Eosinophil-to-Monocyte Ratio is a Potential Predictor of Prognosis in Acute Ischemic Stroke Patients After Intravenous Thrombolysis

Figures & data

Figure 1 Flow diagram showing the patient selection process.

Table 1 Demographic and Laboratory Characteristics of AIS Patients and Healthy Controls

Variables	After Propensity Score Matching
	AIS (n = 130)	HCs (n = 130)	p value
Age (years)	57.50 (51.00–65.00)	58.00 (51.75–65.00)	0.967
Sex (male, n.%)	93 (71.5)	92 (70.7)	0.891
EMR	0.16 (0.06–0.27)	0.27 (0.17–0.47)	< 0.001

Abbreviations: AIS, acute ischemic stroke; HCs, healthy controls; EMR, eosinophil to monocyte ratio.

Table 2 Characteristics of AIS Patients According to EMR Tertiles

Variable	Total (n = 280)	EMR < 0.09 (n = 96)	0.09 ≤ EMR ≤ 0.21 (n = 92)	EMR > 0.21 (n = 92)	p value
Demographic data
Age (years)	69.00 (59.00–77.00)	66.00 (60.00–79.75)	70.00 (57.25–76.00)	70.00 (58.25–77.75)	0.936
Sex (male, n.%)	179 (63.90)	55 (57.20)	62 (67.30)	62 (67.30)	0.248
Stroke risk factors (n.%)
Hypertension (n.%)	172 (61.40)	58 (60.40)	58 (63.00)	56 (60.80)	0.945
Diabetes (n.%)	55 (19.60)	15 (15.60)	18 (19.50)	22 (23.90)	0.377
Hyperlipidemia (n.%)	32 (11.40)	10 (10.40)	13 (14.10)	9 (9.70)	0.604
Atrial fibrillation (n.%)	66 (23.50)	31 (32.20)	21 (22.80)	14 (15.20)	0.022
DNT (min)	62.56 ± 27.51	67.94 ± 31.01	58.53 ± 22.87	60.92 ± 27.24	0.051
ONT (min)	161.96 ± 50.18	167.50 ± 50.48	157.51 ± 46.95	160.64 ± 52.95	0.377
Infarct volume (mL)	4.44 (1.37–20.48)	15.04 (2.08–46.66)	7.99 (1.19–20.91)	2.24 (0.50–8.01)	< 0.001
ASPECT	10 (9–10)	9.5 (9–10)	10 (9–10)	10 (10–10)	< 0.001
sICH	6 (2.14)	4 (4.17)	1 (1.09)	1 (1.09)	0.534
TOAST subtype (n.%)
Cardioembolism (n.%)	94 (33.57)	45 (46.88)	25 (27.17)	24 (26.09)	0.047
Large artery atherosclerosis (n.%)	113 (40.36)	32 (33.33)	39 (42.39)	42 (45.65)
Small vessel occlusion (n.%)	40 (14.29)	9 (9.38)	15 (16.30)	16 (17.39)
Other or undetermined (n.%)	33 (11.79)	10 (10.42)	13 (14.13)	10 (10.87)
Laboratory data on 24 hours admission
WBC (×10^9/L)	7.40 (6.10–8.80)	8.35 (7.30–10.78)	7.25 (5.83–8.58)	6.60 (5.70–7.70)	< 0.001
NLR	3.23 (2.20–5.00)	5.26 (3.76–8.29)	2.81 (2.07–3.93)	2.56 (1.89–3.44)	< 0.001
PLR	125.80 (96.16–169.35)	153.25 (116.20–199.04)	112.27 (87.92–154.58)	116.75 (86.88–152.98)	< 0.001
UA (μmol/L)	326.66 ± 85.34	321.67 ± 88.60	337.23 ± 82.91	321.03 ± 84.49	0.368
Urea	4.83 (4.03–6.00)	4.90 (4.17–6.24)	5.11 (4.20–6.00)	4.58 (3.80–5.64)	0.118
Creatinine	68.00 (61.25–76.00)	68.00 (61.00–75.25)	68.00 (62.00–78.00)	68.00 (61.00–75.00)	0.860
TC	1.24 (0.94–1.65)	1.13 (0.86–1.66)	1.27 (0.95–1.76)	1.32 (0.99–1.65)	0.232
HDL-C (mmol/L)	1.07 (0.93–1.29)	1.09 (0.93–1.32)	1.08 (0.95–1.30)	1.04 (0.92–1.23)	0.498
Apo-A1 (g/L)	1.28 (1.15–1.44)	1.29 (1.15–1.46)	1.27 (1.14–1.48)	1.29 (1.18–1.39)	0.931

