Serum YKL-40 Levels and White Matter Hyperintensities in Patients with Acute Ischemic Stroke

Figures & data

Table 1 Baseline Characteristics of Participants by the Degree of Overall WMH

Variables	All Patients (n = 672)	Overall WMH		P
		None–Mild (n = 337)	Moderate–Severe (n = 335)
Demographic characteristics
Age, years	70 (61, 78)	62 (55, 70)	77 (70, 82)	0.001
Male, n (%)	419 (62.4)	214 (63.5)	205 (61.2)	0.537
Past medical history, n (%)
Hypertension	465 (69.2)	197 (58.5)	268 (80.0)	0.001
Diabetes mellitus	152 (22.6)	79 (23.4)	73 (21.8)	0.609
Lipid metabolism disorders	91 (13.5)	41 (12.2)	50 (14.9)	0.296
Atrial fibrillation	115 (17.1)	51 (15.1)	64 (19.1)	0.172
Coronary artery disease	104 (15.5)	48 (14.2)	56 (16.7)	0.375
Previous stroke or TIA	121 (18.0)	47 (13.9)	74 (22.1)	0.006
Smoking	288 (42.9)	136 (40.4)	152 (45.4)	0.189
Drinking	226 (33.6)	119 (35.3)	107 (31.9)	0.355
Clinical assessment
Systolic blood pressure (mmHg)	150 (136, 163)	146 (130, 165)	150 (139, 164)	0.121
Diastolic blood pressure (mmHg)	87 (80, 96)	87 (80, 98)	87 (79, 96)	0.350
Previous antiplatelet, n (%)	95 (14.1)	45 (13.4)	50 (14.9)	0.559
Previous statin, n (%)	78 (11.6)	39 (11.6)	39 (11.6)	0.978
TOAST subtype				0.002
LAA	306 (45.5)	147 (43.6)	159 (47.5)
CE	130 (19.3)	54 (16.0)	76 (22.7)
SAO	203 (30.2)	115 (34.1)	88 (26.3)
SOE	9 (1.3)	9 (2.7)	0 (0.0)
SUE	24 (3.6)	12 (3.6)	12 (3.6)
Laboratory data
Leukocyte (x10^^9/L)	7.54 (6.14, 9.42)	7.68 (6.14, 9.53)	7.44 (6.16, 9.11)	0.393
TC (mmol/L)	4.64 (3.96, 5.25)	4.70 (4.02, 5.21)	4.58 (3.93, 5.26)	0.463
TG (mmol/L)	1.28 (0.91, 1.78)	1.27 (0.97, 1.85)	1.33 (0.88, 1.74)	0.264
HDL-C (mmol/L)	1.16 (0.99, 1.34)	1.15 (0.96, 1.34)	1.17 (1.01, 1.34)	0.288
LDL-C (mmol/L)	2.52 (2.03, 3.15)	2.46 (2.04, 3.18)	2.57 (2.01, 3.14)	0.992
FBG (mmol/L)	5.80 (5.01, 7.23)	5.67 (4.89, 7.19)	5.90 (5.18, 7.26)	0.014
hs-CRP (mg/L)	3.73 (1.47, 8.51)	3.56 (1.51, 8.62)	3.98 (1.40, 8.52)	0.269
YKL-40 (ng/mL)	134.26 (76.56, 240.17)	134.19 (73.55,238.42)	135.73 (77.24, 242.30)	0.754

Notes: Continuous variables are expressed as medians (IQR), and categorical variables are presented as n (%).

Abbreviations: WMH, white matter hyperintensity; TIA, transient ischemic attack, TOAST, Trial of ORG 10,172 in Acute Stroke Treatment; LAA, large-artery atherosclerosis; CE, cardioembolism; SAO, small-artery occlusion; SOE, stroke of other determined etiology; SUE, stroke of undetermined etiology; TC, total cholesterol; TG, triglyceride; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; FBG, fasting blood glucose; hs-CRP, hyper-sensitive C-reactive protein.

