Angiotensin converting enzymes inhibitors or angiotensin receptor blockers should be continued in COVID-19 patients with hypertension

doi:10.12998/wjcc.v9.i1.47

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Retrospective Cohort Study

World J Clin Cases. Jan 6, 2021; 9(1): 47-60
Published online Jan 6, 2021. doi: 10.12998/wjcc.v9.i1.47

Table 1 Patients’ characteristics and differences between discontinued angiotensin converting enzymes inhibitors or angiotensin receptor blockers group and other anti-hypertensive drugs group

Characteristic		Patients with both COVID-19 and hypertension		χ²/z	P value
Characteristic	Total (n = 53)	Discontinued ACEIs/ARBs (n = 27)	Other anti-hypertensive drugs (n = 26)	χ²/z	P value
Male sex, n (%)	26 (49.1)	15 (57.7)	11 (42.3)	0.930	0.335
Age, median yr (IQR)	67 (59, 73)	64 (55, 72)	70 (66, 73)	-2.369	0.018
Initial symptom, n (%)
Fever (temperature ≥ 37.3 °C)	35 (66)	19 (54.3)	16 (45.7)	6.895	0.186¹
Cough	12 (22.6)	4 (33.3)	8 (66.7)
Dyspnea	1 (1.9)	0 (0)	1 (100)
Chest tension	1 (1.9)	0 (0)	1 (100)
Exhausted	1 (1.9)	1 (100)	0 (0)
Anorexia	1 (1.9)	1 (100)	0 (0)
Diarrhea	2 (3.8)	2 (100)	0 (0)
Severity of illness, n (%)
Moderate	24 (45.3)	12 (50)	12 (50)	0.016	0.901
Severe	29 (54.7)	15 (51.7)	14 (48.3)
qSOFA score, n (%)
0	26 (49.1)	17 (65.4)	9 (34.6)	4.259	0.039
≥ 1	27 (50.9)	10 (37)	17 (63)
CURB-65 score, n (%)
0	17 (32.1)	12 (70.6)	5 (29.4)	3.874	0.145¹
1	28 (52.8)	12 (42.9)	16 (57.1)
≥ 2	8 (15.1)	3 (37.5)	5 (62.5)
Comorbidities, n (%)
Diabetes	21 (39.6)	10 (47.6)	11 (52.4)	0.154	0.695
Coronary heart disease-	13 (24.5)	8 (61.5)	5 (38.5)	0.774	0.379
Duration of hypertension, median-yr (IQR)	10 (5,16)	10 (6, 20)	10 (5, 10)	1.811	0.707
Chest CT results, n (%)
Bilateral lesions	48 (90.6)	24 (50)	24 (50)	0	1
Ground glass	32 (60.4)	15 (46.9)	17 (53.1)	0.535	0.465
Consolidation	6 (11.3)	4 (66.7)	2 (33.3)	0.148	0.701
Hydrothorax	5 (9.4)	2 (40)	3 (60)	0.002	0.965
Patch shadow	37 (69.8)	19 (51.4)	18 (48.6)	0.008	0.928
Laboratory tests, median (IQR)