Abbreviations: AIS, acute ischemic stroke; DNT, door to needle time; ONT, onset to needle time; ASPECT, Alberta Stroke Program Early CT Score; sICH, symptomatic intracranial hemorrhage; TOAST, Trial of Org 10,172 in Acute Stroke Treatment; EMR, eosinophil to monocyte ratio; WBC, white blood cell count; NLR, neutrophil to lymphocyte ratio; PLR, platelet to lymphocyte ratio; UA, uric acid; TC, triglyceride; HDL-C, high density lipoprotein-cholesterol; Apo-A1, apolipoprotein-A1.

Table 3 Comparison of Clinical Characteristics Between Good and Poor Outcome (or Alive and Dead)

	Good Outcome (n = 194)	Poor Outcome (n = 86)	p value	Alive (n = 253)	Dead (n = 27)	p value
Demographic data
Age (years)	66.00 (56.00–75.00)	75.00 (64.00–82.0)	< 0.001	68.00 (57.50–76.00)	81.00 (72.00–85.00)	< 0.001
Sex (male, n.%)	129 (66.40)	50 (58.10)	0.179	165 (65.20)	14 (51.80)	0.169
Stroke risk factors (n.%)
Hypertension	115 (59.20)	57 (66.20)	0.219	156 (61.60)	16 (59.20)	0.990
Diabetes	40 (20.60)	15 (17.40)	0.566	53 (20.90)	2 (7.40)	0.106
Hyperlipidemia	18 (9.20)	14 (16.20)	0.089	30 (11.80)	2 (7.40)	0.751
Atrial fibrillation	35 (18.00)	31 (36.00)	0.001	53 (20.90)	13 (48.10)	0.002
DNT (min)	62.94 ± 29.34	61.69 ± 23.02	0.725	62.53 ± 28.29	62.81 ± 19.14	0.959
ONT (min)	161.19 ± 51.09	163.72 ± 48.34	0.697	160.64 ± 50.54	174.33 ± 45.73	0.178
Infarct volume (mL)	2.68 (0.92–12.65)	21.51 (3.99–66.79)	< 0.001	4.11 (1.26–17.92)	63.50 (28.82–131.47)	0.001
ASPECT	10 (9–10)	9 (8–10)	< 0.001	10 (9–10)	9 (8–10)	0.001
sICH	0	6 (7.00)	0.001	2 (0.79)	4 (14.81)	0.001
Evaluation of stroke
NIHSS on admission	6 (4.00–9.00)	13 (8.00–18.50)	< 0.001	6 (4–10)	18 (13.00–21.00)	< 0.001
3-month mRS	1 (0–1)	4 (3–6)	< 0.001	1 (0–2)	6 (6)	< 0.001
TOAST subtype (n.%)
Cardioembolism	48 (24.74)	46 (53.49)	< 0.001	72 (28.46)	22 (81.48)	< 0.001
Large artery atherosclerosis	83 (42.78)	30 (34.88)		110 (43.48)	3 (11.11)
Small vessel occlusion	40 (20.62)	0		40 (15.81)	0
Other or undetermined	23 (11.86)	10 (11.63)		31 (12.25)	2 (7.41)
Laboratory data on 24 hours admission
WBC (×10^9/L)	7.10 (5.70–8.20)	8.55 (7.20–10.63)	< 0.001	7.30 (6.00–8.70)	8.70 (7.30–11.50)	0.004
Eosinophil (×10^9/L)	0.09 (0.04–0.15)	0.03 (0.01–0.08)	< 0.001	0.08 (0.03–0.14)	0.01 (0.00–0.02)	< 0.001
Monocyte (×10^9/L)	0.52 ± 0.25	0.50 ± 0.21	0.597	0.50 (0.40–0.60)	0.40 (0.30–0.60)	0.021
Platelet count (×10^9/L)	196.49 ± 54.02	190.88 ± 58.85	0.437	197.68 ± 55.09	167.48 ± 52.69	0.007
UA (μmol/L)	330.82 ± 81.51	315.59 ± 94.50	0.200	324.44 ± 82.89	354.89 ± 110.82	0.134
Urea	4.70 (3.96–5.63)	5.60 (4.27–6.30)	0.001	4.79 (4.03–5.94)	5.49 (4.12–6.37)	0.197
Creatinine	68.00 (60.50–75.50)	68.00 (63.00–78.00)	0.327	68.00 (62.00–76.00)	68.00 (61.00–88.00)	0.418
TC	1.29 (0.96–1.65)	1.16 (0.90–1.67)	0.232	1.24 (0.94–1.65)	1.29 (0.99–1.86)	0.661
HDL-C (mmol/L)	1.07 (0.95–1.28)	1.07 (0.91–1.33)	0.921	1.07 (0.94–1.29)	1.02 (0.81–1.32)	0.237
Apo-A1 (g/L)	1.30 (1.17–1.43)	1.23 (1.12–1.48)	0.282	1.28 (1.15–1.44)	1.25 (1.02–1.47)	0.498
EMR	0.18 (0.10–0.29)	0.05 (0.02–0.15)	< 0.001	0.16 (0.08–0.28)	0.02 (0.00–0.04)	< 0.001
NLR	2.77 (2.04–3.96)	4.44 (3.49–7.80)	< 0.001	3.00 (2.15–4.42)	6.38 (4.00–11.00)	< 0.001
PLR	121.30 (91.59–162.93)	143.46 (106.41–192.04)	0.011	125.00 (94.15–164.59)	153.64 (100.00–242.86)	0.042

