合并高血压、冠心病、糖尿病的新型冠状病毒肺炎患者发生病死的危险因素分析

doi:10.19723/j.issn.1671-167X.2020.03.004

摘要/Abstract

摘要：

目的新型冠状病毒肺炎(corona virus disease 2019,COVID-19)相关心肌损伤的发病机制尚不清楚,对结局的影响证据尚不充分,本研究旨在探讨合并高血压、冠心病、糖尿病的COVID-19患者发生病死的可能危险因素。方法本研究为单中心回顾性研究,分析了北京大学援鄂国家医疗队于2020年1月29日至2020年3月10日在武汉华中科技大学同济医学院附属同济医院中法新城院区收治的COVID-19患者。鼻咽拭子标本检测COVID-19病毒核酸阳性以及合并高血压和/或糖尿病和/或冠心病为纳入标准,收集符合条件的患者的临床资料和实验室检查结果,评估COVID-19患者发生病死的相关因素。结果共有94例患者纳入本研究中,其中存活患者81例,病死患者13例,平均年龄 66.7 岁。入院生命体征:与存活组患者相比,病死组患者基础心率较快(103.2次/min vs. 88.4次/min, P=0.004), 呼吸急促(29.0次/min vs. 20.0次/min, P<0.001)。血常规提示:病死组患者中性粒细胞计数较高(9.2×10⁹/L vs. 3.8×10⁹/L, P<0.001), 淋巴细胞计数较低(0.5×10⁹/L vs. 1.1×10⁹/L, P<0.001)。心肌损伤标记物提示:病死组患者肌酸激酶同工酶MB(creatine kinase MB,CK-MB;3.2 μg/L vs. 0.8 μg/L, P<0.001)、高敏肌钙蛋白Ⅰ (high sensitivity cardiac troponinⅠ,hs-cTNⅠ; 217.2 ng/L vs. 4.9 ng/L, P<0.001)、N末端B型利钠肽原(N-terminal pro brain natriuretic peptide,NT-proBNP; 945.0 μg/L vs. 154.0 μg/L, P <0.001)较高。炎症因子提示:病死组患者铁蛋白(770.2 μg/L vs. 622.8 μg/L, P =0.050)、白细胞介素-2受体(interleukin-2 recepter,IL-2R;1 586.0 U/mL vs. 694.0 U/mL, P <0.001)、白细胞介素-6(interleukin-6,IL-6; 82.3 ng/L vs. 13.0 ng/L, P <0.001)、白细胞介素-10(interleukin-10,IL-10; 9.8 ng/L vs. 5.0 ng/L, P <0.001)较高。单因素Logistic回归分析发现:高龄、不吸氧血氧饱和度低、淋巴细胞计数低、发生心肌损伤、IL-2R、IL-6、IL-10指标异常升高是COVID-19患者合并高血压、冠心病、糖尿病病死的相关因素。多因素Logistic回归分析发现:高龄(OR=1.11, 95%CI =1.03~1.19, P =0.026)、不吸氧血氧饱和度低(OR=0.85, 95% CI =0.72~0.99, P =0.041)、IL-10异常(>9.1 ng/L;OR=101.93, 95%CI =4.74~2190.71, P =0.003)是COVID-19患者合并高血压、冠心病、糖尿病病死的独立危险因素。结论高龄、不吸氧血氧饱和度低、淋巴细胞计数低、发生心肌损伤、IL-2R、IL-6、IL-10指标异常升高是COVID-19患者合并高血压、冠心病、糖尿病病死的相关因素;高龄、不吸氧血氧饱和度低、IL-10异常(>9.1 ng/L)是COVID-19患者合并高血压、冠心病、糖尿病病死的独立危险因素。

关键词: 新型冠状病毒肺炎, 高血压, 糖尿病, 冠心病, 危险因素

Abstract:

