P75) 68.0 (62.0, 77.0) 61.5 (50.0, 69.0) -2.377 0.017
Female, n(%) 10 (52.6) 66 (50.8) 0.023 1.000
Severe or critically severe cases, n(%) 18 (94.7) 72 (55.4) 10.733 0.001
Previous medical history, n(%)
Hypertension 13 (68.4) 44 (33.8) 8.390 0.005
Diabetes 4 (21.1) 15 (16.2) 0.285 0.528
Hyperlipidemia 2 (10.5) 4 (3.1) 2.380 0.169
Smoking history 4 (21.1) 13 (10.0) 2.004 0.236
Cerebrovascular disease 2 (10.5) 5 (3.8) 1.652 0.219
Vital signs on admission
Heart rate/(beat/min), x-±s 93.7±18.9 91.1±17.0 -0.626 0.532
Systolic pressure/mmHg, x-±s 131.8±26.5 132.4±19.2 0.092 0.928
Diastolic pressure/mmHg, x-±s 80.2±16.3 80.6±14.5 0.097 0.924
Respiratory rate/(time/min), M (P25, P75) 30.0 (21.0, 36.0) 21.0 (20.0, 24.0) -3.981 <0.001
SpO2/%, M (P25, P75) 92.0 (79.0, 96.5) 97.0 (94.0, 98.0) -2.978 0.003
Blood routine, M (P25, P75)
White blood cell/(×109/L) 10.10 (5.14, 13.4) 5.38 (4.39, 6.70) -3.062 0.002
Neutrophil/(×109/L) 7.88 (4.30, 12.58) 3.77 (2.66, 5.07) -3.588 <0.001
Lymphocyte/(×109/L) 0.58 (0.40, 1.01) 1.01 (0.69, 1.46) -3.700 <0.001
Scr/(μmol/L), x-±s 87.0±29.1 70.5±20.8 -2.811 0.006
Biomarkers of myocardial injury, M (P25, P75)
CK-MB/(μg/L) 2.90 (1.90, 6.30) 0.70(0.40,1.20) -4.843 <0.001
cTnI/(ng/L) 73.6 (49.5, 229.5) 4.6 (3.1, 8.7) -6.764 <0.001
NT-proBNP/(μg/L), M (P25, P75) 1 062.0 (373.0, 1 847.0) 121.0 (63.0, 248.0) -5.259 <0.001
D-dimer*/(mg/L), M (P25, P75) 2.56 (1.62, 5.56) 0.85 (0.48, 1.54) -3.966 <0.001
Treatment, n(%)
Glucocorticoid 9 (47.4) 26 (20.0) 6.909 0.009
Mechanical ventilation 9 (47.4) 5 (3.8) 36.885 <0.001
In-hospital death, n(%) 8 (42.1) 7 (5.4) 24.689 <0.001

表2

组间hs-CRP、铁蛋白及细胞因子浓度比较"

Items Myocardial injury (n=19) Non-myocardial injury (n=130) Z value P value
hs-CRP/(mg/L) 89.40 (51.30, 139.80) 26.80 (4.95, 71.00) -3.500 <0.001
Ferritin/(μg/L) 1 097.90 (727.73, 2 106.40) 630.50 (358.75, 1 265.80) -2.671 0.008
IL-2R/(U/mL) 1 180.00 (642.00, 1 538.00) 658.00 (443.75, 973.25) -2.942 0.003
IL-6/(ng/L) 50.79 (19.62, 143.20) 19.51 (5.80, 44.98) -3.435 0.001
IL-8/(ng/L) 24.30 (12.80, 43.20) 13.70 (8.23, 24.15) -2.642 0.008
TNF-α/(ng/L) 10.30 (8.90, 13.70) 8.70 (6.30, 11.80) -1.684 0.092

图2

血cTnI水平与各炎症标志物水平间的相关性及其分布情况"

表3

与COVID-19患者发生急性心肌损伤相关因素的Logistic回归分析"

Factors Univariate analysis Multivariate analysis (Enter) Multivariate analysis
(backward LR, last step)
OR (95%CI) P OR (95%CI) P value OR (95%CI) P value
Age (1-year-old) 1.060 (1.017-1.104) 0.006 1.071 (0.989-1.161) 0.093 1.085 (1.006-1.169) 0.034
Respiratory rate (1 per minute) 1.134 (1.047-1.229) 0.002 1.028 (0.963-1.096) 0.408
SpO2 0.859 (0.794-0.929) <0.001 0.874 (0.780-0.979) 0.020 0.860 (0.779-0.949) 0.003
Hypertension (No vs. Yes) 0.236 (0.084-0.664) 0.006 0.263 (0.047-1.458) 0.126 0.220 (0.044-1.097) 0.065
SCr (1 μmol/L) 1.026 (1.006-1.046) 0.011 1.010 (0.981-1.040) 0.507
hs-CRP (10 mg/L) 1.131 (1.053-1.216) 0.001 0.999 (0.871-1.145) 0.984
Ferritin (100 μg/L) 1.056 (1.015-1.098) 0.007 1.015 (0.947-1.088) 0.673
IL-2R (10 U/mL) 1.011 (1.003-1.018) 0.005 1.002 (0.988-1.016) 0.791
IL-6 (10 ng/L) 1.055 (1.008-1.015) 0.020 1.056 (1.005-1.111) 0.031 1.068 (1.019-1.120) 0.006
IL-8 (10 ng/L) 1.203 (1.033-1.401) 0.017 1.043 (0.836-1.302) 0.708

图3

预测COVID-19患者急性心肌损伤的ROC曲线"

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CN 11-4691/R
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