Higher High-Mobility Group Box-1 Levels are Associated with White Matter Lesions in Ischemic Stroke Patients

Figures & data

Table 1 Baseline Data of the Study Sample According to the HMGB1 Quartiles

Variables	Serum HMGB1 Levels				P value
	1st Quartile (n = 69)	2nd Quartile (n = 74)	3rd Quartile (n = 71)	4th Quartile (n = 73)
Demographic characteristics
Age, year	65.9 ± 11.3	64.4 ± 11.6	62.8 ± 12.0	66.6 ± 11.6	0.197
Male, n (%)	38 (55.1)	39 (52.7)	39 (54.9)	41 (56.2)	0.980
Body mass index, Kg/m^2	22.8 ± 4.0	23.5 ± 2.7	23.3 ± 4.2	23.2 ± 3.1	0.413
Risk factors, n (%)
Hypertension	44 (63.8)	50 (67.6)	51 (71.8)	56 (76.7)	0.367
Diabetes	21 (30.4)	22 (29.7)	18 (25.4)	24 (32.9)	0.798
Hyperlipidemia	15 (21.7)	9 (12.2)	11 (15.5)	10 (13.7)	0.419
Atrial fibrillation	8 (11.6)	18 (24.3)	12 (16.9)	17 (23.3)	0.182
Coronary heart disease	10 (14.5)	15 (20.3)	6 (8.5)	15 (20.5)	0.155
Current smokers	33 (47.8)	29 (39.2)	23 (32.4)	32 (43.8)	0.279
Clinical data
Pre-treatment of antiplatelet drug, n (%)	20 (29.0)	23 (31.1)	29 (40.8)	25 (34.2)	0.468
Pre-treatment of statin, n (%)	22 (31.9)	19 (25.7)	28 (39.4)	27 (37.0)	0.303
Systolic blood pressure, mmHg	138.2 ± 19.3	132.5 ± 16.7	135.4 ± 17.5	140.0 ± 18.2	0.103
Diastolic blood pressure, mmHg	80.8 ± 10.4	83.7 ± 10.9	80.0 ± 8.5	80.0 ± 9.3	0.112
Baseline NIHSS, score	5.0 (3.0, 7.0)	5.0 (2.0, 7.0)	5.0 (2.0, 8.0)	5.0 (3.0, 8.0)	0.608
WMLs severity, n (%)
Moderate-severe WMLs	25 (36.2)	24 (32.4)	29 (40.8)	51 (69.9)	0.001
Moderate-severe PWMLs	15 (21.7)	14 (18.9)	25 (35.2)	50 (68.5)	0.001
Moderate-severe DWMLs	18 (26.1)	29 (39.2)	26 (36.6)	26 (35.6)	0.382
Stroke subtypes, n (%)					0.105
Large artery atherosclerosis	29 (42.0)	37 (50.0)	32 (45.1)	31 (42.5)
Cardioembolism	7 (10.1)	14 (18.9)	15 (21.1)	17 (23.3)
Small vessel occlusion	24 (34.8)	14 (18.9)	20 (28.2)	23 (31.5)
Others	9 (13.0)	9 (12.2)	4 (5.6)	2 (2.7)
Laboratory data
Total cholesterol, mmol/L	4.0 ± 1.1	4.2 ± 1.2	4.1 ± 1.1	4.0 ± 0.9	0.603
Triglyceride, mmol/L	1.3 (1.0, 1.9)	1.3 (1.0, 1.8)	1.3 (1.0, 1.7)	1.3 (1.0, 1.8)	0.915
High-density lipoprotein, mmol/L	1.0 ± 0.2	1.0 ± 0.2	1.0 ± 0.2	1.1 ± 0.2	0.109
Low-density lipoprotein, mmol/L	2.2 (1.7, 2.9)	2.3 (1.7, 2.9)	2.6 (1.7, 3.0)	2.4 (1.9, 3.0)	0.578
Fasting blood-glucose, mmol/L	7.1 ± 2.8	6.2 ± 1.9	6.7 ± 2.7	6.9 ± 2.9	0.232
Hyper-sensitive C-reactive protein, mg/L	5.0 (1.5, 8.0)	3.0 (1.0, 7.0)	4.0 (1.0, 6.0)	6.0 (3.5, 7.5)	0.008

Abbreviations: NIHSS, National Institutes of Health Stroke Scale; DWMLs, deep white matter lesions; PWMLs, periventricular white matter lesions; WMLs, white matter lesions.

