Association Between Neutrophil-to-Lymphocyte Ratio/Lymphocyte-to-Monocyte Ratio and In-Hospital Clinical Outcomes in Ischemic Stroke Treated with Intravenous Thrombolysis

Figures & data

Figure 1 Boxplots to show dynamic change trends of NLR (A) and LMR (B).

Table 1 Baseline Characteristics Between No-ENI and ENI Group in Patients Treated with IV tPA

	Overall (n=102)	No-ENI (n=64)	ENI (n=38)	P-value
Age, years (mean (SD))	64.01 (13.02)	64.31 (13.30)	63.50 (12.69)	0.76
Male, n (%)	67 (65.69)	46 (71.88)	21 (55.26)	0.09
DNT time, minutes (median [IQR])	47.50 [35.00–64.00]	47.50 [34.00–64.75]	47.50 [37.25–64.00]	0.80
Time from symptom onset to IV-tPA, minutes (median [IQR])	174.50 [136.50–228.25]	181.50 [150.00–231.25]	156.00 [128.75–208.00]	0.09
Bridging mechanical thrombectomy, n (%)	34 (33.33)	19 (29.69)	15 (39.47)	0.31
Pre-mRS score (%)				0.30
0	81 (79.41)	48 (75.00)	33 (86.84)
1	8 (7.84)	5 (7.81)	3 (7.89)
2	6 (5.88)	6 (9.38)	0 (0.00)
3	4 (3.92)	2 (3.12)	2 (5.26)
4	2 (1.96)	2 (3.12)	0 (0.00)
5	1 (0.98)	1 (1.56)	0 (0.00)
Admission NIHSS score (median [IQR])	9.00 [4.00–12.75]	6.50 [3.00–11.25]	11.50 [8.25–14.00]	0.01
Admission NIHSS score ≤5 (%)	33 (32.35)	29 (45.31)	4 (10.53)	<0.001
Hypertension, n (%)	67 (65.69)	45 (70.31)	22 (57.89)	0.20
Atrial fibrillation, n (%)	19 (18.63)	13 (20.31)	6 (15.79)	0.57
Diabetes mellitus, n (%)	30 (29.41)	23 (35.94)	7 (18.42)	0.06
Hyperlipidemia, n (%)	14 (13.73)	7 (10.94)	7 (18.42)	0.29
Prior stroke, n (%)	27 (26.47)	18 (28.12)	9 (23.68)	0.62
Coronary artery disease, n (%)	18 (17.65)	13 (20.31)	5 (13.16)	0.36
Prior antiplatelet therapy, n (%)	20 (19.61)	12 (18.75)	8 (21.05)	0.78
Prior statin therapy, n (%)	15 (14.71)	10 (15.62)	5 (13.16)	0.73
Smoking, n (%)	59 (57.84)	40 (62.50)	19 (50.00)	0.22
Drinking, n (%)	44 (43.14)	30 (46.88)	14 (36.84)	0.32
TOAST, n (%)				0.78
LAA	67 (65.69)	44 (68.75)	23 (60.53)
CE	26 (25.49)	16 (25.00)	10 (26.32)
SAA	2 (1.96)	1 (1.56)	1 (2.63)
Other	4 (3.92)	2 (3.12)	2 (5.26)
Unknown	3 (2.94)	1 (1.56)	2 (5.26)
Admission SBP level, mmHg (median [IQR])	144.00 [130.00–162.00]	145.50 [130.25–162.00]	140.00 [129.50–153.00]	0.25
Admission DBP level, mmHg (median [IQR])	82.50 [75.00–93.00]	81.00 [75.00–95.00]	83.00 [74.50–90.00]	0.34
Admission serum glucose level, mmol/L (median [IQR])	6.80 [5.55–8.50]	7.40 [5.70–9.40]	6.50 [5.43–7.33]	0.11
HbA1c level, % (median [IQR])	6.10 [5.80–6.60]	6.10 [5.90–6.70]	6.20 [5.70–6.50]	0.61
LDL level, mmol/L (mean (SD))	2.50 (0.86)	2.57 (0.89)	2.38 (0.80)	0.34
Cholesterol level, mmol/L (mean (SD))	4.11 (0.94)	4.18 (0.95)	4.00 (0.93)	0.39
CT hypointensity sign, n (%)	22 (21.57)	13 (20.31)	9 (23.68)	0.69
MCA hyperintensity sign, n (%)	9 (8.82)	5 (7.81)	4 (10.53)	0.92
Fazekas scale (median [IQR])	1.00 [1.00–2.00]	1.00 [1.00–2.00]	1.00 [1.00–1.00]	0.74
Large vessel occlusion, n (%)	32 (31.37)	19 (29.69)	13 (34.21)	0.63
sICH-NINDS, n (%)	9 (8.82)	8 (12.50)	1 (2.63)	0.18
sICH-SITS, n (%)	4 (3.92)	4 (6.25)	0 (0.00)	0.30
NLR at 0 h, 10^9/L (median [IQR])	4.15 [3.08–6.49]	4.27 [3.08–8.79]	3.96 [3.09–5.27]	0.33
NLR at 24 h, 10^9/L (median [IQR])	4.77 [3.27–9.32]	5.62 [3.36–11.64]	4.18 [2.96–6.45]	0.04
LMR at 0 h, 10^9/L (median [IQR])	4.15 [3.02–5.82]	4.00 [2.95–5.83]	4.62 [3.25–5.70]	0.74
LMR at 24 h, 10^9/L (median [IQR])	2.74 [1.98–3.84]	2.45 [1.60–3.54]	3.28 [2.56–4.06]	0.01
NLR change between 0 hrs and 24 h, 10^9/L (median [IQR])	0.68 [−0.45–2.53]	1.13 [−0.22–3.20]	−0.08 [−0.54–1.39]	0.02
LMR change between 0 hrs and 24 h, 10^9/L (median [IQR])	−1.25 [−3.11–−0.01]	−1.26 [−3.31–−0.56]	−0.81 [−1.74–0.28]	0.08