Objective: The pathogenesis of myocardial injury upon corona virus disease 2019 (COVID-19) infection remain unknown,evidence of impact on outcome is insufficient, therefore, we aim to investigate the risk factors for death among COVID-19 patients combined with hypertension, coronary heart disease or diabetes in this study.Methods: This was a single-centered, retrospective, observational study. Patients of Sino-French Eco-City section of Tongji Hospital, Wuhan, China attended by Peking University Supporting Medical Team and admitted from Jan. 29, 2020 to Mar. 20, 2020 were included. The positive nucleic acid of COVID-19 virus and combination with hypertension, coronary heart disease or diabetes were in the standard. We collected the clinical data and laboratory examination results of the eligible patients to evaluate the related factors of death.Results: In the study, 94 COVID-19 patients enrolled were divided into the group of death (13 cases) and the group of survivors (81 cases), the average age was 66.7 years. Compared with the survival group, the death group had faster basal heart rate(103.2 beats/min vs. 88.4 beats /min, P=0.004), shortness of breath(29.0 beats /min vs. 20.0 beats /min, P<0.001), higher neutrophil count(9.2×10⁹/L vs. 3.8×10⁹/L, P<0.001), lower lymphocyte count(0.5×10⁹/L vs. 1.1×10⁹/L, P<0.001), creatine kinase MB(CK-MB, 3.2 μg/L vs. 0.8 μg/L, P<0.001), high sensitivity cardiac troponin Ⅰ(hs-cTnⅠ, 217.2 ng/L vs. 4.9 ng/L, P<0.001), N-terminal pro brain natriuretic peptide(NT-proBNP; 945.0 μg/L vs. 154.0 μg/L, P<0.001), inflammatory factor ferritin(770.2 μg/L vs. 622.8 μg/L , P=0.050), interleukin-2 recepter(IL-2R, 1 586.0 U/mL vs. 694.0 U/mL, P<0.001), interleukin-6(IL-6, 82.3 ng/L vs. 13.0 ng/L, P<0.001), interleukin-10(IL-10, 9.8 ng/L vs. 5.0 ng/L, P<0.001)were higher than those in the survival group. Univariate logistic regression analysis showed that the risk factors for death were old age, low non oxygen saturation, low lymphocyte count, myocardial injury, abnormal increase of IL 2R, IL-6, and IL-10. Multivariate regression showed that old age (OR=1.11, 95%CI=1.03-1.19, P=0.026), low non oxygen saturation(OR=0.85, 95%CI=0.72-0.99, P=0.041), and abnormal increase of IL-10(>9.1 ng/L, OR=101.93, 95%CI=4.74-2190.71, P=0.003)were independent risk factors for COVID-19 patients combined with hypertension, coronary heart disease or diabetes.Conclusion: In COVID-19 patients combined with hypertension, coronary heart disease or diabetes, the risk factors for death were old age, low non oxygen saturation, low lymphocyte count, myocardial injury, and abnormal increase of IL-2R, IL-6, and IL-10. Old age, low non oxygen saturation and abnormal increase of IL-10 were independent risk factors.

Key words: COVID-19, Hypertension, Coronary heart disease, Diabetes, Risk factors

中图分类号:

R563.1

杨航,杨林承,张瑞涛,凌云鹏,葛庆岗. 合并高血压、冠心病、糖尿病的新型冠状病毒肺炎患者发生病死的危险因素分析[J]. 北京大学学报（医学版）, 2020, 52(3): 420-424.

Hang YANG,Lin-cheng YANG,Rui-tao ZHANG,Yun-peng LING,Qing-gang GE. Risks factors for death among COVID-19 patients combined with hypertension, coronary heart disease or diabetes[J]. Journal of Peking University (Health Sciences), 2020, 52(3): 420-424.

图/表 3

表1

表2

人口统计学信息和基本资料"