Table 2 Comparison of Baseline Characteristics Stratified by the Status of WMLs

Variables	None-Mild WMLs (n = 158)	Moderate-Severe WMLs (n = 129)	P value
Demographic characteristics
Age, year	63.5 ± 10.4	66.7 ± 12.8	0.017
Male, n (%)	84 (53.2)	73 (56.6)	0.562
Body mass index, Kg/m^2	23.4 ± 3.5	23.2 ± 3.6	0.513
Risk factors, n (%)
Hypertension	103 (65.2)	98 (76.0)	0.047
Diabetes mellitus	38 (24.1)	47 (36.4)	0.022
Hyperlipidemia	28 (17.7)	17 (13.2)	0.292
Atrial fibrillation	35 (22.2)	20 (15.5)	0.155
Coronary heart disease	16 (10.1)	30 (23.3)	0.003
Current smokers	60 (38.0)	57 (44.2)	0.287
Clinical data
Pre-treatment of antiplatelet drug, n (%)	52 (32.9)	45 (34.9)	0.725
Pre-treatment of statin, n (%)	55 (34.8)	41 (31.8)	0.589
Systolic blood pressure, mmHg	135.6 ± 17.6	137.1 ± 18.5	0.489
Diastolic blood pressure, mmHg	81.8 ± 10.3	82.0 ± 9.4	0.491
Baseline NIHSS, score	5.0 (2.0, 7.0)	5.0 (3.0, 8.0)	0.120
Stroke subtypes, n (%)			0.012
Large artery atherosclerosis	60 (38.0)	69 (53.5)
Cardioembolism	27 (17.1)	26 (20.2)
Small vessel occlusion	55 (34.8)	26 (20.2)
Others	16 (10.1)	8 (6.2)
Laboratory data
Total cholesterol, mmol/L	4.1 ± 1.1	4.0 ± 1.1	0.766
Triglyceride, mmol/L	1.3 (1.0, 1.8)	1.3 (1.0, 1.7)	0.447
High-density lipoprotein, mmol/L	1.0 ± 0.2	1.0 ± 0.2	0.513
Low-density lipoprotein, mmol/L	2.3 (1.7, 3.0)	2.4 (1.8, 3.0)	0.689
Fasting blood-glucose, mmol/L	6.5 ± 2.6	7.0 ± 2.5	0.112
Hyper-sensitive C-reactive protein, mg/L	3.9 (1.0, 6.7)	5.6 (3.0, 8.0)	0.007
HMGB1, ng/mL	5.9 (4.2, 10.4)	10.2 (4.7, 14.7)	0.001

Abbreviations: HMGB1, high-mobility group box-1; NIHSS, National Institutes of Health Stroke Scale; WMLs, white matter lesions.

Table 3 Binary Logistic Regression Analysis for the Association Between HMGB1 Levels and WMLs Severity

Variables	Moderate-Severe WMLs		Moderate-Severe PWMLs		Moderate-Severe DWMLs
	OR (95% CI)	P value	OR (95% CI)	P value	OR (95% CI)	P value
Unadjusted model
HMGB1 levels	1.155 (1.095–1.218)	0.001	1.234 (1.163–1.309)	0.001	1.001 (0.925–1.052)	0.975
HMGB1 quartiles
First	Reference		Reference		Reference
Second	0.845 (0.423–1.686)	0.633	0.840 (0.371–1.899)	0.675	1.826 (0.896–3.720)	0.097
Third	1.215 (0.615–2.403)	0.570	1.957 (0.923–4.147)	0.080	1.637 (0.795–3.371)	0.181
Fourth	4.080 (2.025–8.221)	0.001	7.826 (3.676–16.663)	0.001	1.567 (0.763–3.220)	0.221
Model 1
HMGB1 levels	1.154 (1.093–1.218)	0.001	1.233 (1.162–1.308)	0.001	0.998 (0.949–1.049)	0.924
HMGB1 quartiles
First	Reference		Reference		Reference
Second	0.878 (0.436–1.765)	0.715	0.875 (0.384–1.993)	0.750	1.904 (0.929–3.905)	0.079
Third	1.318 (0.660–2.635)	0.434	2.159 (1.005–4.637)	0.049	1.758 (0.846–3.653)	0.130
Fourth	4.093 (2.018–8.302)	0.001	7.982 (3.717–17.141)	0.001	1.550 (0.751–3.196)	0.236
Model 2
HMGB1 levels	1.161 (1.096–1.229)	0.001	1.251 (1.173–1.334)	0.001	0.992 (0.942–1.044)	0.754
HMGB1 quartiles
First	Reference		Reference		Reference
Second	0.918 (0.435–1.937)	0.823	0.899 (0.376–2.150)	0.812	2.407 (0.966–4.341)	0.062
Third	1.755 (0.833–3.698)	0.139	3.168 (1.383–7.255)	0.006	2.059 (0.952–4.454)	0.067
Fourth	4.101 (1.948–8.633)	0.001	9.181 (4.078–20.671)	0.001	1.428 (0.675–3.022)	0.351

Notes: Model 1 adjusted for age and sex; Model 2 adjusted for age, sex, and P value < 0.1 in the univariate analysis.

Abbreviations: CI, confidence interval; HMGB1, high-mobility group box-1; OR, odd ratio.

Figure 1 Receiver operator characteristic curve demonstrated the value of HMGB1 levels for predicting the severity of WMLs.

Abbreviations: DWMLs, deep white matter lesions; HMGB1, high-mobility group box-1; PWMLs, periventricular white matter lesions; WMLs, white matter lesions.