Population
A total of 180 patients were initially screened for the study, and 47 patients younger than 60 years old were excluded. According to the clinical diagnosis and/or medical history on admission, the 133 patients were divided into two groups: hypertension patients (n = 79) and non-hypertension patients (n = 54) (Fig. 1). A total of 36 (27.1%) patients were defined as adverse clinical outcomes, including ICU admission (n = 34, 25.6%) and in-hospital death (n = 16, 12.0%, of which 14 had overlapping with ICU patients).
The difference of general conditions between hypertension and non-hypertension patients
The median age was 68 years (IQR, 64–73 years) and 68 cases (51.1%) were male in this study (Table 1). Hypertension (n = 79, 59.4%), diabetes (n = 57, 42.9%), and coronary atherosclerotic heart disease (n = 18, 13.5%) were the three most common comorbidities. Cough (n = 114, 85.7%), fever (n = 109, 82.0%), and shortness of breath (n = 88, 66.2%) were the three most common symptoms (Table 1).
Table 1
Demographics and symptomatic characteristics of patients with COVID-19
|
Total
|
Hypertension
|
Non-hypertension
|
P value
|
(n = 133)
|
(n = 79)
|
(n = 54)
|
Age, median (IQR)
|
68(64–73)
|
69(64–75)
|
67(63–71)
|
0.122
|
Gender
|
|
|
|
0.221
|
Male
|
68(51.1%)
|
44(55.9%)
|
24(44.4%)
|
|
Female
|
65(48.9%)
|
35(44.3%)
|
30(55.6%)
|
|
Smoking history
|
9(7.1%)
|
8(10.8%)
|
1(1.9%)
|
0.062
|
Cluster disease
|
11(8.3%)
|
7(8.9%)
|
4(7.4%)
|
0.765
|
Diagnosis method
|
|
|
|
0.119
|
RT-PCR
|
114(85.7%)
|
65(82.3%)
|
49(90.6%)
|
|
Gene
|
1(0.8%)
|
0(0.0%)
|
1(1.9%)
|
|
Clinical diagnosis
|
18(13.5%)
|
14(17.7%)
|
4(7.4%)
|
|
Comorbidities
|
|
|
|
|
Hypertension
|
79(59.4%)
|
79(100.0%)
|
0(0.0%)
|
/
|
Diabetes
|
57(42.9%)
|
41(51.9%)
|
16(29.6%)
|
0.013
|
CHD
|
18(13.5%)
|
13(16.5%)
|
5(9.3%)
|
0.233
|
Cerebrovascular disease
|
10(7.5%)
|
8(10.1%)
|
2(3.7%)
|
0.168
|
Liver disease
|
3(2.3%)
|
2(2.5%)
|
1(1.9%)
|
0.795
|
Kidney disease
|
5(3.8%)
|
4(5.1%)
|
0(0.0%)
|
0.407
|
COPD
|
4(3.0%)
|
2(2.5%)
|
2(3.7%)
|
0.698
|
Malignancy
|
7(5.3%)
|
4(5.1%)
|
3(5.6%)
|
0.901
|
Signs and symptoms
|
|
|
|
|
Fever
|
109(82.0%)
|
62(78.5%)
|
47(87.0%)
|
0.255
|
Cough
|
114(85.7%)
|
70(88.6%)
|
44(81.5%)
|
0.249
|
Expectoration
|
23(17.3%)
|
19(24.1%)
|
4(7.4%)
|
0.013
|
Rhinorrhoea
|
3(2.3%)
|
1(1.3%)
|
2(3.7%)
|
0.325
|
Haemoptysis
|
1(0.8%)
|
1(1.3%)
|
0(0.0%)
|
0.407
|
Shortness of breath
|
88(66.2%)
|
54(68.4%)
|
34(63.0%)
|
0.519
|
Fatigue
|
86(64.7%)
|
46(58.2%)
|
40(74.1%)
|
0.060
|
Myalgia
|
52(39.1%)
|
24(30.4%)
|
28(51.9%)
|
0.013
|
Diarrhoea
|
13(9.8%)
|
9(11.4%)
|
4(7.4%)
|
0.447
|
Nausea and vomiting
|
12(9.0%)
|
8(10.1%)
|
4(7.4%)
|
0.447
|
Arrhythmias
|
8(6.0%)
|
6(7.6%)
|
2(3.7%)
|
0.354
|
Palpitation
|
4(3.0%)
|
2(2.5%)
|
2(3.7%)
|
0.698
|
Dizziness
|
5(3.8%)
|
4(5.1%)
|
1(1.9%)
|
0.339
|
Headache
|
4(3.0%)
|
1(1.3%)
|
3(5.6%)
|
0.155
|
Abbreviation: IQR, interquartile range; RT-PCR, reverse transcription-polymerase chain reaction; CHD, coronary atherosclerotic heart disease; COPD, chronic obstructive pulmonary diseases
