Characteristics of Study Population
The dataset of our study consisted of 522 CES patients with NVAF. Standard liver chemistry tests were generally in normal range of the study sample, with 11.7% of aspartate aminotransferase (AST)> 40 IU/L, 11.1% of alanine aminotransferase (ALT)>40 IU/L. Among these patients, 109, 280, 133 subjects were classified into unlikely advanced fibrosis group, indeterminate group, likely advanced fibrosis group, respectively. Patients in likely advanced fibrosis group had higher values for age, CHA2DS2-VASc score, HAS-BLED score and higher prevalence of smoking, diabetes melitus, hyperlipidemia, ischemic heart disease, P < 0.05 for both comparisons. No difference was found in sex, BMI, hypertension, prior history of ischemic stroke/TIA, drug use before admission (anticoagulant, antiplatelet and lipid-lowering use) and treatment in hospital (intravenous thrombolysis and endovascular revascularization) among three groups (Table 1).
Table1. Characteristics of Acute CES Patients with NVAF in Different FIB-4 lever
Characteristics
|
Study Sample
(N=522)
|
FIB-4 Score<1.45
(N=109)
|
(1.45-3.25)
(N=280)
|
FIB-4 Score>3.25
(N=133)
|
Patient characteristics
|
|
Mean age, y, (SD) **
|
72.61 (9.77)
|
64.81 (11.21)
|
73.55 (8.16)
|
77.03 (7.85)
|
Male sex
|
271 (51.9)
|
58 (53.2)
|
138 (49.3)
|
75 (56.4)
|
Smoker **
|
111 (21.2)
|
25 (22.9)
|
70 (25.0)
|
16 (12.0)
|
Risk stratification
|
CHA2DS2-VASc score**
|
3 (2-4)
|
3 (2-4)
|
3 (2-4)
|
3 (3-4)
|
HAS-BLED score**
|
1 (1-2)
|
1 (0-2)
|
1 (1-2)
|
2 (1-2)
|
Diabetes mellitus*
|
127 (24.3)
|
28 (25.7)
|
76 (27.1)
|
23 (17.3)
|
Hypertension
|
343 (65.7)
|
68 (62.4)
|
185 (66.1)
|
90 (67.7)
|
hyperlipidemia**
|
122 (23.4)
|
35 (32.1)
|
61 (21.8)
|
26 (19.5)
|
Ischemic heart disease**
|
120 (23.0)
|
19 (17.4)
|
63 (22.5)
|
38 (28.6)
|
Prior history of Ischemic Stroke/TIA
|
88 (16.8)
|
17 (15.6)
|
54 (19.3)
|
17 (12.8)
|
Body Mass Index
|
|
|
Mean, kg/m2 , (SD)
|
22.77 (3.33)
|
22.54 (3.12)
|
22.99 (3.40)
|
22.50 (3.35)
|
Obese≥27.5kg/m2
|
41 (7.9)
|
6 (5.5)
|
26 (9.3)
|
9 (6.8)
|
Drug use before admission
|
Anticoagulant use
|
49 (9.4)
|
14 (12.8)
|
21 (7.5)
|
14 (10.5)
|
Antiplatelet use
|
173 (33.1)
|
26 (23.9)
|
102 (36.6)
|
45 (34.1)
|
Lipid-lowering use
|
119 (22.8)
|
19 (17.4)
|
63 (22.5)
|
37 (27.8)
|
Admission laboratory data
|
Platelet count, ×103 per microliter**
|
179.00 (136.75-219.00)
|
233.00 (196.00-286.00)
|
182.00 (151.25-215.00))
|
119.00 (102.00-151.00)
|
INR**
|
1.09 (1.04-1.17)
|
1.07 (1.02-1.13)
|