Items	Death group(n=13)	Survival group(n=81)	t/Z/χ²	P
General information
Age/years, M(IQR)	77.0 (67.5, 83.0)	66.0 (59.0, 72.5)	-2.894	0.731
Male, n(%)	8 (61.5)	37 (45.7)	1.129	0.288
Vital signs on admission
Heart rate/(beats/min), $x ?$ ±s	103.2±15.8	88.4±16.7	2.997	0.004
Systolic pressure/mmHg, M(IQR)	135.0 (109.0, 161.5)	140.0 (125.0, 149.5)	-0.526	0.599
Diastolic pressure (mmHg), $x ?$ ±s	84.6±15.7	84.0±13.1	0.156	0.876
Respiratory rate/(beats/min), M(IQR)	29.0 (24.0, 30.0)	20.0 (20.0, 24.0)	-3.689	<0.001
SpO₂/%, M(IQR)	89.0 (78.5, 94.5)	96.0 (94.0, 98.0)	-3.232	1.000
Complete blood count
WBC (×10⁹/L), M(IQR)	10.2 (6.3, 14.7)	5.6 (4.5, 7.8)	-3.242	1.000
Neutrophil (×10⁹/L), M(IQR)	9.2 (5.5, 13.9)	3.8 (2.7, 5.9)	-3.510	<0.001
Lymphocyte (×10⁹/L), M(IQR)	0.5 (0.3, 0.7)	1.1 (0.7, 1.5)	-3.719	<0.001
Creatinine/(μmol/L), M(IQR)	86.0 (73.5, 112.5)	74.0 (57.0, 92.0)	-1.807	0.073
Biomarkers of myocardial injury
CK-MB/(μg/L), M(IQR)	3.2 (2.3, 6.9)	0.8 (0.5, 1.0)	-4.196	<0.001
hs-cTNⅠ/(ng/L), M(IQR)	217.2 (34.4, 4037.4)	4.9 (2.5, 13.9)	-4.513	<0.001
NT-proBNP/(μg/L), M(IQR)	945.0 (518.5, 3 464.0)	154.0 (75.0, 415.3)	-4.111	<0.001
Myocardial injury, n(%)	10 (76.9)	13 (16.0)	22.461	<0.001
Cytokines
Ferritin/(μg/L), M(IQR)	770.2 (598.0, 2 172.0)	622.8 (385.3, 1 162.7)	-2.180	0.050
IL-2R/(U/mL), M(IQR)	1 586.0 (1 253.0, 2 364.0)	694.0 (425.0, 1 054.5)	-3.740	<0.001
IL-6/(ng/L), M(IQR)	82.3 (37.8, 164.8)	13.0 (4.0, 39.4)	-3.960	<0.001
IL-8/(ng/L), M(IQR)	29.1 (16.2, 52.4)	12.4 (7.0, 21.3)	-2.551	0.160
IL-10/(ng/L), M(IQR)	9.8 (6.8, 17.9)	5.0 (5.0, 5.5)	-4.376	<0.001
TNF-α/(ng/L), M(IQR)	13.3 (7.2, 17.4)	8.8 (5.7, 12.3)	-2.202	0.051

表2

表3

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Items	Death group (n=13)	Survival group (n=81)
Hypertension	7	47
Diabetes	2	3
CHD	0	6
Hypertension & diabetes	1	13
Hypertension & CHD	1	4
Diabetes & CHD	1	1
Hypertension & diabetes & CHD	1	7

Items	Univariate analysis		Multivariate analysis
Items	OR(95%CI)	P	OR(95%CI)	P
Age/years	1.11 (1.03, 1.19)	0.004	1.18 (1.02, 1.36)	0.026
Male	1.90 (0.57, 6.32)	0.293	0.16 (0.02, 1.55)	0.113
Hypertension (No vs. Yes)	0.47 (0.11, 2.00)	0.307
Diabetes (No vs. Yes)	1.48 (0.44, 5.00)	0.524
CHD (No vs. Yes)	1.05 (0.26, 4.23)	0.945
SpO₂/%	0.89 (0.83, 0.96)	0.001	0.85 (0.72, 0.99)	0.041
Neutrophil (×10⁹/L)	1.05 (0.98, 1.11)	0.155
Lymphocyte (×10⁹/L)	0.03 (0.00, 0.30)	0.003
Creatinine/(μmol/L)	1.00 (0.99, 1.01)	0.897
Myocardial injury	17.44 (4.21, 72.1)	<0.001	11.77 (0.93, 148.87)	0.057
Ferritin>400 μg/L	5.36 (0.66, 43.48)	0.116
IL-2R>710 U/mL	5.64 (1.18, 27.05)	0.031
IL-6>35 ng/L	8.40 (2.12, 33.33)	0.002
IL-8>62 ng/L	4.73 (0.71, 31.52)	0.109
IL-10>9.1 ng/L	14.60 (3.84, 55.46)	<0.001	101.93 (4.74, 2 190.71)	0.003
TNF-α>8.1 ng/L	1.71 (0.49, 6.02)	0.402