|
There was no difference in age, gender, smoking history and diagnostic methods between hypertension and non-hypertension patients (P > 0.05). Among all comorbidities, only diabetes had a statistically significant difference between hypertension and non-hypertension patients (P < 0.01). Of all the symptoms recorded, only expectoration and myalgia had statistically significant differences between hypertension and non-hypertension patients (P < 0.01) (Table 1).
The difference of clinical laboratory between hypertension and non-hypertension patients
Except c-reactive protein (CRP) and D-dimer, mean levels of other indices of the 133 patients were in normal range (Table 2). All BG indices, kidney function (urea nitrogen, BUN), nutrition (albumin), myocardial enzyme (creatine kinase-MB, lactate dehydrogenase), inflammatory indices (CRP, white blood cell count, neutrophil percentage, neutrophil count, lymphocyte percentage), hemoglobin, coagulation indices (prothrombin time, PT) were significantly higher in hypertension patients than non-hypertension patients (P < 0.05). Other blood routine examination (lymphocyte count et al.) and biochemical detection (liver function et al.) in the hypertension group were inferior to the non-hypertension group (P < 0.05) (Table 2).
Table 2
Laboratory parameters of patients with COVID-19
|
Reference values
|
Total (n = 133)
|
Hypertension (n = 79)
|
Non-hypertension (n = 54)
|
P value
|
Blood glucose
|
|
|
|
|
|
Maximum BG, median (IQR), mmol/L
|
3.9–6.11
|
5.61(4.93-14.40)
|
9.06(5.06-17.20)
|
5.16(4.80-7.28)
|
0.001
|
Average BG at the day of admission, median (IQR), mmol/L
|
3.9–6.11
|
5.38(4.80-8.86)
|
7.07(4.84-11.04)
|
5.06(4.71-7.28)
|
0.005
|
Biochemical detection
|
|
|
|
|
|
Total protein, median (IQR), g/L
|
65–85
|
61.10(57.35-65.65)
|
60.90(57.20-63.90)
|
61.40(58.35-67.15)
|
0.245
|
ALT, median (IQR), IU/L
|
7–40
|
23.95(16.55-41.00)
|
23.90(17.40-41.00)
|
24.20(15.40-41.05)
|
0.753
|
AST, median (IQR), IU/L
|
7–45
|
23.30(16.75-34.15)
|
24.60(18.40-37.05)
|
21.90(15.25-28.20)
|
0.070
|
Albumin, median (IQR), g/L
|
40–55
|
33.40(30.30-36.60)
|
32.90(29.40-36.30)
|
34.15(30.96-37.55)
|
0.042
|
BUN, median (IQR), mmol/L
|
2.6–7.5
|
5.12(4.05-6.85)
|
5.75(4.33-8.34)
|
4.60(3.82-5.62)
|
<0.001
|
Creatinine, median (IQR), μmol/L
|
41–73
|
67.45(56.78-80.75)
|
68.90(58.13-83.53)
|
64.15(54.05-74.28)
|
0.080
|
Uric acid, median (IQR), μmol/L
|
142–340
|
258.00(190.50-329.00)
|
273.00(180.00-341.00)
|
233.00(199.00-303.50)
|
0.410
|
Total bile acid, median (IQR), μmol/L
|
0–10
|
3.75(2.53-5.60)
|
4.30(2.50-6.05)
|
3.50(2.70-5.50)
|
0.331
|
Creatine kinase, median (IQR), IU/L
|
24–170
|
43.20(29.15-72.80)
|
44.60(31.30-74.70)
|
40.60(26.60-65.80)
|
0.171
|
Creatine kinase-MB, median (IQR), IU/L
|
0–24
|
10.00(7.05-12.95)
|
10.80(8.15-14.25)
|
7.95(6.13-11.65)
|
<0.001
|
LDH, median (IQR), IU/L
|
120–250
|
