A total of 2302 patients with acute ischemic stroke within 7-day of onset were screened, and 126 patients were excluded because of the absence of neuroimaging evidence, or poor neuroimaging quality, or diffusion-weighed image negative stroke. Among the remaining 2176 patients, 548 patients were diagnosed with cardioembolism, 310 patients with stroke of undetermined etiology and 96 patients with stroke of other determined etiology. These patients were also excluded. Of the remaining 1222 patients, 412 were excluded because of a SSI without an atherosclerotic stenosis on the parental artery. Then, 810 patients were with a definite diagnosis of atherosclerotic stroke. Of these patients, 85 accepted intravenous thrombolysis and (or) endovascular thrombectomy and 37 had a prestroke mRS > 2 points. After the exclusion of these patients, 688 participants were ultimately enrolled in this study (Figure 2).
Figure 2. Flow chart of the participants selection.
Abbreviations: DWI indicates diffusion weighed image; mRS, modified Ranking Scale; NIHSS, National Institute of Health Stroke Scale.
The baseline data of all participants
The median age was 69.0 (61.0, 76.0) years, and 245 (35.6%) participants were female. The median of NIHSS score on admission was 2.0 (1.0, 4.0) points. Of all participants, 229 (33.3%) were diagnosed with MSI, 244 (35.5%) with SSI, 135 (19.6%) with large infarct and 80 (11.6%) with BZI. 154 (22.4%) participants experienced ND during hospitalization, and 184 (26.7%) participants suffered poor clinical outcomes at discharge (Table 1).
Table 1 Baseline data of all participants.
Clinical characteristics
|
All participants
(n=688)
|
Female, n (%)
|
245 (35.6)
|
Age (year), median (IQR)
|
69.0 (61.0, 76.0)
|
Hypertension, n (%)
|
532 (77.3)
|
Diabetes mellitus, n (%)
|
252 (36.6)
|
Smoking, n (%)
|
281 (40.8)
|
Alcohol consumption, n (%)
|
223 (32.4)
|
Previous stroke, n (%)
|
165 (24.0)
|
Time of onset (hour), median (IQR)
|
24.0 (10.0, 72.0)
|
BMI, median (IQR)
|
24.58 (22.49, 27.34)
|
SBP (mmHg), mean ± SD
|
156.3 ± 23.5
|
DBP (mmHg), median (IQR)
|
82.0 (75.0, 92.0)
|
TG (mmol/L), median (IQR)
|
1.45 (1.04, 2.00)
|
TC (mmol/L), median (IQR)
|
4.64 (3.87, 5.32)
|
HDL-C (mmol/L), median (IQR)
|
1.02 (0.85, 1.25)
|
LDL-C (mmol/L), median (IQR)
|
2.66 (2.06, 3.28)
|
HbA1c (%), median (IQR)
|
6.30 (5.80, 8.08)
|
Homocysteine (mmol/L), median (IQR)
|
12.23 (9.44, 15.60)
|
Neutrophil count (×109/L), median (IQR)
|
4.80 (3.70, 6.20)
|
Hs-CRP (mg/L), median (IQR)
|
1.65 (0.50, 5.88)
|
NLR, median (IQR)
|
2.92 (2.05, 4.28)
|
Initial NIHSS (point), median (IQR)
|
2.0 (1.0, 4.0)
|
Stroke mechanism
|
|
MSI, n (%)
|
229 (33.3)
|
SSI, n (%)
|
244 (35.5)
|
Large infarct, n (%)
|
135 (19.6)
|
BZI, n (%)
|
80 (11.6)
|
ND, n (%)
|
154 (22.4)
|
Posterior lesion, n (%)
|
123 (17.9)
|
Poor outcome at discharge, n (%)
|
184 (26.7)
|
Abbreviations: BMI indicates body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; TG, triglyceride; TC, total cholesterol; LDL-C, low-density lipoprotein cholesterol; HbA1c, glycosylated hemoglobin; hs-CRP, high-sensitivity C-reactive protein; NLR, neutrophil to lymphocyte ratio; NIHSS, National Institutes of Health Stroke Scale; MSI, multiple small infarcts; SSI, single subcortical infarct; BZI, borderzone infarct; ND, neurological deterioration.