1.09 (1.03-1.16)
|
1.13 (1.07-1.21)
|
AST, units/L**
|
23.00 (18.00-31.00)
|
18.00 (15.00-24.35)
|
22.00 (18.00,28.75)
|
32.00 (24.00-44.50)
|
AST >40 units/L**
|
61 (11.70)
|
2 (1.8)
|
21 (7.5)
|
38 (28.6)
|
ALT, units/L
|
18.10 (12.15-27.00)
|
20.00 (13.90-30.87)
|
18.00 (12.00-25.75)
|
17.33 (12.00-26.90)
|
ALT >40 units/L
|
58 (11.1)
|
13 (11.9)
|
28 (10.0)
|
17 (12.8)
|
Albumin, g/dL
|
38.00 (35.20-41.00)
|
38.30 (35.05-42.00)
|
38.35 (35.53-40.90)
|
37.30 (34.45-40.20)
|
eGFR, ml/min/1.73m2 **
|
90.16 (80.77-104.39)
|
95.91 (88.17-119.82)
|
89.74 (80.44-102.06)
|
85.61 (76.53-
97.31)
|
Lg NT-pro BNP**
|
2.99 (2.73-3.27)
|
2.85 (2.62-3.15)
|
2.95 (2.69-3.25)
|
3.17 (2.90-3.47)
|
FIB-4 score***
|
2.28 (1.60-3.27)
|
1.18 (0.94-1.30)
|
2.19 (1.81-2.61)
|
4.42 (3.68-6.04)
|
Stroke severity on admission
|
GCS
|
15 (11-15)
|
15 (12-15)
|
15 (12-15)
|
13 (9-15)
|
NIHSS*
|
8 (3-13)
|
5 (2-12)
|
7 (3-13)
|
8 (3-15)
|
NIHSS≥8*
|
227 (43.5)
|
40 (36.7)
|
116 (41.4)
|
71 (53.4)
|
Treatment in hospital
|
Antiplatelet use*
|
230 (44.1)
|
52 (47.7)
|
126 (45.0)
|
52 (39.1)
|
Anticoagulant use*
|
292 (57.9)
|
57 (52.3)
|
154 (55.0)
|
81 (70.9)
|
Intravenous thrombolysis
|
33 (6.3)
|
9 (8.3)
|
16 (5.7)
|
8 (6.0)
|
Endovascular revascularization*
|
71 (13.6)
|
14 (12.9)
|
46 (16.4)
|
11 (8.3)
|
Outcomes at discharge
|
mRS*
|
2 (1-5)
|
2 (1-4)
|
4 (1-5)
|
5 (2-5)
|
mRS≥3**
|
208 (39.8)
|
33 (30.3)
|
100 (35.7)
|
75 (56.4)
|
All-cause death*
|
39 (7.3)
|
9 (8.2)
|
16 (5.7)
|
14 (12.3)
|
Period of hospitalization, days*
|
30 (20-40)
|
30 (20-35)
|
28 (20-35)
|
35 (21-46)
|
Data are reported as mean ± SD, median (IQR) or number and percentage. † CES, cardioembolic stroke; NVAF, nonvalvular atrial fibrillation; FIB-4, fibrosis-4 score; TIA, transient ischemic attacks; INR, international normalized ratio; AST, aspartate aminotransferase; ALT, alanine aminotransferase; eGFR, estimated glomerular filtration rate; NT-pro BNP, N-terminal Pro-B-type Natriuretic Peptide; NIHSS, National Institutes of Health Stroke Scale; mRS, modified Rankin Scale; ‡ P-values,* for P<0.05, ** for P<0.01, *** for P<0.001. |
The Associations Between FIB-4 Score and Short-term Clinical Outcomes of CES patients with NVAF
Patients with likely advanced fibrosis group had significantly worse outcomes in hospital, such as higher NIHSS score on admission and mRS score at discharge, and they usually had a higher incidence of 90-days mortality, severe stroke, major disability compared with other 2 groups, P < 0.05 for both comparisons. (Table 1).