Abbreviations: ENI, early neurological improvement; DNT, door-to-needle; IV, intravenous thrombolysis; tPA, tissue plasminogen activator; mRS, modified Rankin Scale; NIHSS, National Institutes of Health Stroke Scale; TOAST, Trial of Org 10172 in Acute Stroke Treatment; LAA, large atherosclerosis artery; CE, cardiac embolism; SAA, small artery occlusion; SBP, systolic blood pressure; DBP, diastolic blood pressure; LDL, low density lipoprotein; MCA, middle cerebral artery; sICH, symptomatic intracerebral hemorrhage; NINDS, National Institute of Neurological Disorders and Stroke trial; SITS, Safe Implementation of Thrombolysis in Stroke; NLR, neutrophil-to-lymphocyte ratio; LMR, lymphocyte-to-monocyte ratio.

Figure 2 Multivariable logistics regression analyses: (A) adjusted for admission NIHSS score; (B) adjusted for bridging MT, admission NIHSS score and large vessel occlusion.

Table 2 Baseline Characteristics Between mRS 2–6 and mRS 0–1 at Discharge Group in Patients Treated with IV tPA

	Overall (n=102)	mRS 2–6 (n=75)	mRS 0–1 (n=27)	P-value
Age (mean (SD))	64.01 (13.02)	63.31 (12.94)	65.96 (13.29)	0.37
Male, n (%)	67 (65.69)	50 (66.67)	17 (62.96)	0.73
DNT time (median [IQR])	47.50 [35.00–64.00]	48.00 [35.00–64.00]	44.00 [35.50–68.50]	0.99
Time from symptom onset to IV-tPA, min (median [IQR])	174.50 [136.50–228.25]	186.00 [149.00–229.50]	160.00 [115.50–217.50]	0.11
Bridging mechanical thrombectomy, n (%)	34 (33.33)	31 (41.33)	3 (11.11)	0.01
Pre-mRS score (%)				0.91
0	81 (79.41)	58 (77.33)	23 (85.19)
1	8 (7.84)	6 (8.00)	2 (7.41)
2	6 (5.88)	5 (6.67)	1 (3.70)
3	4 (3.92)	3 (4.00)	1 (3.70)
4	2 (1.96)	2 (2.67)	0 (0.00)
5	1 (0.98)	1 (1.33)	0 (0.00)
Admission NIHSS score (median [IQR])	9.00 [4.00–12.75]	9.00 [5.00–14.00]	6.00 [3.00–10.50]	0.04
Admission NIHSS score ≤5 (%)	33 (32.35)	22 (29.33)	11 (40.74)	0.28
Hypertension, n (%)	67 (65.69)	48 (64.00)	19 (70.37)	0.55
Atrial fibrillation, n (%)	19 (18.63)	13 (17.33)	6 (22.22)	0.58
Diabetes mellitus, n (%)	30 (29.41)	23 (30.67)	7 (25.93)	0.64
Hyperlipidemia, n (%)	14 (13.73)	10 (13.33)	4 (14.81)	1
Prior stroke, n (%)	27 (26.47)	21 (28.00)	6 (22.22)	0.56
Coronary artery disease, n (%)	18 (17.65)	12 (16.00)	6 (22.22)	0.67
Prior antiplatelet therapy, n (%)	20 (19.61)	15 (20.00)	5 (18.52)	0.87
Prior statin therapy, n (%)	15 (14.71)	12 (16.00)	3 (11.11)	0.77
Smoking, n (%)	59 (57.84)	41 (54.67)	18 (66.67)	0.28
Drinking, n (%)	44 (43.14)	31 (41.33)	13 (48.15)	0.54
TOAST, n (%)				0.29
LAA	67 (65.69)	50 (66.67)	17 (62.96)
CE	26 (25.49)	18 (24.00)	8 (29.63)
SAA	2 (1.96)	2 (2.67)	0 (0.00)
Other	4 (3.92)	4 (5.33)	0 (0.00)
Unknown	3 (2.94)	1 (1.33)	2 (7.41)