Table 2 Fazekas Scores Among Patients According to Quartiles of YKL-40

Fazekas Score	Serum YKL-40 Levels, ng/mL				P
	First Quartile (23.63–76.51)	Second Quartile (76.56–134.26)	Third Quartile (134.27–239.82)	Fourth Quartile (240.17–798.14)
Overall WMH	2 (1, 4)	3 (1, 4)	2 (1, 4)	3 (2, 4)	0.029
PV-WMH	1 (1, 2)	1 (1, 2)	1 (1, 2)	1 (2, 2)	0.001
D-WMH	1 (0, 2)	1 (1, 2)	1 (0, 2)	1 (0, 2)	0.973

Notes: Fazekas scores are expressed as medians (IQR).

Abbreviations: WMH, white matter hyperintensity; PV-WMH, periventricular white matter hyperintensity; D-WMH, deep white matter hyperintensity.

Table 3 Characteristics of Participants the Degree of PV-WMH and D-WMH

Variables	PV-WMH		P	D-WMH		P
	None–Mild (n = 346)	Moderate–Severe (n = 326)		None–Mild (n = 410)	Moderate–Severe (n = 262)
Demographic characteristics
Age, years	62 (55, 69)	77 (71, 83)	0.001	66 (57, 73)	77 (69, 83)	0.001
Male, n (%)	219 (63.3)	200 (61.3)	0.603	251 (61.2)	168 (64.1)	0.449
Past medical history, n (%)
Hypertension	201 (58.1)	264 (81.0)	0.001	260 (63.4)	203 (78.2)	0.001
Diabetes mellitus	80 (23.1)	72 (22.1)	0.748	94 (22.9)	58 (22.1)	0.811
Lipid metabolism disorders	49 (14.2)	42 (12.9)	0.628	56 (13.7)	35 (13.4)	0.912
Atrial fibrillation	53 (15.3)	62 (19.0)	0.203	63 (15.4)	52 (19.8)	0.132
Coronary artery disease	47 (13.6)	57 (17.5)	0.162	60 (14.6)	44 (16.8)	0.450
Previous stroke or TIA	44 (12.7)	77 (23.6)	0.001	62 (15.1)	59 (22.5)	0.015
Smoking	144 (41.6)	144 (44.2)	0.504	163 (39.8)	125 (47.7)	0.042
Drinking	128 (37.0)	98 (30.1)	0.057	136 (33.2)	90 (34.4)	0.752
Clinical assessment
Systolic blood pressure (mmHg)	150 (134, 162)	147 (137, 164)	0.757	150 (135, 164)	148 (137, 163)	0.594
Diastolic blood pressure (mmHg)	87 (80, 99)	88 (79, 96)	0.273	87 (80, 96)	88 (79, 96)	0.807
Previous antiplatelet, n (%)	42 (12.1)	53 (16.3)	0.126	59 (14.4)	36 (13.7)	0.814
Previous statin, n (%)	37 (10.7)	41 (12.6)	0.446	50 (12.2)	28 (10.7)	0.552
TOAST subtype			0.001			0.042
LAA	145 (41.9)	161 (49.4)		180 (43.9)	126 (48.1)
CE	54 (15.6)	76 (23.3)		74 (18.0)	56 (21.4)
SAO	125 (36.1)	78 (23.9)		134 (32.7)	69 (26.3)
SOE	8 (2.3)	1 (0.3)		9 (2.2)	0 (0.0)
SUE	14 (4.0)	10 (3.1)		13 (3.2)	11 (4.2)
Laboratory data
Leukocyte (x10^^9/L)	7.52 (6.05, 9.32)	7.56 (6.42, 9.61)	0.243	7.55 (6.17, 9.45)	7.51 (6.09, 9.39)	0.967
TC (mmol/L)	4.70 (4.04, 5.21)	4.57 (3.91, 5.28)	0.259	4.69 (4.03, 5.21)	4.53 (3.90, 5.31)	0.364
TG (mmol/L)	1.28 (0.97, 1.88)	1.28 (0.86, 1.74)	0.037	1.23 (0.93, 1.79)	1.36 (0.88, 1.77)	0.945
HDL-C (mmol/L)	1.16 (0.95, 1.34)	1.17 (1.02, 1.34)	0.228	1.16 (0.99, 1.34)	1.16 (1.00, 1.34)	0.637
LDL-C (mmol/L)	2.48 (2.00, 3.16)	2.57 (2.04, 3.14)	0.857	2.50 (2.03, 3.19)	2.57 (2.03, 3.11)	0.909
FBG (mmol/L)	5.64 (4.89, 7.17)	6.07 (5.21, 7.33)	0.004	5.70 (4.95, 7.26)	5.91 (5.19, 7.20)	0.025
hs-CRP (mg/L)	3.49 (1.49, 8.12)	4.28 (1.40, 9.02)	0.033	3.57 (1.51, 8.49)	3.98 (1.33, 8.55)	0.265
YKL-40 (ng/mL)	130.94 (63.53, 232.33)	150.21 (81.13, 261.60)	0.007	134.61 (78.49, 239.94)	130.83 (76.26, 241.12)	0.228