Multivariate analysis for short-term outcomes showed that FIB-4 score levels were associated with the risk of severe stroke (OR=1.10, 95% CI: 1.07–1.21), major disability (OR=1.20, 95% CI: 1.06-1.37) and 90-days mortality (HR=1.34, 95% CI: 1.08-2.01). Furthermore, compared with no advanced fibrosis likely, likely advanced fibrosis was significantly associated with an increased risk of severe stroke (OR=2.21, 95% CI: 1.04–3.54), major disability (OR=4.59, 95% CI: 1.88-11.18) and 90-days mortality (HR=1.25, 95% CI: 1.10-1.56). Moreover, indeterminate fibrosis was also significantly associated with 90-days mortality (HR=1.16, 95% CI: 1.08-1.34), but not related severe stroke (OR=1.34, 95% CI: 0.80–2.24) and major disability (OR=1.26, 95% CI: 0.59-2.70). (Table 3, 4, 5).
Table 3. Effect Modification of Sex on the Associations Between FIB-4 and Admission Stroke Severity
FIB-4
|
Model 1
|
Model 2
|
Model 3
|
Model 4
|
OR (95% CI)
|
P value
|
OR (95% CI)
|
P value
|
OR (95% CI)
|
P value
|
OR (95% CI)
|
P value
|
Totality
|
Continuous
|
1.12 (1.04,1.22)
|
0.006
|
1.11 (1.02,1.20)
|
0.013
|
1.11 (1.01,1.20)
|
0.022
|
1.10 (1.07,1.21)
|
0.013
|
Categories
|
FIB-4<1.45
|
Reference
|
Reference
|
Reference
|
Reference
|
1.45-3.25
|
1.22 (0.77,1.93)
|
0.393
|
1.29 (0.79,2.11)
|
0.324
|
1.34 (0.80,2.24)
|
0.267
|
1.34 (0.80,2.24)
|
0.27
|
FIB-4>3.25
|
1.98 (1.17,3.31)
|
0.008
|
1.99 (1.09,3.46)
|
0.025
|
2.03 (1.11,3.72)
|
0.022
|
2.21 (1.04,3.54)
|
0.036
|
Male
|
Continuous
|
1.14 (1.01,1.29)
|
0.033
|
1.17 (1.03,1.35)
|
0.019
|
1.18 (1.02,1.35)
|
0.024
|
1.21 (1.10,1.32)
|
0.000
|
Categories
|
FIB-4<1.45
|
Reference
|
Reference
|
Reference
|
Reference
|
1.45-3.25
|
1.31 (0.68,2.50)
|
0.410
|
1.59 (0.76,3.38)
|
0.217
|
1.72 (0.80,3.72)
|
0.165
|
1.71 (0.78,3.74)
|
0.177
|
FIB-4>3.25
|
2.39
(1.08,5.05)
|
0.031
|
2.73 (1.15,6.46)
|
0.023
|
2.97 (1.19,7.42)
|
0.020
|
3.12 (1.16,7.11)
|
0.030
|
Female
|
Continuous
|
1.11 (0.99,1.24)
|
0.079
|
1.06 (0.95,1.19)
|
0.264
|
1.07 (0.95,1.21)
|
0.245
|
1.07 (0.96,1.21)
|
0.277
|
Categories
|
FIB-4<1.45
|
Reference
|
Reference
|
Reference
|
Reference
|
1.45-3.25
|
1.10 (0.57,2.10)
|
0.787
|
1.09
(0. 51,2.18)
|
0.804
|
1.12 (0.55,2.79)
|
0.760
|
1.12 (0.54,2.31)
|
0.761
|
FIB-4>3.25
|
1.80 (0.88,3.66)
|
0.107
|
1.77 (0.78,4.01)
|
0.175
|
1.88 (0.81,4.39)
|
0.145
|
1.89 (0.79,4.52)
|
0.151
|