White blood cell count, × 10⁹/L	5.23 (4.56, 6.46)	5.22 (4.28, 6.99)	5.41 (4.76, 6.01)	-0.285	0.776
Lymphocyte count, × 10⁹/L	0.99 (0.68, 1.49)	0.81 (0.61, 1.5)	1.05 (0.78, 1.49)	-1.228	0.219
Platelet count, × 10⁹/L	247 (209, 285)	250 (202, 319)	247 (217, 280)	1.087	0.852
Hemoglobin, g/L	122 (115, 130)	122 (115, 129)	122 (115, 132)	-0.142	0.887
Alanine transaminase, U/L	21 (15, 31)	21 (14, 31)	20 (15, 30)	-0.027	0.979
Albumin, g/L	34.9 (31.3, 38.3)	33.4 (30.1, 35.9)	36.4 (31.7, 39)	-2.127	0.033
Total bilirubin, µmol/L	9.5 (7, 13.4)	9.1 (6.4, 13.4)	10.2 (7.4, 14.1)	-0.881	0.378
LDH, µmol/L	265 (228 ,313)	290 (228, 367)	262 (224, 300)	1.174	0.240
BUN, mmol/L	4.6 (3.4, 5.9)	4.6, (3.9, 6)	4.5 (3.2, 5.7)	0.854	0.393
Creatinine, µmol/L	71 (58, 90)	68 (59, 90)	71.5 (58, 90)	0.089	0.929
Prothrombin time, s	13.9 (13.2, 14.4)	13.8 (13.2, 14.3)	14 (13.2, 14.6)	-0.633	0.527
APTT, s	40.2 (35.6, 43.7)	40.8 (36.8, 44.6)	37.7 (35.3, 43.5)	1.148	0.251
Fibrous protein, g/L	4.81 (4, 6.18)	4.73 (4, 6.98)	4.85 (3.72, 6)	0.534	0.593
D-dimer, µg/L	0.93 (0.48, 1.77)	0.75 (0.47, 1.69)	1.11 (0.48, 1.81)	-0.409	0.682
hs-CRP, mg/L	21.2 (1.2, 81.4)	27.2 (5, 97.5)	16.6 (0.8, 57.9)	1.130	0.258
Procalcitonin, ng/mL	0.04 (0.02, 0.08)	0.04 (0.02, 0.06)	0.04 (0.02, 0.09)	0.290	0.772
Serum ferritin, µg/L	486 (328.35, 1023.85)	601.15 (387, 1173.3)	438.35 (321.4, 767.2)	1.244	0.213
IL-2R, U/mL	669 (445.5, 1013.5)	684.5 (488, 1172)	669 (407, 1010)	0.522	0.602
IL-6, pg/mL	8.76 (3.08, 37.12)	10.23 (3.91, 40.54)	7.66 (3.08, 34.24)	0.439	0.660
IL-8, pg/mL	13.35 (5.75, 23.2)	17.55 (7.4, 27.2)	10.4 (5.3, 18.9)	1.395	0.163
IL-10, pg/mL	5 (5, 5.45)	5 (5, 7.6)	5 (5, 5)	2.463	0.014²
hs-TnI, pg/mL	3.6 (2.9, 5.3)	4.5 (2.3, 7.6)	3.6 (3.6, 3.6)	1.090	0.267
Myoglobin, ng/mL	51.6 (37.8, 90)	50.7 (40, 134.6)	55.5 (31.8, 86.3)	0.365	0.715
CKMB, ng/mL	1.1 (0.5, 1.7)	1.2 (0.5, 1.9)	0.8 (0.5, 1.5)	0.508	0.611
NT-ProBNP, pg/mL	142.0 (71.0, 308.0)	113.0 (57.0, 311.0)	179.5 (75,0, 290.0)	-1.005	0.315
Time from onset to admission, median day (IQR)	14 (10, 18)	15 (10, 18)	12 (9, 18)	0.919	0.358