212.80(173.93-326.55)
|
257.80(185.05-382.50)
|
190.70(167.15-250.45)
|
<0.001
|
Inflammatory indices
|
|
|
|
|
|
CRP, median (IQR), mg/L
|
0–4
|
8.97(2.41-53.58)
|
16.03(2.71-81.70)
|
6.37(1.96-21.00)
|
0.021
|
Blood routine examination
|
|
|
|
|
|
White blood cell count, median (IQR), ×109/L
|
3.5–9.5
|
6.35(4.70-8.35)
|
6.90(5.20-9.00)
|
5.70(4.15-7.25)
|
0.011
|
Neutrophil percentage, mean ± SD, %
|
40–75
|
70.15±14.67
|
70.97±15.05
|
65.95±12.98
|
0.021
|
Lymphocyte percentage, mean ± SD, %
|
20–50
|
20.85±12.02
|
19.90±11.91
|
23.99±11.78
|
0.023
|
Neutrophil count, median (IQR), ×109/L
|
1.8–6.3
|
4.55(2.85-6.77)
|
5.15(3.30-7.21)
|
3.63(2.32-5.45)
|
<0.001
|
Lymphocyte count, median (IQR), ×109/L
|
1.1–3.2
|
1.18(0.75-1.64)
|
1.08(0.65-1.60)
|
1.24(0.94-1.67)
|
0.170
|
Monocyte count, mean ± SD, ×109/L
|
0.1–0.6
|
0.47±0.23
|
0.47±0.20
|
0.47±0.20
|
0.920
|
Eosinophil count, median (IQR), ×109/L
|
0.02–0.52
|
0.06(0.03-0.12)
|
0.05(0.02-0.12)
|
0.06(0.03-0.11)
|
0.689
|
Hemoglobin, mean ± SD, g/L
|
130–175
|
121.59±17.75
|
125.19±18.49
|
120.03±12.95
|
0.025
|
Platelet count, mean ± SD, ×109/L
|
125–350
|
242.02±94.16
|
228.30±92.87
|
242.39±93.06
|
0.195
|
Coagulation indices
|
|
|
|
|
|
PT, median (IQR), seconds
|
9.2–15
|
13.32(12.44-14.38)
|
13.73(12.61-14.99)
|
13.12(12.10-13.85)
|
0.012
|
APPT, median (IQR), seconds
|
21–37
|
27.96(25.60-30.19)
|
28.15(25.59-30.15)
|
27.65(25.65-30.38)
|
0.586
|
D-dimer, median (IQR), mg/L
|
0–0.55
|
0.78(0.45-2.90)
|
0.82(0.50-2.76)
|
0.70(0.37-2.91)
|
0.384
|
Abbreviation: IQR, interquartile range; ALT, alanine aminotransferase; AST, aspartate aminotransferase; BUN, urea nitrogen; LDH, lactate dehydrogenase; CRP, C-reactive protein; PT, prothrombin time; APPT, activated partial thromboplastin time
|
The difference of adverse clinical outcomes between hypertension and non-hypertension patients
There were 49.4% hypertension patients with mild to moderate symptoms and 50.6% with severe symptoms, compared to the 88.9% non-hypertension patients with mild to moderate symptoms and 11.1% with severe symptoms (Fig. 2A a-b). K-M analysis were performed to calculate the percent of clinical outcomes between hypertension group and non-hypertension group. At the last follow-up visit, 31 patients in the hypertension group (39.2%, in which 24.0% of on death in ICU and 15.2% of death) and 5 in the non-hypertension group (9.3%, in which 1.9% of on death in ICU, 7.4% of death) had adverse clinical outcomes (Fig. 2A c-d), and the overall clinical outcomes rates in the two groups differed significantly on the basis of the stratified log-rank test. It showed 32.91% (at 30 days) and 39.24% (at 60 days) adverse clinical outcomes in hypertension patients, compared to the 7.41% (at 30 days) and 9.26% (at 60 days) in non-hypertension patients. The adverse event in hypertension patients began to increase sharply at about 5 days and relaxed after 30 days. And it reached the platform at about 45 days (Fig. 2B).