Data are reported as mean ± SD, median (IQR) or number and percentage. † Model 1: adjusted for none. Model 2: adjusted for age, BMI. Model 3: adjusted for age, BMI, smoker (not for females), lg NT pro-BNP, eGFR, INR, antiplatelet use. Model 4: adjusted for all covariables in model 3 plus adjusted for diabetes mellitus, hypertension, hyperlipidemia, ischemic heart disease, prior history of ischemic stroke/TIA. ‡ FIB-4, fibrosis-4 score; BMI, Body Mass Index; TIA, transient ischemic attacks; INR, international normalized ratio; eGFR, estimated glomerular filtration rate; NT-pro BNP, N-terminal Pro-B-type Natriuretic Peptide; OR, odds ratio; 95% CI, 95% confidence interval. |
Table 4. Effect Modification of Sex on the Associations Between FIB-4 and major disability After CES
FIB-4
|
Model 1
|
Model 2
|
Model 3
|
Model 4
|
OR (95% CI)
|
P value
|
OR (95% CI)
|
P value
|
OR (95% CI)
|
P value
|
OR (95% CI)
|
P value
|
Totality
|
Continuous
|
1.21 (1.10,1.34)
|
0.000
|
1.19 (1.08,1.32)
|
0.001
|
1.16 (1.05,1.29)
|
0.005
|
1.20 (1.06,1.37)
|
0.004
|
Categories
|
FIB-4<1.45
|
Reference
|
Reference
|
Reference
|
Reference
|
1.45-3.25
|
1.59 (0.93,2.71)
|
0.088
|
1.61 (0.91,2.87)
|
0.104
|
1.80 (0.98,3.28)
|
0.057
|
1.26 (0.59,2.70)
|
0.552
|
FIB-4>3.25
|
3.62 (2.01,6.53)
|
0.000
|
3.51 (1.82,6.76)
|
0.000
|
3.60 (1.79,7.25)
|
0.000
|
4.59 (1.88,11.18)
|
0.001
|
Male
|
Continuous
|
1.38 (1.17,1.62)
|
0.000
|
1.48 (1.22,1.77)
|
0.000
|
1.48 (1.21,1.81)
|
0.000
|
1.82 (1.38,2.40)
|
0.000
|
Categories
|
FIB-4<1.45
|
Reference
|
Reference
|
Reference
|
Reference
|
1.45-3.25
|
1.59 (0.72,3.48)
|
0.251
|
2.67 (1.04,6.85)
|
0.047
|
2.60 (0.99,6.85)
|
0.052
|
2.67 (0.98,5.52)
|
0.078
|
FIB-4>3.25
|
3.75
(1.63,8.63)
|
0.002
|
7.97 (2.65,23.94)
|
0.000
|
7.68 (2.46,23.96)
|
0.000
|
13.21 (2.47,55.22)
|
0.000
|
Female
|
Continuous
|
1.10 (0.99,1.25)
|
0.078
|
1.07 (0.95,1.20)
|
0.258
|
1.03 (0.91,1.16)
|
0.668
|
1.04 (0.87,1.26)
|
0.649
|
Categories
|
FIB-4<1.45
|
Reference
|
Reference
|
Reference
|
Reference
|
1.45-3.25
|
1.57 (0.75,3.27)
|
0.229
|
1.33
(0. 61,2.89)
|
0.471
|
1.52 (0.67,3.42)
|
0.316
|
1.06 (0.33,3.43)
|
0.924
|
FIB-4>3.25
|
3.89 (1.64,9.22)
|
0.002
|
3.00 (1.21,7.46)
|
0.018
|
2.96 (1.12,7.81)
|
0.028
|
3.05 (0.76,12.36)
|
0.118
|
Data are reported as mean ± SD, median (IQR) or number and percentage. † Model 1: adjusted for none. Model 2: adjusted for age, BMI. Model 3: adjusted for age, BMI, smoker (not for females), lg NT pro-BNP, eGFR, diabetes mellitus, hypertension, hyperlipidemia, ischemic heart disease, prior history of ischemic stroke/TIA. Model 4: adjusted for all covariables in model 3 plus adjusted for treatment in hospital, NIHSS on admission. ‡ CES, cardioembolic stroke; FIB-4, fibrosis-4 score; BMI, Body Mass Index; TIA, transient ischemic attacks; eGFR, estimated glomerular filtration rate; NT-pro BNP, N-terminal Pro-B-type Natriuretic Peptide; NIHSS, National Institutes of Health Stroke Scale; OR, odds ratio; 95% CI, 95% confidence interval. |