Only one patient's organ failure assessment (QSOFA) was 2, QSOFA for all other patients was 0 or 1. Therefore, QSOFA was involved as a binary variable (0, ≥1) in univariate and multivariate Cox proportional hazard model. ¹Chi-square test for continuity correction. ²Mean rank in the discontinued angiotensin converting enzymes inhibitors or angiotensin receptor blockers (ACEIs/ARBs) group = 30.73—slightly higher than that in the other anti-hypertensive drugs group (22.27). COVID-19: Coronavirus disease 2019; ACEIs/ARBs: Angiotensin converting enzymes inhibitors or angiotensin receptor blockers; qSOFA: Quick sequential organ failure assessment; LDH: Lactate dehydrogenase; BUN: Blood urea nitrogen; APTT: Activated partial thromboplastin time; hs-CRP: High-sensitive C-reactive protein; IL-2R: Interleukin-2 receptor; IL-6: Interleukin-6; IL-8: Interleukin-8; IL-10: Interleukin-10; hs-TnI: High sensitive cardiac troponin I; CKMB: Creatine phosphokinase isoenzyme; NT-ProBNP: N-terminal pro-brain natriuretic peptide; IQR: Interquartile range; CT: Computed tomography.

Table 2 Univariate Cox proportional risk model associated with each indicator and prognosis

	B	HR (95%CI)	Significance
ACEIs/ARBs	-0.289	0.749 (0.426, 1.319)	0.317
Gender	-0.516	0.597 (0.333, 1.070)	0.083
Age	-0.007	0.993 (0.961, 1.025)	0.650
Initial symptom			0.280
Fever (temperature ≥ 37.3 °C)	-0.225	0.799 (0.393, 1.623)	0.534
Cough	1.464	4.324 (0.547, 34.167)	0.165
Dyspnea	0.012	1.012 (0.137, 7.496)	0.991
Chest tension	1.811	6.115 (0.75, 49.843)	0.091
Exhaustion	1.811	6.115 (0.75, 49.843)	0.091
Anorexia	0.782	2.185 (0.286, 16.699)	0.451
Severity of illness	-0.541	0.582 (0.328, 1.032)	0.064
qSOFA score	-0.719	0.487 (0.272, 0.871)	0.015
CURB-65 score			0.178
CURB-65 (1)	-0.552	0.576 (0.305, 1.086)	0.088
CURB-65 (2)	-0.65	0.522 (0.211, 1.288)	0.158
Diabetes	-0.093	0.911 (0.512, 1.622)	0.752
Coronary heart disease	0.62	1.860 (0.953, 3.630)	0.069
Chest CT results (single and bilateral)	0.658	1.930 (0.681, 5.466)	0.216
Chest CT results (ground glass opacity)	-0.135	0.874 (0.487, 1.569)	0.652
Chest CT results (consolidation)	0.127	1.136 (0.481, 2.681)	0.772
Chest CT results (pleural effusion)	-0.976	0.377 (0.134, 1.060)	0.064
Chest CT results (patch shadow)	0.199	1.220 (0.651, 2.287)	0.534
Urine protein	-0.151	0.860 (0.466, 1.587)	0.630
Influenza antibody			0.607
Influenza A antibody	-0.305	0.737 (0.405, 1.341)	0.318
Influenza B antibody	-0.117	0.889 (0.305, 2.596)	0.830
Duration of hypertension	-0.008	0.992 (0.953, 1.032)	0.678
White blood cell count	-0.112	0.894 (0.749, 1.067)	0.216
Lymphocyte count	0.322	1.380 (0.774, 2.461)	0.275
Platelet	0.001	1.001 (0.997, 1.005)	0.651
Hemoglobin	-0.007	0.993 (0.969, 1.018)	0.576
Alanine transaminase	-0.015	0.985 (0.965, 1.005)	0.131
Albumin	0.138	1.148 (1.058, 1.246)	0.001
Total bilirubin	-0.031	0.969 (0.918, 1.024)	0.263
LDH	-0.004	0.996 (0.992, 0.999)	0.013
BUN	-0.088	0.916 (0.806, 1.041)	0.177
Creatinine	-0.01	0.990 (0.979, 1.002)	0.099
Prothrombin time	0.027	1.027 (0.895, 1.178)	0.701
APTT	-0.022	0.978 (0.944, 1.013)	0.217
Fibrous protein	-0.039	0.962 (0.794, 1.165)	0.689
BD-dimer	-0.056	0.945 (0.89, 1.004)	0.065
Bhs-CRP	-0.006	0.994 (0.989, 0.999)	0.017
B procalcitonin	-0.703	0.495 (0.069, 3.562)	0.485
B Serum ferritin	-0.001	0.999 (0.999, 1.000)	0.027
IL-1β	0.098	1.103 (0.927, 1.311)	0.268
IL-2R	-0.001	0.999 (0.998, 1.000)	0.007
IL-6	-0.002	0.998 (0.993, 1.003)	0.370
IL-10	-0.093	0.911 (0.813, 1.021)	0.108
hs-TnI	-0.016	0.984 (0.924, 1.048)	0.619
Myoglobin	-0.004	0.996 (0.993, 1.000)	0.051
CKMB	-0.037	0.964 (0.879, 1.058)	0.440
NT-ProBNP	0	1.000 (1.000, 1.000)	0.938

