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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 ,
  • 张瑞涛 ,
  • 郭丽君 ,
  • 肖晗 ,
  • 祖凌云 ,
  • 张幼怡 ,
  • 程秦 ,
  • 赵志伶 ,
  • 葛庆岗 ,
  • 高炜
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  • 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

  网络出版日期: 2021-02-07

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

  • Lin-cheng YANG ,
  • Rui-tao ZHANG ,
  • Li-jun GUO ,
  • Han XIAO ,
  • Ling-yun ZU ,
  • You-yi ZHANG ,
  • Qin CHENG ,
  • Zhi-ling ZHAO ,
  • Qing-gang GE ,
  • Wei GAO
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  • 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 date: 2020-08-14

  Online published: 2021-02-07

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。

本文引用格式

杨林承 , 张瑞涛 , 郭丽君 , 肖晗 , 祖凌云 , 张幼怡 , 程秦 , 赵志伶 , 葛庆岗 , 高炜 . 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[J]. 北京大学学报(医学版), 2021 , 53(1) : 159 -166 . DOI: 10.19723/j.issn.1671-167X.2021.01.024

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.

参考文献

[1] Xu X, Chen P, Wang J, et al. Evolution of the novel coronavirus from the ongoing Wuhan outbreak and modeling of its spike protein for risk of human transmission[J]. Sci China Life Sci, 2020,63(3):457-460.
[2] Lu R, Zhao X, Li J, et al. Genomic characterisation and epide-miology of 2019 novel coronavirus: Implications for virus origins and receptor binding[J]. Lancet, 2020,395(10224):565-574.
[3] Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: A descriptive study[J]. Lancet, 2020,395(10223):507-513.
[4] Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China[J]. Lancet, 2020,395(10223):497-506.
[5] Wang D, Hu B, Hu C, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China[J]. JAMA, 2020,323(11):1061-1069.
[6] 魏之瑶, 钱海燕. 新型冠状病毒肺炎患者的心肌损伤表现[J]. 中华心血管病杂志, 2020,48(6):439-442.
[7] Fourth universal definition of myocardial infarction (2018)[J]. Rev Esp Cardiol (Engl Ed), 2019,72(1):72.
[8] 陈晨, 陈琛, 严江涛, 等. 新型冠状病毒肺炎危重型患者心肌损伤及患有心血管基础疾病的情况分析[J]. 中华心血管病杂志, 2020,48(7):567-571.
[9] Guan WJ, Ni ZY, Hu Y, et al. Clinical characteristics of coronavirus disease 2019 in China[J]. N Engl J Med, 2020,382(18):1708-1720.
[10] Koong AC, Chen EY, Giaccia AJ. Hypoxia causes the activation of nuclear factor kappa B through the phosphorylation of I kappa B alpha on tyrosine residues[J]. Cancer Res, 1994,54(6):1425-1430.
[11] Lum H, Roebuck KA. Oxidant stress and endothelial cell dysfunction[J]. Am J Physiol Cell Physiol, 2001,280(4):C719-C741.
[12] Csiszar A, Wang M, Lakatta EG, et al. Inflammation and endothelial dysfunction during aging: role of NF-kappaB[J]. J Appl Physiol (1985), 2008,105(4):1333-1341.
[13] Iida T, Mine S, Fujimoto H, et al. Hypoxia-inducible factor-1alpha induces cell cycle arrest of endothelial cells[J]. Genes Cells, 2002,7(2):143-149.
[14] Aoki M, Nata T, Morishita R, et al. Endothelial apoptosis induced by oxidative stress through activation of NF-kappaB: antiapoptotic effect of antioxidant agents on endothelial cells[J]. Hypertension, 2001,38(1):48-55.
[15] Chen Y, Liu Y, Dorn GW 2nd. Mitochondrial fusion is essential for organelle function and cardiac homeostasis[J]. Circ Res, 2011,109(12):1327-1331.
[16] Chen Q, Moghaddas S, Hoppel CL, et al. Ischemic defects in the electron transport chain increase the production of reactive oxygen species from isolated rat heart mitochondria[J]. Am J Physiol Cell Physiol, 2008,294(2):C460-C466.
[17] Chiong M, Wang ZV, Pedrozo Z, et al. Cardiomyocyte death: Mechanisms and translational implications[J]. Cell Death Dis, 2011,2(12):e244.
[18] Nunez C, Victor VM, Marti M, et al. Role of endothelial nitric oxide in pulmonary and systemic arteries during hypoxia[J]. Nitric Oxide, 2014,37:17-27.
[19] Yang X, Yu Y, Xu J, et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: A single-centered, retrospective, observational study[J]. Lancet Respir Med, 2020,8(5):475-481.
[20] Hui H, Zhang YQ, Yang X, et al. Clinical and radiographic features of cardiac injury in patients with 2019 novel coronavirus pneumonia[J]. MedRxiv, 2020, 2020.02.24.20027052.
[21] Channappanavar R, Perlman S. Pathogenic human coronavirus infections: Causes and consequences of cytokine storm and immunopathology[J]. Semin Immunopathol, 2017,39(5):529-539.
[22] Neumann FJ, Ott I, Marx N, et al. Effect of human recombinant interleukin-6 and interleukin-8 on monocyte procoagulant activity[J]. Arterioscler Thromb Vasc Biol, 1997,17(12):3399-3405.
[23] Tanaka T, Narazaki M, Kishimoto T. Immunotherapeutic implications of IL-6 blockade for cytokine storm[J]. Immunotherapy, 2016,8(8):959-970.
[24] Ding Y, Wang H, Shen H, et al. The clinical pathology of severe acute respiratory syndrome (SARS): A report from China[J]. J Pathol, 2003,200(3):282-289.
[25] 国家卫生健康委员会. 新型冠状病毒诊疗方案(试行第七版)[EB]. (2020-03-03)[2020-04-15]. http://www.nhc.gov.cn/yzygj/s7653p/202003/46c9294a7dfe4cef80dc7f5912eb1989/files/ce3e6945832a438eaae415350a8ce964.pdf.
[26] Watts ER, Walmsley SR. Inflammation and hypoxia: HIF and PHD isoform selectivity[J]. Trends Mol Med, 2019,25(1):33-46.
[27] Campbell EL, Bruyninckx WJ, Kelly CJ, et al. Transmigrating neutrophils shape the mucosal microenvironment through localized oxygen depletion to influence resolution of inflammation[J]. Immunity, 2014,40(1):66-77.
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