Risk factors of adverse clinical outcomes in elderly COVID-19 patients
Univariate Cox hazard analysis was used to screen for statistically significant variables associated with adverse clinical outcomes. In the total population, hypertension (HR 4.937) and diabetes (HR 5.821) were the most significantly two risk factors related with adverse clinical outcomes. Average BG, BUN, neutrophil percentage, neutrophil count, maximum BG, white blood cell count, PT were the following 8 risk factors with HR range from 1.085–1.154 (Table 3). The Cox hazard analysis also showed that the top 10 risk factors of univariate Cox analysis in hypertension group were the same with that of total population only different in rank order (Table 3). Multivariate Cox-proportional hazard model analysis was conducted to further certify whether above variables got from univariate Cox affected patient clinical outcomes independently. The results demonstrated hypertension was the most important independent factor that relates with higher adverse clinical outcomes (HR 3.202, 95% CI:1.164–8.807; Fig. 3); and other significantly risk factors include low lymphocyte count, hemoglobin, CRP, LDH and platelet count.
Table 3. Univariate Cox hazard analysis to further certify whether variables affected patient clinical outcomes (Only if P < 0.05 is listed in the table)
Abbreviation: BG, blood glucose; ALT, alanine aminotransferase; AST, aspartate aminotransferase; BUN, urea nitrogen; LDH, lactate dehydrogenase; CRP, C-reactive protein; PT, prothrombin time
The cut-off value of blood pressure related with adverse clinical outcomes in elderly hypertension COVID-19 patients
The hypertension population were divided into 3 subgroups according to their blood pressure level. 40.5% had a maximum SBP of higher than 160mmHg; and 49.4% had a maximum DBP of higher than 90mmHg. (Fig. 4A).
Significant difference of clinical outcomes could be seen among different SBP subgroups in the hypertensive group. The difference of overall clinical outcomes was not statistically between the SBP (1) subgroup and the SBP (2) subgroup (P = 0.412 by the log-rank test), but was statistically between the SBP (1) subgroup and the SBP (3) subgroup (P = 0.002 by the log-rank test). There were 11.11% (at both 30 days and 60 days) cases with adverse clinical outcomes in SBP subgroup (1), 13.79% (at 30 days) and 20.69% (at 60 days) cases in SBP subgroup (2), 53.12% (at 30 days) and 71.87% (at 60 days) cases in SBP subgroup (3). At the same time, the difference of overall clinical outcomes between the DBP (1) subgroup and the DBP (2) subgroup (P = 0.005 by the log-rank test) or the DBP (3) subgroup (P = 0.02 by the log-rank test) was statistically. There were 17.50% (at 30 days) and 22.50% (at 60 days) patients with adverse clinical outcomes in the DBP subgroup (1), 47.83% (at 30 days) and 52.17% (at 60 days) patients in the DBP subgroup (2), 37.5% (at 30 days) and 62.5% (at 60 days) patients in the DBP subgroup (3). The difference among maximum SBP and DBP subgroups all increased sharply at about 5 days and continued over time, the increase was most pronounced at 30 days, and reached the platform at about 45 days (Fig. 4B).
The results of multivariate Cox-proportional hazard model analysis showed that maximum SBP (3), maximum DBP (2) and maximum BG were the independent risk factors of adverse clinical outcomes in hypertension population (Fig. 4C).