Soluble ACE2 and angiotensin II levels are modulated in hypertensive COVID-19 patients treated with different antihypertension drugs

Figures & data

Table 1. Age, body mass index (BMI), length of stay at the hospital, levels of angiotensin-converting-enzyme-2 (ACE2) angiotensin II, C-reactive protein (CRP), D-dimer, and troponin in hypertensive COVID-19 patients treated with ACE inhibitors (ACEi), angiotensin receptor blockers (ARB), beta-blockers (BB) and calcium channel blockers (CCB).

	Total (n = 200)	ACEi (n = 57)	ARB (n = 68)	BB (n = 15)	CCB (n = 30)	P value
Age (years)	56.2 (11.6)	55.7 (10.9)	59.7 (12)	55.4 (11.3)	51.4 (10.1)	0.009*
BMI (kg/m^2)	30.3 (5.3)	30.4 (4.7)	30.2 (5.5)	32.6 (6.5)	29.2 (4.8)	0.2536
Hospital Duration (days)	14.1 (8.7)	13.3 (7)	16.1 (10.7)	10.2 (5.3)	13.3 (7.3)	0.05*
ACE2 (pg/ml)	423.8 (610.7)	269.3 (267.1)	449.4 (597.4)	294.1 (257.3)	630.2 (947.4)	0.008*
Angiotensin II (pg/ml)	2784.8 (1471.2)	2490.2 (1013.4)	3239.6 (1873.6)	2844.3 (946.8)	2266.8 (1061.2)	0.005*
CRP (mg/L)	42.1 (58.1)	30.1 (52.6)	44.0 (50.4)	36.9 (31.8)	66.2 (79.0)	0.0474*
D-dimer (mg/L)	1.8 (7.8)	2.6 (8.5)	0.64 (0.88)	6.1 (21.6)	1.9 (5.2)	0.1388
Troponin (ng/ml)	21.1 (75.8)	20.1 (44.2)	10.9 (13.8)	7.9 (6.2)	15.3 (24.2)	0.5642
Lymphocytes (x10^3/µL)	1.5 (0.85)	1.8 (1.1)	1.3 (0.69)	1.6 (0.67)	1.4 (0.58)	0.0119*
Procalcitonin	0.29 (0.76)	0.36 (1.1)	0.19 (0.35)	0.22 (0.25)	0.26 (0.31)	0.7993
Hemoglobin	14.1 (7.7)	15.8 (14.2)	13.1 (1.6)	13.0 (1.4)	13.8 (1.6)	0.2725
Systolic blood pressure	133.8 (17.9)	134.9 (17.5)	134.1 (19.6)	130.3 (19.4)	133.9 (16.4)	0.8211
Diastolic blood pressure	80.5 (10.7)	81.3 (12.0)	78.7 (10.7) s	78.6 (9.9)	84.5 (9. 1)	0.0668
Comorbidities
Diabetes mellites	129 (64.5%)	41 (71.9%)	47 (69.1%)	10 (66.7%)	20 (66.7%)
Coronary artery disease	24 (12.0%)	11 (19.3%)	7 (10.3%)	4 (26.7%)	2 (6.7%)
Congestive heart failure	11 (5.5%)	5 (8.8%)	3 (4.4%)	1 (6.7%)	1 (3.3%)
Chronic kidney disease	11 (5.5%)	2 (3.5%)	3 (4.4%)	2 (13.3%)	5 (16.7%)
Solid tumours	9 (4.5%)	2 (3.5%)	5 (7.4%)	1 (6.7%)	1 (3.3%)
Myocardial infarction	8 (4.0%)	4 (7.0%)	3 (4.4%)	–	–
Asthma	7 (3.5%)	2 (3.5%)	4 (5.9%)	–	–
End-stage renal disease	7 (3.5%)	1 (1.8%)	3 (4.4%)	1 (6.7%)	1 (3.3%)
Hypothyroidism	7 (3.5%)	2 (3.5%)	3 (4.4%)	–	1 (3.3%)
Peripheral vascular disease	5 (2.5%)	2 (3.5%)	–	2 (13.3%)	1 (3.3%)
Parkinsonism	3 (1.5%)	2 (3.5%)	–	–	–
Dyslipidemia	3 (1.5%)	1 (1.8%)	2 (2.9%)	–	–
cerebrovascular accident	2 (1.0%)	1 (1.8%)	1 (1.5%)	–	1 (3.3%)
Chronic obstructive pulmonary disease	1 (0.5%)	1 (1.8%)	–	–	–
Lymphoma	1 (0.5%)	–	1 (1.5%)	–	–
Others**	11 (5.5%)	3 (5.3%)	7 (10.3%)	1 (6.7%)	–
Comedications
COVID-19 medications	173 (86.5%)	47 (82.5%)	60 (88.2%)	15 (100%)	20 (66.7%)
Azithromycin	106	32	37	10	14
Lopinavir	63	19	21	4	8
Dexamethasone	51	15	31	2	9
Hydroxychloroquine	41	15	12	4	2
Remdesivir	25	11	18	1	4
Tocilizumab	15	4	8	–	–
Oseltamivir	5	2	1	1	–

Data are expressed as mean (SD). Differences between groups were tested by ANOVA. A p-value with a significance level of 0.05 was used. Comorbidities are expressed as the total number of patients with the condition (%). *P-value ≤ 0.05.

**Others: anxiety, familial Mediterranean fever (FMF), gout, Hepatitis B virus (HBV), osteoporosis, deep vein thrombosis and pulmonary embolism (DVT/PE), Primary hyperparathyroidism, Hepatitis C disease, renal transplant, Rheumatoid arthritis, seizure.

Figure 1. Circulating ACE2 (A) and angiotensin II (B) levels in COVID-19 hypertensive patients grouped according to disease severity (mild, moderate, and severe). Data are presented as dot plots with the mean (95% CI). Differences in log-transformed ACE2 and angiotensin II were assessed by ANOVA, *p < 0.05, **p < 0.01.

Figure 2. Circulating ACE2 and angiotensin II levels in COVID-19 hypertensive patients grouped according to two (ACEi/ARB, non-ACEi/ARB) (A, B) or four (ACEi, ARB, BB, and CCB) (C, D) medication groups. Differences in log-transformed ACE2 and angiotensin II were assessed by ANOVA, followed by Tukey's post-hoc analysis. *p < 0.05.

Figure 3. Circulating ACE2 (A) and angiotensin II levels (B) in hypertensive patients with different COVID-19 severity (mild, moderate, or severe) under each medication group (ACEi, ARB, BB, and CCB). Differences in ACE2 and angiotensin II levels were assessed by a linear regression model. *p < 0.05, **p < 0.01.

Figure 4. Comparing the percentage of hypertensive patients with different COVID-19 severity under each treatment group. The distribution of patients was compared using the Chi-square test. *p < 0.05, ****p < 0.0001.