Admission SBP level, mmHg (median [IQR])	144.00 [130.00–162.00]	141.50 [129.25–161.00]	145.00 [139.50–158.50]	0.44
Admission DBP level, mmHg (median [IQR])	82.50 [75.00–93.00]	81.00 [75.00–93.00]	86.00 [76.00–91.50]	0.96
Admission serum glucose level, mmol/L (median [IQR])	6.80 [5.55–8.50]	6.95 [5.88–8.80]	5.70 [5.05–7.35]	0.07
HbA1c level, % (median [IQR])	6.10 [5.80–6.60]	6.20 [5.85–6.85]	6.00 [5.75–6.30]	0.24
LDL level, mmol/L (mean (SD))	2.50 (0.86)	2.42 (0.80)	2.71 (0.97)	0.16
Cholesterol level, mmol/L (mean (SD))	4.11 (0.94)	4.03 (0.93)	4.33 (0.96)	0.20
CT hypointensity sign, n (%)	22 (21.57)	18 (24.00)	4 (14.81)	0.32
MCA hyperintensity sign, n (%)	9 (8.82)	7 (9.33)	2 (7.41)	1
Fazekas scale (median [IQR])	1.00 [1.00–2.00]	1.00 [1.00–2.00]	1.00 [1.00–1.00]	0.94
Large vessel occlusion, n (%)	32 (31.37)	28 (37.33)	4 (14.81)	0.03
sICH-NINDS, n (%)	9 (8.82)	9 (12.00)	0 (0.00)	0.14
sICH-SITS, n (%)	4 (3.92)	4 (5.33)	0 (0.00)	0.52
NLR at 0 h, 10^9/L (median [IQR])	4.15 [3.08–6.49]	4.35 [3.42–7.02]	3.41 [2.60–5.03]	0.03
NLR at 24 h, 10^9/L (median [IQR])	4.77 [3.27–9.32]	5.87 [3.84–10.65]	3.11 [2.52–4.52]	0.01
NLR at 48 h, 10^9/L (median [IQR])	4.92 [2.76– 7.19]	5.72 [3.59–8.14]	2.62 [2.20–4.48]	<0.001
NLR at discharge, 10^9/L (median [IQR])	3.92 [2.68–5.40]	4.43 [3.08–5.89]	2.57 [2.13–3.92]	<0.001
LMR at 0 h, 10^9/L (median [IQR])	4.15 [3.02–5.82]	4.57 [3.13–5.89]	3.81 [2.89–5.28]	0.38
LMR at 24 h, 10^9/L (median [IQR])	2.74 [1.98–3.84]	2.52 [1.80–3.54]	3.45 [2.69–4.92]	0.01
LMR at 48 h, 10^9/L (median [IQR])	2.60 [1.91–3.82]	2.18 [1.75–3.23]	3.70 [2.66–4.31]	<0.001
LMR at discharge, 10^9/L (median [IQR])	2.88 [2.32–3.66]	2.88 [2.28–3.51]	2.96 [2.75–4.91]	0.10
NLR change between 0 h and 24 h, 10^9/L (median [IQR])	0.68 [−0.45–2.53]	1.22 [−0.27–3.27]	−0.10 [−0.83–0.82]	0.01
NLR change between 24 h and 48 h, 10^9/L (median [IQR])	−0.35 [−2.47–0.36]	−0.40 [−2.71–0.55]	−0.34 [−1.41–0.05]	0.99
NLR change between 0 h and discharge, 10^9/L (median [IQR])	−0.61 [−2.09–0.91]	−0.54 [−2.09–1.45]	−0.85 [−2.23–0.48]	0.60
NLR change between 48 h and discharge, 10^9/L (median [IQR])	−0.75 [−2.46–0.91]	−0.83 [−2.94–0.99]	−0.15 [−0.90–0.56]	0.13
LMR change between 0 h and 24 h (median [IQR])	−1.25 [−3.11–−0.01]	−1.33 [−3.40–−0.65]	−0.27 [−1.22–0.27]	0.01
LMR change between 24 h and 48 h, 10^9/L (median [IQR])	−0.08 [−0.74–0.35]	−0.02 [−0.66–0.35]	−0.19 [−0.82–0.23]	0.58
LMR change between 0 h and discharge, 10^9/L (median [IQR])	−1.29 [−2.75–0.02]	−1.45 [−3.00–−0.35]	−0.35 [−1.88–0.33]	0.03
LMR change between 48 h and discharge, 10^9/L (median [IQR])	0.16 [−0.56–1.07]	0.47 [−0.36–1.37]	−0.20 [−1.03–0.48]	0.01