Notes: Continuous variables are expressed as medians (IQR), and categorical variables are presented as n (%).

Abbreviations: PV-WMH, periventricular white matter hyperintensity; D-WMH, deep white matter hyperintensity; TIA, transient ischemic attack, TOAST, Trial of ORG 10,172 in Acute Stroke Treatment; LAA, large-artery atherosclerosis; CE, cardioembolism; SAO, small-artery occlusion; SOE, stroke of other determined etiology; SUE, stroke of undetermined etiology; TC, total cholesterol; TG, triglyceride; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; FBG, fasting blood glucose; hs-CRP, hyper-sensitive C-reactive protein.

Table 4 Logistic Regression Analyses of YKL-40 with White Matter Hyperintensity

YKL-40	Overall WMH		PV-WMH		D-WMH
	OR (95% CI)	P	OR (95% CI)	P	OR (95% CI)	P
Unadjusted model
First quartile	Reference		Reference		Reference
Second quartile	1.154 (0.752–1.770)	0.513	1.273 (0.827–1.958)	0.273	0.975 (0.630–1.510)	0.911
Third quartile	1.024 (0.667–1.571)	0.913	0.976 (0.632–1.506)	0.912	0.904 (0.583–1.403)	0.654
Fourth quartile	1.210 (0.789–1.857)	0.383	2.456 (1.583–3.810)	0.001	0.975 (0.630–1.510)	0.911
Age- and sex-adjusted
First quartile	Reference		Reference		Reference
Second quartile	1.150 (0.673–1.964)	0.610	1.385 (0.786–2.440)	0.260	0.933 (0.565–1.540)	0.785
Third quartile	1.217 (0.714–2.075)	0.469	1.189 (0.678–2.086)	0.545	1.025 (0.620–1.695)	0.924
Fourth quartile	0.790 (0.458–1.362)	0.396	2.595 (1.434–4.697)	0.002	0.699 (0.421–1.162)	0.167
Multivariable adjusted*
First quartile	Reference		Reference		Reference
Second quartile	1.124 (0.649–1.945)	0.677	1.318 (0.733–2.369)	0.356	0.897 (0.539–1.493)	0.676
Third quartile	1.171 (0.679–2.021)	0.570	1.107 (0.614–1.995)	0.736	1.052 (0.631–1.752)	0.847
Fourth quartile	0.762 (0.434–1.336)	0.343	2.473 (1.316–4.646)	0.005	0.695 (0.413–1.171)	0.172

Notes: *Overall WMH: adjusted for age, gender, hypertension, previous stroke, TOAST subtype, and FBG. PV-WMH: adjusted for age, gender, hypertension, previous stroke, drinking, TOAST subtype, TG, FBG, and Hs-CRP. D-WMH: adjusted for age, gender, hypertension, previous stroke or TIA, smoking, TOAST subtype, and FBG.

Abbreviations: WMH, white matter hyperintensity; PV-WMH, periventricular white matter hyperintensity; D-WMH, deep white matter hyperintensity; OR, odds ratio; CI, confidence interval.

Figure 1 Serum YKL-40 levels in different groups according to (A) overall WMH, (B) PV-WMH and (C) D-WMH in AIS patients. Horizontal lines represent medians (IQR).

Abbreviations: WMH, white matter hyperintensity; PV-WMH, periventricular white matter hyperintensity; D-WMH, deep white matter hyperintensity.