Table 5. Effect Modification of Sex on the Associations Between FIB-4 and All-cause Death After CES
FIB-4
|
Model 1
|
Model 2
|
HR (95% CI)
|
P value
|
HR (95% CI)
|
P value
|
Totality
|
|
|
|
|
Continuous
|
1.21 (1.10,1.34)
|
0.001
|
1.34 (1.08,2.01)
|
0.003
|
FIB-4<1.45
|
Reference
|
Reference
|
1.45-3.25
|
1.28 (1.12,1.65)
|
0.003
|
1.12 (1.04-1.32)
|
0.000
|
FIB-4>3.25
|
1.40 (1.19,1.84)
|
0.015
|
1.25 (1.10-1.56)
|
0.001
|
Male
|
|
|
|
|
Continuous
|
1.36 (1.16,1.58)
|
0.000
|
1.44 (1.20,1.72)
|
0.000
|
Categories
|
FIB-4<1.45
|
Reference
|
Reference
|
1.45-3.25
|
1.15 (1.05, 1.67)
|
0.03
|
1.16 (1.08-1.34)
|
0.000
|
FIB-4>3.25
|
1.27 (1.10, 1.78)
|
0.005
|
1.20 (1.05-1.74)
|
0.03
|
Female
|
|
|
|
|
Continuous
|
1.13 (1.00,1.26)
|
0.054
|
1.08 (0.97,1.21)
|
0.244
|
FIB-4<1.45
|
Reference
|
Reference
|
1.45-3.25
|
1.06 (0.45, 1.40)
|
0.173
|
1.48 (0.94-1.61)
|
0.236
|
FIB-4>3.25
|
1.01 (0.38-1.86)
|
0.499
|
1.13 (1.00-1.88)
|
0.034
|
Data are reported as mean ± SD, median (IQR) or number and percentage. † Model 1: adjusted for none. Model 2: adjusted for adjusted for age, BMI, lg NT pro-BNP, eGFR, diabetes mellitus, hypertension, hyperlipidemia, ischemic heart disease, prior history of ischemic stroke/TIA, treatment in hospital, NIHSS on admission. ‡ CES, cardioembolic stroke; FIB-4, fibrosis-4 score; BMI, Body Mass Index; TIA, transient ischemic attacks; eGFR, estimated glomerular filtration rate; NT-pro BNP, N-terminal Pro-B-type Natriuretic Peptide; NIHSS, National Institutes of Health Stroke Scale; HR, hazard ratio; 95% CI, 95% confidence interval. |
Stroke Severity and Short-term Outcomes of Study Population Stratified by Sex
When stratified by sex, the likely advanced fibrosis group had higher value for age and INR both in males and females, but beyond that, the male patients had higher CHA2DS2-VASc score, HAS-BLED score and higher proportion of smoker, hyperlipidemia, intravenous thrombolysis and endovascular revascularization in likely advanced fibrosis group. No differences were observed in sex, BMI, hypertension, prior history of ischemic stroke/TIA, drug use before admission among three groups both for males and females (Table 2).
Both male and female patients in likely advanced fibrosis group had higher NIHSS score, mRS score, more severe stroke, and more major disability than their counterparts (Table 2). For 90-days mortality, 8.0% male patients suffered death in likely advanced fibrosis group, which was higher than other 2 groups, but there was no significant difference among three groups in females (Table 2).