Abbreviations: DNT, door-to-needle; IV, intravenous thrombolysis; tPA, tissue plasminogen activator; mRS, modified Rankin Scale; NIHSS, National Institutes of Health Stroke Scale; TOAST, Trial of Org 10172 in Acute Stroke Treatment; LAA, large atherosclerosis artery; CE, cardiac embolism; SAA, small artery occlusion; SBP, systolic blood pressure; DBP, diastolic blood pressure; LDL, low density lipoprotein; MCA, middle cerebral artery; sICH, symptomatic intracerebral hemorrhage; NINDS, National Institute of Neurological Disorders and Stroke trial; SITS, Safe Implementation of Thrombolysis in Stroke; NLR, neutrophil-to-lymphocyte ratio; LMR, lymphocyte-to-monocyte ratio.

Figure 3 Receiver operating characteristic curves. (A) ROC curve for LMR at 24 hours to predict ENI; (B) ROC curve for NLR at 48 hours to predict favorable functional outcome at discharge; (C) ROC curve for LMR at 48 hours to predict favorable functional outcome at discharge.

Abbreviations: ROC, Receiver operating characteristic curves; LMR, lymphocyte-to-monocyte ratio; ENI, early neurological improvement; NLR, neutrophil-to-lymphocyte ratio.

Figure 4 Distribution of mRS score at discharge between different level of NLR/LMR at 48 hours. Scores range from 0–6, with 0 indicating no symptoms, 1 no clinically significant disability, 2 slight disability (patients are able to look after their own affairs without assistance but are unable to carry out all previous activities), 3 moderate disability (patients require some help but are able to walk unassisted), 4 moderately severe disability (patients are unable to attend to bodily needs without assistance and are unable to walk unassisted), 5 severe disability (patients require constant nursing care and attention), and 6 death. (A) For NLR at 48 hours, high level of NLR at 48 hours represented poor functional outcome at discharge, common OR was 0.09 and 95% CI was 1.54–3.18 (P<0.001). (B) For LMR at 48 hours, high level of LMR at 48 hours represented favorable functional outcome at discharge, common OR was 7.87 and 95% CI was 1.27−2.85 (P<0.001).