The comparisons of baseline data among 4 subgroups
All participants were classified into 4 groups according to the stroke pattern: MSI (n=229), SSI (n=244), large infarct (n = 135) and BZI (n=80) groups. Among the 4 groups, the systolic blood pressure on admission (p = 0.011), the proportion of female (p = 0.041), levels of homocysteine (p < 0.001), neutrophil count (p = 0.001), neutrophil to lymphocyte ratio (NLR) (p < 0.001), the proportion of posterior lesion (p < 0.001) and initial NIHSS (p = 0.032) were significantly different. The incidence of ND in group of BZI was higher than in other 3 groups [41.3% vs. 13.5% (MSI), 23.8% (SSI) and 23.7% (large infarct), p < 0.001], and large infarct and BZI groups had higher proportions of poor outcome than other 2 groups [39.3% (large infarct) and 37.5% (BZI) vs. 16.2% (MSI) and 26.2% (SSI), p < 0.001] (Table 2).
Table 2 Univariable analyses of baseline data among patients with different stroke mechanisms.
Clinical characteristics
|
MSI
(n=229)
|
SSI
(n=244)
|
Large infarct
(n=135)
|
BZI
(n=80)
|
P-value
|
Female, n (%)
|
69 (30.1)
|
102 (41.8)
|
43 (31.9)
|
31 (38.8)
|
0.041*
|
Age (year), median (IQR)
|
69.0 (60.0, 76.0)
|
69.0 (63.0, 76.0)
|
68.0 (61.0, 77.0)
|
69.0 (59.0, 75.8)
|
0.57
|
Hypertension, n (%)
|
173 (75.5)
|
191 (78.3)
|
105 (77.8)
|
63 (78.8)
|
0.89
|
Diabetes mellitus, n (%)
|
80 (34.9)
|
96 (39.3)
|
51 (37.8)
|
35 (31.3)
|
0.55
|
Smoking, n (%)
|
99 (43.2)
|
92 (37.7)
|
61 (45.2)
|
29 (36.3)
|
0.35
|
Alcohol consumption, n (%)
|
85 (37.1)
|
71 (29.1)
|
42 (31.1)
|
25 (31.3)
|
0.30
|
Previous stroke, n (%)
|
56 (24.5)
|
63 (25.8)
|
30 (22.2)
|
16 (20.0)
|
0.70
|
Time of onset (hour),
median (IQR)
|
24.0 (8.8, 72.0)
|
24.0 (10.3, 48.0)
|
24.0 (7.0, 48.0)
|
24.0 (20.5, 96.0)
|
0.054
|
BMI, median (IQR)
|
24.60 (22.97, 27.34)
|
24.91 (23.14, 27.34)
|
24.22 (22.23, 27.34)
|
23.91 (22.22, 27.34)
|
0.37
|
SBP (mmHg), median (IQR)
|
153.9 ± 22.1
|
158.0 ± 23.4
|
159.1 ± 22.6
|
153.1 ± 28.1
|
0.07
|
DBP (mmHg), median (IQR)
|
80.0 (74.0, 90.0)
|
83.5 (75.0,. 94.0)
|
83.0 (75.0, 92.0)
|
80.0 (71.5, 91.8)
|
0.12
|
TG (mmol/L), median (IQR)
|
1.48 (1.04, 2.09)
|
1.48 (1.08, 2.21)
|
1.38 (1.07, 1.73)
|
1.36 (0.97, 1.89)
|
0.085
|
TC (mmol/L), median (IQR)
|
4.67 (3.82, 5.36)
|
4.62 (3.95, 5.36)
|
4.61 (3.93, 5.42)
|
4.69 (3.45, 5.19)
|
0.84
|
HDL-C (mmol/L), median (IQR)
|
1.02 (0.85, 1.26)
|
1.02 (0.85, 1.26)
|
1.04 (0.86, 1.34)
|
0.99 (0.84, 1.20)
|
0.60
|
LDL-C (mmol/L), median (IQR)
|
2.65 (2.05, 3.25)
|
2.68 (2.11, 3.32)
|
2.65 (2.06, 3.38)
|
2.64 (7.18, 3.15)
|
0.85
|
HbA1c (%), median (IQR)
|
6.20 (5.70, 7.80)
|
6.65 (5.90, 8.50)
|
6.50 (5.80, 8.10)
|
6.20 (5.90, 7.58)
|
0.05
|
Homocysteine (mmol/L),
median (IQR)
|
12.45 (9.74, 15.59)