Abbreviations: AIS, acute ischemic stroke; DNT, door to needle time; ONT, onset to needle time; ASPECT, Alberta Stroke Program Early CT Score; sICH, symptomatic intracranial hemorrhage; TOAST, Trial of Org 10,172 in Acute Stroke Treatment; NIHSS, national institute of health stroke scale; mRS, modified Rankin Scale; WBC, white blood cell count; UA, uric acid; TC, triglyceride; HDL-C, high density lipoprotein-cholesterol; Apo-A1, apolipoprotein-A1; EMR, eosinophil to monocyte ratio; NLR, neutrophil to lymphocyte ratio; PLR, platelet to lymphocyte ratio.

Figure 2 (A) Distribution of NIHSS on admission in the tertiles of increasing EMR levels. (B) Distribution of 3-month mRS scores in the tertiles of increasing EMR levels.

Table 4 Univariate Logistic Regression Analyses for Prognosis

Variables	Univariate Logistic Regression
	Poor Outcome OR (95% CI)	p value	Dead OR (95% CI)	p value
Age (years)	1.057 (1.032–1.083)	< 0.001	1.080 (1.036–1.126)	< 0.001
Sex (male, n.%)	0.700 (0.415–1.179)	0.180	0.574 (0.259–1.276)	0.173
Hypertension (n.%)	1.398 (0.819–2.389)	0.220	0.995 (0.434–2.281)	0.990
Diabetes (n.%)	0.825 (0.428–1.592)	0.566	0.314 (0.072–1.373)	0.124
Hyperlipidemia (n.%)	1.901 (0.898–4.026)	0.093	0.595 (0.134–2.638)	0.494
Atrial fibrillation (n.%)	2.561 (1.445–4.539)	0.001	3.504 (1.554–7.903)	0.003
WBC (×10^9/L)	1.377 (1.220–1.554)	< 0.001	1.290 (1.111–1.499)	0.001
UA (μmol/L)	0.998 (0.995–1.001)	0.200	1.004 (0.999–1.009)	0.136
Urea	1.114 (0.990–1.255)	0.073	1.103 (0.993–1.226)	0.068
Creatinine	1.001 (0.998–1.005)	0.518	1.003 (0.999–1.007)	0.112
TC	0.841 (0.620–1.139)	0.263	0.952 (0.610–1.485)	0.828
HDL-C (mmol/L)	1.098 (0.393–3.063)	0.859	0.304 (0.044–2.087)	0.226
Apo-A1 (g/L)	0.689 (0.214–2.220)	0.532	0.324 (0.035–2.977)	0.320
EMR^†	0.970 (0.953–0.988)	0.001	0.821 (0.750–0.898)	< 0.001