Table 2. Characteristics of Acute CES Patients with NVAF in different FIB-4 lever, Stratified by Sex
Characteristics
|
Study Sample
|
FIB-4 Score<1.45
|
(1.45-3.25)
|
FIB-4 Score>3.25
|
Male (N)
|
N=271
|
N=58
|
N=138
|
N=75
|
Patient characteristics
|
|
Mean age, y, (SD) **
|
71.65 (10.28)
|
62.34 (12.02)
|
72.49 (8.03)
|
77.32 (7.26)
|
Smoker**
|
108 (39.9)
|
25 (42.9)
|
68 (49.2)
|
15 (20.0)
|
Risk stratification
|
CHA2DS2-VASc score*
|
3 (2-4)
|
2 (1-3)
|
3 (2-4)
|
3 (3-4)
|
HAS-BLED score*
|
1 (1-2)
|
1 (0-1)
|
1 (1-2)
|
2(1-2)
|
Diabetes mellitus
|
64 (23.6)
|
14 (24.1)
|
37 (26.8)
|
13 (17.3)
|
Hypertension
|
164 (60.5)
|
31 (53.4)
|
83 (60.1)
|
50 (66.7)
|
Hyperlipidemia**
|
53 (19.6)
|
17 (29.3)
|
26 (18.8)
|
10 (13.3)
|
Ischemic heart disease
|
72 (26.6)
|
12 (20.7)
|
38 (27.5)
|
22 (29.3)
|
Prior history of Ischemic stroke/TIA
|
45 (16.6)
|
7 (12.0)
|
27 (19.5)
|
11 (17.3)
|
Body Mass Index
|
|
Mean, kg/m2 , (SD)
|
23.30 (3.06)
|
22.71 (2.88)
|
22.63 (3.00)
|
23.15 (3.27)
|
Obese≥27.5kg/m2
|
21 (7.7)
|
2 (3.4)
|
13 (9.4)
|
6 (8.0)
|
Drug use before admission
|
Anticoagulant use
|
28 (10.3)
|
9 (12.0)
|
12 (8.7)
|
7 (12.1)
|
Antiplatelet use
|
91 (33.7)
|
15 (25.9)
|
53 (38.4)
|
23 (31.1)
|
Lipid-lowering use
|
72 (26.6)
|
12 (20.7)
|
38 (27.5)
|
22 (29.3)
|
Admission laboratory data
|
Platelet count, ×103 per microliter**
|
168.00 (132.00-209.00)
|
236.00 (191.75-288.75)
|
170.00 (147.75-203.25)
|
113.00 (102.00-139.00)
|
INR*
|
1.10 (1.05-1.19)
|
1.06 (1.01-1.14)
|
1.08 (1.00-1.18)
|
1.12 (1.07-1.24)
|
AST, units/L**
|
22.00 (18.00-39.00)
|
18.10 (14.95-25.00)
|
22.00 (17.90,28.00)
|
27.20 (22.00-38.7)
|
AST >40 units/L**
|
26 (9.6)
|
0 (0.0)
|
9 (6.5)
|
17 (22.7)
|
ALT, units/L
|
18.70 (12.50-28.00)
|
20.50 (14.50-31.15)
|
18.00 (12.23-26.25)
|
17.71 (11.00-28.00)
|
ALT >40 units/L
|
28 (10.3)
|
5 (8.6)
|
12 (8.7)
|
11 (14.7)
|
Albumin, g/dL
|
37.70 (35.10-40.80)
|
37.40 (34.60-41.50)
|
37.90 (35.40-40.70)
|
37.30 (34.45-40.60)
|
eGFR, ml/min/1.73m2 **
|
96.51 (79.15-115.60)
|
110.37 (90.47-136.23)
|
97.00 (79.02-114.49)
|
87.13 (67.55-
87.13)
|
Lg NT pro-BNP**
|
2.95 (2.70-3.21)
|
2.79 (2.57-3.09)
|
2.90 (2.56-3.16)
|
3.13 (2.89-3.47)
|
FIB-4 score***
|
2.28 (1.56-3.43)
|
1.14 (0.93-1.29)
|
2.17 (1.76-2.59)
|
4.40 (3.68-5.95)
|
Stroke severity on admission
|
GCS
|
15 (12-15)
|
15 (12-15)
|
15 (13-15)
|
15 (11-15)
|
NIHSS*
|
5 (2-13)
|
4 (2-12)
|
5 (2-13)
|
6 (3-15)
|
NIHSS≥8**
|
102 (37.6)
|
19 (32.8)
|
48 (34.8)
|
35 (46.7)
|
Treatment in hospital
|
Antiplatelet use**