|
11.45 (8.78, 14.27)
|
13.56 (10.28, 17.46)
|
12.35 (9.85, 16.92)
|
< 0.001*
|
Neutrophil count (×109/L),
median (IQR)
|
4.50 (3.60, 5.90)
|
4.63 (3.53, 5.90)
|
5.40 (3.90, 7.00)
|
5.00 (4.10, 6.68)
|
0.001*
|
Hs-CRP (mg/L), median (IQR)
|
1.60 (0.50, 5.55)
|
1.50 (0.50, 5.38)
|
2.10 (0.50, 6.00)
|
1.70 (0.50, 7.24)
|
0.72
|
NLR, median (IQR)
|
2.64 (1.89, 4.06)
|
2.71 (1.93, 3.91)
|
3.36 (2.53, 4.94)
|
3.35 (2.28, 5.04)
|
< 0.001*
|
Initial NIHSS (point),
median (IQR)
|
2.0 (1.0, 3.0)
|
2.0 (1.0, 4.0)
|
2.0 (1.0, 7.0)
|
2.0 (1.0, 4.0)
|
0.032*
|
Posterior lesion, n (%)
|
32 (14.0)
|
53 (21.7)
|
35 (25.9)
|
3 (3.8)
|
< 0.001*
|
ND, n (%)
|
31 (13.5)
|
58 (23.8)
|
32 (23.7)
|
33 (41.3)
|
< 0.001*
|
Poor outcome at discharge, n (%)
|
37 (16.2)
|
64 (26.2)
|
53 (39.3)
|
30 (37.5)
|
< 0.001*
|
Abbreviations: MSI indicates multiple small infarcts; SSI, single subcortical infarct; BZI, borderzone infarct; BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; TG, triglyceride; TC, total cholesterol; LDL-C, low-density lipoprotein cholesterol; HbA1c, glycosylated hemoglobin; hs-CRP, high-sensitivity C-reactive protein; NLR, neutrophil to lymphocyte ratio; NIHSS, National Institutes of Health Stroke Scale; ND, neurological deterioration.
* p < 0.05 was considered statistically significant.
The comparisons of the risk of ND in the multivariable analyses
Due to the lowest incidences of ND and poor outcome in MSI group (13.5% and 16.2%, respectively), this group was used as a reference in the multivariable analyses. After adjusting for age, stroke pattern and clinical factors with a p < 0.1 in the univariable analyses, including sex, time of onset, systolic blood pressure on admission, triglyceride, glycosylated hemoglobin, homocysteine, neutrophil count, NLR, initial NIHSS and the proportion of posterior lesion, the BZI group had the highest incidence of ND (OR= 4.33, 95% CI = 2.37–7.94, p < 0.001) by comparing to the MSI group, followed by SSI (OR= 1.94, 95% CI = 1.18–3.17, p = 0.009) and large infarct groups (OR= 1.83, 95% CI = 1.03–3.24, p = 0.038). (Table 3).
Table 3 The correlations of stroke mechanisms with neurological deterioration.
Stroke mechanisms
|
Neurological deterioration
|
Crude OR (95%CI)
|
P-value
|
Adjusted OR§ (95%CI)
|
P-value
|
MSI
|
Ref.
|
|
Ref.
|
|
SSI
|
1.99 (1.23–3.22)
|
0.005*
|
1.94 (1.18–3.17)
|
0.009*
|
Large infarct
|
1.98 (1.15–3.43)
|
0.014*
|
1.83 (1.03–3.24)
|
0.038*
|
BZI
|
4.49 (2.50–8.04)
|
< 0.001*
|
4.33 (2.37–7.94)
|
< 0.001*
|
§ Adjusted for age, sex, time of onset, systolic blood pressure on admission, triglyceride, glycosylated hemoglobin, homocysteine, neutrophil count, neutrophil to lymphocyte ratio, initial NIHSS and posterior lesion.