ACEIs/ARBs: Angiotensin converting enzymes inhibitors or angiotensin receptor blockers; qSOFA: Quick sequential organ failure assessment; LDH: Lactate dehydrogenase; BUN: Blood urea nitrogen; APTT: Activated partial thromboplastin time; hs-CRP: High-sensitive C-reactive protein; IL-1β: Interleukin-1β; IL-2R: Interleukin-2 receptor; IL-6: Interleukin-6; IL-8: Interleukin-8; IL-10: Interleukin-10; hs-TnI: High sensitive cardiac troponin I; CKMB: Creatine phosphokinase isoenzyme; NT-ProBNP: N-terminal pro-brain natriuretic peptide; IQR: Interquartile range; CT: Computed tomography; HR: Hazard ratio; CI: Confidence interval.

Table 3 Multivariate Cox proportional risk model to investigate the association between discontinuation of angiotensin converting enzymes inhibitors or angiotensin receptor blockers and prognosis

	All the objects		Stratified by admission severity
			Moderate		Severe
	HR (95%CI)	P value	HR (95%CI)	P value	HR (95%CI)	P value
ACEIs/ARBs	0.424 (0.187, 0.962)	0.040	0.224 (0.050, 0.998)	0.0497	0.793 (0.215, 2.926)	0.728
qSOFA score	0.455 (0.201, 1.026)	0.058	0.685 (0.112, 4.199)	0.682	0.576 (0.161, 2.053)	0.395
Gender	1.116 (0.527, 2.363)	0.774	0.733 (0.100, 5.368)	0.760	0.850 (0.267, 2.698)	0.782
Coronary heart disease	3.497 (1.475, 8.291)	0.004	2.207 (0.569, 8.562)	0.252	3.695 (0.933, 14.64)	0.063
Chest CT results pleural effusion	0.577 (0.187, 1.778)	0.338	0.348 (0.042, 2.871)	0.327	0.294 (0.037, 2.303)	0.244
Albumin	1.087 (0.969, 1.219)	0.153	1.110 (0.860, 1.433)	0.423	1.163 (0.970, 1.394)	0.104
LDH	0.997 (0.992, 1.002)	0.239	1.000 (0.988, 1.012)	0.982	0.995 (0.988, 1.001)	0.128
Creatinine	0.978 (0.959, 0.997)	0.026	0.958 (0.920, 0.997)	0.036	0.993 (0.964, 1.023)	0.660
D-dimer	0.972 (0.907, 1.043)	0.431	0.489 (0.147, 1.624)	0.243	0.963 (0.889, 1.042)	0.349
hs-CRP	0.999 (0.988, 1.009)	0.793	0.993 (0.963, 1.025)	0.670	1.000 (0.985, 1.016)	0.953
Serum ferritin	1.000 (0.999, 1.001)	0.998	1.001 (0.997, 1.006)	0.600	1.001 (1.000, 1.002)	0.172
IL2R	1.000 (0.999, 1.002)	0.485	1.000 (0.998, 1.003)	0.814	1.000 (0.999, 1.002)	0.722
Myoglobin	1.002 (0.995, 1.010)	0.489	1.014 (1.002, 1.026)	0.026	0.993 (0.983, 1.003)	0.153

ACEIs/ARBs: Angiotensin converting enzymes inhibitors or angiotensin receptor blockers; qSOFA: Quick sequential organ failure assessment; LDH: Lactate dehydrogenase; hs-CRP: High-sensitive C-reactive protein; IL-2R: Interleukin-2 receptor; HR: Hazard ratio; CI: Confidence interval.

Citation: Tian C, Li N, Bai Y, Xiao H, Li S, Ge QG, Shen N, Ma QB. Angiotensin converting enzymes inhibitors or angiotensin receptor blockers should be continued in COVID-19 patients with hypertension. World J Clin Cases 2021; 9(1): 47-60
URL: https://www.wjgnet.com/2307-8960/full/v9/i1/47.htm
DOI: https://dx.doi.org/10.12998/wjcc.v9.i1.47