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Journal of Peking University (Health Sciences) ›› 2021, Vol. 53 ›› Issue (1): 159-166. doi: 10.19723/j.issn.1671-167X.2021.01.024

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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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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

CLC Number: 

  • R542.2

Figure 1

Study flow diagram"

Table 1

Demographics and baseline characteristics of patients with COVID-19"

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

Table 2

Comparison of cytokines, hs-CRP and ferritin"

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

Figure 2

Distribution and association of cTnI with inflammatory indexes Analyzed by Spearman correlation test, we show that levels of circulatory cardiac troponin I (cTnI) are in positive correlation (ρ>0, P<0.01) with levels of high-sensitivity C-reactive protein (hs-CRP, n=114), ferritin (n=113), receptor of interleukin-2 (IL-2R, n=114), interleukin-6 (IL-6, n=110) and interleukin-8 (IL-8, n=107). The values under level of detection were removed from the correlation test. Abbreviations as in Table 1 and 2."

Table 3

Logistic regression analysis of factors of myocardial injury"

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

Figure 3

The ROC curve of predicting acute myocardial injury of COVID-19 patients Area under ROC of SpO2 is 0.721 (95%CI: 0.561-0.882, P =0.003), and area under ROC of IL-6 is 0.746 (95%CI: 0.636-0.855, P=0.001). Taking both of the two factors into consideration promotes predictive value for myocardial injury of COVID-19 patients. Abbreviations as in Table 1 and 2."

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