|
134 (49.4)
|
34 (58.6)
|
71 (51.4)
|
29 (38.7)
|
Anticoagulant use**
|
137 (50.6)
|
24 (41.4)
|
67 (48.6)
|
46 (61.3)
|
Intravenous thrombolysis*
|
15 (5.5)
|
5 (8.6)
|
7 (5.1)
|
3 (4.0)
|
Endovascular revascularization*
|
29 (10.7)
|
7 (12.0)
|
16 (11.5)
|
6 (8.0)
|
Outcomes at discharge
|
MRS*
|
2 (1-5)
|
2 (1-4)
|
4 (1-5)
|
5 (2-5)
|
MRS≥3***
|
91 (33.6)
|
15 (25.9)
|
39 (28.3)
|
37 (49.3)
|
All-cause death*
|
14 (5.2)
|
3 (5.2)
|
5 (3.6)
|
6 (8.0)
|
Period of hospitalization, days*
|
25 (20-37)
|
22 (20-34)
|
24.5 (20-37.5)
|
27.5 (20-42)
|
Female (N)
|
N=251
|
N=51
|
N=142
|
N=58
|
Patient characteristics
|
|
Mean age, y, (SD) **
|
73.65 (9.11)
|
67.61 (9.51)
|
74.59 (8.18)
|
76.66 (8.61)
|
Smoker
|
3 (1.2)
|
0 (0)
|
2 (1.4)
|
1 (1.7)
|
Risk stratification
|
CHA2DS2-VASc score
|
4 (3-4)
|
3 (2-4)
|
4 (3-4)
|
4 (3-4)
|
HAS-BLED score
|
2 (1-2)
|
1 (1-2)
|
2 (1-2)
|
1 (1-2)
|
Diabetes mellitus
|
63 (25.3)
|
14 (27.5)
|
39 (27.5)
|
10 (17.2)
|
Hypertension
|
179 (71.3)
|
37 (72.5)
|
102 (71.8)
|
40 (69.0)
|
Hyperlipidemia
|
69 (27.5)
|
18 (35.3)
|
35 (24.6)
|
16 (27.6)
|
Ischemic heart disease*
|
48 (19.1)
|
7 (13.7)
|
25 (17.6)
|
16 (27.6)
|
Prior history of Ischemic stroke/TIA
|
43 (17.1)
|
10 (19.6)
|
27 (19.0)
|
6 (10.3)
|
Body Mass Index
|
|
Mean, kg/m2 , (SD)
|
22.2 (3.52)
|
22.36 (3.40)
|
22.37 (3.66)
|
21.66 (3.29)
|
Obese≥27.5kg/m2
|
20 (8.0)
|
4 (7.8)
|
13 (9.2)
|
3 (5.2)
|
Drug use before admission
|
Anticoagulant use
|
21 (8.4)
|
7 (13.7)
|
9 (6.3)
|
5 (8.6)
|
Antiplatelet use
|
82 (32.8)
|
11 (21.6)
|
49 (34.8)
|
22 (37.9)
|
lipid-lowering use
|
47 (18.7)
|
7 (13.7)
|
25 (17.6)
|
15 (25.9)
|
Admission laboratory data
|
Platelet count, ×103 per microliter**
|
185.00 (147.00-229.00)
|
233.00 (193.00-285.00)
|
186.50 (153.00-223.50))
|
128.00 (102.75-172.50)
|
INR*
|
1.08 (1.03-1.17)
|
1.07 (1.03-1.13)
|
1.08 (1.02-1.16)
|
1.13 (1.06-1.21)
|
AST, units/L**
|
23.75 (18.00-33.00)
|
17.00 (15.00-23.00)
|
22.00 (18.00,29.00)
|
34.56 (28.65-46.00)
|
AST >40 units/L**
|
35 (13.9)
|
2 (3.9)
|
12 (8.5)
|
21 (36.2)
|
ALT, units/L
|
18.00 (12.00-26.80)
|
19.00 (13.00-28.00)
|
18.00 (11.77-25.25)
|
17.17 (12.75-26.42)
|
ALT >40 units/L
|
30 (12.0)
|
8 (15.7)
|
16 (11.3)
|
6 (10.3)
|
Albumin, g/dL**
|
38.60 (35.70-41.50)
|
39.90 (36.10-42.10)
|
38.80 (36.07-41.56)
|
37.35 (34.28-40.00)
|
eGFR, ml/min/1.73m2 **
|
87.48 (82.03-95.09)
|
93.78 (87.48-101.24)
|
86.96 (81.57-94.64)
|
85.29 (79.27-
90.47)
|
Lg NT pro-BNP**
|
3.05 (2.78-3.35)
|
2.89 (2.70-3.23)
|
3.01 (2.73-3.30)