Abbreviations: MSI indicates multiple small infarcts; SSI, single subcortical infarct; BZI, borderzone infarct.
* p < 0.05 was considered statistically significant.
The comparisons of the risk of poor outcome in the multivariable analyses
MSI group was still used as reference. In the logistic regression model, after adjusting for forementioned confounders other than initial NIHSS, compared to MIS group, BZI group (OR= 3.13, 95% CI = 1.70–5.78, p < 0.001) and large infarct group (OR= 3.04, 95% CI = 1.79–5.16, p < 0.001) both had an approximate 2-fold increased risk of poor outcome, whereas SSI group (OR= 1.79, 95% CI = 1.11–2.89, p = 0.017) had a less than 1-fold increased risk. After including initial NIHSS into the model, compared to MIS group, BZI group had an approximate 3-fold increased risk of poor outcome (OR= 4.16, 95% CI = 2.04–8.50, p < 0.001), and large infarct group had only a 1.6-fold increased risk (OR= 2.60, 95% CI = 1.33–5.08, p = 0.005) (Table 4).
Table 4 The correlations of stroke mechanisms with poor outcome at discharge.
Stroke mechanisms
|
Poor outcome at discharge
|
Model 1
|
Model 2
|
Adjusted OR§ (95%CI)
|
P-value
|
Adjusted OR†(95%CI)
|
P-value
|
MSI
|
Ref.
|
|
Ref.
|
|
SSI
|
1.79 (1.11–2.89)
|
0.017*
|
1.87 (1.06–3.32)
|
0.032*
|
Large infarct
|
3.04 (1.79–5.16)
|
< 0.001*
|
2.60 (1.33–5.08)
|
0.005*
|
BZI
|
3.13 (1.70–5.78)
|
< 0.001*
|
4.16 (2.04–8.50)
|
< 0.001*
|
§ Adjusted for age, sex, time of onset, systolic blood pressure on admission, triglyceride, glycosylated hemoglobin, homocysteine, neutrophil count, neutrophil to lymphocyte ratio and posterior lesion.
† Adjusted for confounders included into model 1 plus initial NIHSS.
Abbreviations: MSI indicates multiple small infarcts; SSI, single subcortical infarct; BZI, borderzone infarct, NIHSS, National Institutes of Health Stroke Scale.
* p < 0.05 was considered statistically significant.
The proportions of various stroke severity among different stroke patterns
Among the 4 groups, the proportion of moderate-severe stroke was the lowest in MSI group (14.4%), followed by BZI (20.0%) and SSI (20.5%) groups. Large infarct group had the highest proportion of participants with moderate-severe stroke (31.9%) (Figure 3).
Figure 3. The distribution of various stroke severity levels in four stroke patterns.
Abbreviations: MSI indicates multiple small infarcts; SSI, single subcortical infarct; BZI, borderzone infarct.
The comparisons of NLR among different stroke patterns
The NLR of BZI and large infarct groups were higher than that of other 2 groups [3.35 (2.28, 5.04) (BZI) and 3.36 (2.53, 4.94) (large infarct) vs. 2.64 (1.89, 4.06) (MSI) and 2.71 (1.93, 3.91) (SSI), p < 0.001]. In the pairwise comparisons, the NLR in large infarct group was higher than in MSI and SSI groups [3.36 (2.53, 4.94) vs. 2.64 (1.89, 4.06), p = 0.001; 3.36 (2.53, 4.94) vs. 2.71 (1.93, 3.91), p = 0.001], respectively. In BZI group, the NLR was significantly higher than in MSI group [3.35 (2.28, 5.04) vs. 2.64 (1.89, 4.06), p = 0.046], and was marginal significantly higher than in SSI group [3.35 (2.28, 5.04) vs. 2.71 (1.93, 3.91), p = 0.053] (Figure 4).
Figure 4. Comparisons of NLR between different atherosclerotic stroke patterns.
* p < 0.05; ** p < 0.01.
p < 0.05 was considered statistically significant.
Abbreviations: MSI indicates multiple small infarcts; SSI, single subcortical infarct; BZI, borderzone infarct; NLR, neutrophil to lymphocyte ratio.