Abbreviations: WBC, white blood cell count; UA, uric acid; TC, triglyceride; HDL-C, high density lipoprotein-cholesterol; Apo-A1, apolipoprotein-A1; EMR, eosinophil to monocyte ratio; ^†OR is intended for per 0.01-point increase of EMR.

Table 5 Adjusted Models for Prognosis at 3 Months

Variables	Multiple Logistic Regression
	Poor Outcome OR (95% CI)	p value	Dead OR (95% CI)	p value
Model 1
T1	1		1
T2	0.230 (0.121–0.438)	< 0.001	0.031 (0.004–0.236)	0.001
T3	0.186 (0.095–0.364)	< 0.001	0.031 (0.004–0.236)	0.001
Model 2
T1	1		1
T2	0.197 (0.099–0.394)	< 0.001	0.027 (0.003–0.210)	0.001
T3	0.153 (0.074–0.314)	< 0.001	0.027 (0.003–0.206)	0.001
Model 3
T1	1		1
T2	0.295 (0.142–0.610)	0.001	0.034 (0.004–0.272)	0.001
T3	0.270 (0.124–0.589)	0.001	0.036 (0.004–0.292)	0.002

Notes: Model 1 is univariate analysis. Model 2 is adjusted for age. Model 3 for poor outcome is adjusted for age, atrial fibrillation and white blood cell count. Model 3 for death is adjusted for age, atrial fibrillation and white blood cell count.

Table 6 Diagnostic Values of the EMR, NLR, PLR and NLR + EMR for Stroke Outcome

	AUC (95% CI)	p	p*	Cutoff Value	Sensitivity (%)	Specificity (%)
Poor outcome
EMR	0.730 (0.674–0.782)	< 0.001	Ref	≤ 0.05	55.8	89.2
NLR	0.739 (0.683–0.789)	< 0.001	0.790	> 3.41	76.7	66.0
PLR	0.595 (0.535–0.653)	0.011	0.001	> 145.79	50.0	66.0
NLR + EMR	0.752 (0.697–0.802)	< 0.001	0.340	> 0.30	69.8	76.3
Dead
EMR	0.877 (0.832–0.913)	< 0.001	Ref	≤ 0.05	88.9	82.2
NLR	0.810 (0.760–0.855)	< 0.001	0.024	> 4.22	74.1	73.9
PLR	0.619 (0.560–0.676)	0.072	< 0.001	> 220.83	33.3	93.3
NLR + EMR	0.882 (0.838–0.917)	< 0.001	0.615	> 0.13	88.9	81.8

Note: *p for comparison of AUC between groups.

Abbreviations: AUC, area under the curve; CI, confidence interval; EMR, eosinophil to monocyte ratio; NLR, neutrophil to lymphocyte ratio; PLR, platelet to lymphocyte ratio.

Figure 3 (A) Receiver operating characteristic curve (ROC) of EMR, NLR, PLR and NLR + EMR on the prognosis of AIS patients between poor outcome and good outcome. (B) Receiver operating characteristic curve (ROC) of EMR, NLR, PLR and NLR + EMR on the prognosis of AIS patients between death and survive.