|
3.25 (2.92-3.52)
|
FIB-4 score***
|
2.27 (1.60-3.17)
|
1.19 (0.94-1.33)
|
2.24 (1.88-2.63)*
|
4.60 (3.83-6.26)
|
Stroke severity on admission
|
GCS
|
14 (9-15)
|
14 (10-15)
|
14 (10-15)
|
10 (7-15)**&
|
NIHSS*
|
8 (3-15)
|
7 (2-13)
|
8 (3-14)
|
13 (4.75-18)
|
NIHSS≥8*
|
125 (49.8)
|
21 (41.2)
|
68 (47.9)
|
36 (62.1)
|
Treatment in hospital
|
Antiplatelet use
|
96 (38.2)
|
18 (35.3)
|
55 (38.7)
|
23 (39.7)
|
Anticoagulant use
|
155 (61.8)
|
33 (64.7)
|
87 (61.3)
|
35 (60.3)
|
Intravenous thrombolysis
|
18 (7.2)
|
4 (7.8)
|
9 (6.3)
|
4 (6.9)
|
Endovascular revascularization
|
42 (16.8)
|
7 (13.7)
|
30 (21.2)
|
5 (8.6)
|
Outcomes at discharge
|
mRS**
|
3 (1-5)
|
2 (1-5)
|
3 (1-5)
|
4.5 (2-5)
|
mRS≥3**
|
117 (46.6)
|
18 (35.3)
|
61 (43.0)
|
38 (65.5)
|
All-cause death
|
25 (10.0)
|
6 (12.0)
|
11 (7.7)
|
8 (13.8)
|
Period of hospitalization days*
|
32 (21-43)
|
32 (21-35)
|
24.5 (21-35)
|
42 (24.75-52)
|
Data are reported as mean ± SD, median (IQR) or number and percentage. † CES, cardioembolic stroke; NVAF, nonvalvular atrial fibrillation; FIB-4, fibrosis-4 score; TIA, transient ischemic attacks; INR, international normalized ratio; AST, aspartate aminotransferase; ALT, alanine aminotransferase; eGFR, estimated glomerular filtration rate; NT-pro BNP, N-terminal Pro-B-type Natriuretic Peptide; NIHSS, National Institutes of Health Stroke Scale; mRS, modified Rankin Scale; ‡ P-values,* for P<0.05, ** for P<0.01, *** for P<0.001. |
Modification Effect of Sex on the Associations Between FIB-4 and Clinical Outcomes of CES Patients Duo to NVAF
When classified by sex, multivariate analysis showed when each point increased in FIB-4, male patients had an increased risk of severe stroke (OR=1.21, 95% CI: 1.10–1.32), major disability (OR=1.82, 95% CI: 1.38-2.40) and 90-days mortality (HR=1.44, 95% CI: 1.20-1.72). When FIB-4 was converted to a categorical variable, compared to no advanced fibrosis likely, there was a significant increased contribution of likely advanced fibrosis to severe stroke (OR=3.12, 95% CI: 1.16-7.11), major disability (OR=13.21, 95% CI: 2.44-55.22), and 90-days mortality (HR=1.20, 95% CI: 1.05-1.74); Indeterminate fibrosis associated with 90-days mortality (HR=1.16, 95% CI: 1.08-1.34), but not for severe stroke and major disability (Table 3, 4, 5).
Whereas the relationships between FIB-4 and severe stroke, major disability and 90-days mortality was not significant in the female group, no matter FIB-4 as a continuous or a categorical variable (Table 3, 4, 5).