From April 2016 to September 2019, a total of 1235 AIS patients treated with intravenous thrombolysis were screened for 24 hours in this study (Additional file 1: Figure S1). Ninety-two patients’ neurological deficits could not be evaluated over the following 24 hours after admission. Meanwhile, eighty-three patients were excluded for the following reasons: nineteen patients were excluded for severe inflammatory or infectious diseases, and sixty-four patients were excluded for incomplete data. A total of 1060 subjects were included for the final analysis.
After admission, post-thrombolysis END was observed in 193 patients (18.2%), and ENI was observed in 398 patients (37.5%), respectively. Baseline characteristics of the study participants according to post-thrombolysis early neurological outcomes (END group, without END or ENI group as well as ENI group) are provided in Table 1. Significant differences among the three group are described as follows: age (P = 0.001), previous antiplatelet (P = 0.002), NIHSS (P = 0.001), diastolic blood pressure (P = 0.034), HT (P = 0.001), OTT (P = 0.002), PAO (P = 0.002), stroke subtype (P = 0.001), FBG (P = 0.001), Hs-CRP (P = 0.001), NLR (P = 0.001), PLR (P = 0.001) and LMR (P = 0.014). Figure 1 showed the violin plots of NLR, PLR and LMR among three groups. NLR decreased gradually among END group, without END or ENI group as well as ENI group (6.09 [4.43, 8.02] versus 4.15 [3.14, 5.26] versus 3.17 [2.54, 4.22], P = 0.001, Fig. 1A). PLR also exhibited different among three groups (179.1 [122.1, 251.1] versus 126.7 [98.8, 158.0] versus 133.1 [102.5, 168.2], P = 0.001, Fig. 1B). LMR increased gradually among three groups (3.03 [2.50, 4.13] versus 3.36 [2.48, 4.34] versus 3.63 [2.61, 4.52], P = 0.014, Fig. 1C).
Table 1
Demographics and Clinical Characteristics of the subgroup according to early neurological outcome
Variable | END group (n = 193) | Without END or ENI group (n = 469) | ENI group (n = 398) | P |
Demographic characteristics | | | | |
Age, years | 73.2 ± 11.5 | 69.6 ± 12.0 | 68.1 ± 12.1 | 0.001 |
Male, n (%) | 121 (62.7) | 319 (68.0) | 260 (65.3) | 0.303 |
BMI, kg/m2 | 24.4 ± 3.6 | 24.1 ± 3.5 | 23.9 ± 3.6 | 0.242 |
Vascular risk factors, n (%) | | | | |
Hypertension | 132 (68.4) | 315 (67.2) | 275 (69.1) | 0.816 |
Diabetes mellitus | 51 (26.4) | 116 (24.7) | 77 (19.3) | 0.079 |
Dyslipidemia | 51 (26.4) | 120 (25.6) | 114 (28.6) | 0.592 |
Atrial fibrillation | 49 (25.4) | 96 (20.5) | 75 (18.8) | 0.180 |
Current smoking | 59 (30.6) | 149 (31.8) | 129 (32.4) | 0.903 |
Current drinking | 69 (35.8) | 145 (30.9) | 129 (32.4) | 0.482 |
Previous stroke | 38 (19.7) | 114 (24.3) | 80 (20.1) | 0.238 |
Peripheral artery disease | 11 (5.7) | 30 (6.3) | 30 (7.5) | 0.662 |
Coronary artery disease | 38 (19.7) | 83 (17.7) | 81 (20.4) | 0.603 |
Medication use history, n (%) | | | | |
Previous antiplatelet | 21 (10.9) | 88 (18.8) | 91 (22.9) | 0.002 |
Previous anticoagulation | 15 (7.8) | 49 (10.4) | 42 (10.6) | 0.521 |
Previous statin | 5 (2.6) | 11 (2.3) | 5 (1.3) | 0.391 |
Clinical assessment | | | | |
NIHSS, score | 11 (5, 17) | 5 (3, 12) | 8 (4, 14) | 0.001 |
SBP, mmHg | 146.9 ± 23.6 | 151.8 ± 25.7 | 148.3 ± 22.6 | 0.171 |
DBP, mmHg | 87.8 ± 16.2 | 89.4 ± 14.4 | 86.8 ± 14.6 | 0.034 |
HT, n (%) | 32 (16.6) | 37 (7.9) | 13 (3.3) | 0.001 |
OTT, minute | 165.00 (120.00, 200.00) | 160.00 (115.00, 200.00) | 130.00 (90.00, 180.00) | 0.001 |
PAO, % | 77 (39.9) | 134 (28.6) | 91 (22.9) | 0.001 |
Endovascular treatment, % | 43 (22.2) | 77 (16.4) | 65 (16.3) | 0.148 |
Stroke subtype, n (%) | | | | 0.001 |
LAA | 73 (37.8) | 169 (36.0) | 147 (36.9) | |
CE | 62 (32.1) | 120 (25.6) | 132 (33.2) | |
SAO | 27 (14.0) | 138 (29.4) | 83 (20.9) | |
SOE | 8 (4.1) | 16 (3.4) | 8 (2.0) | |
SUE | 23 (12.0) | 26 (5.6) | 28 (7.0) | |
Lesion location, n (%) | | | | 0.616 |
Anterior circulation | 149 (77.2) | 357 (76.1) | 294 (73.9) | |
Posterior circulation | 44 (22.8) | 112 (23.9) | 104 (20.1) | |
Laboratory data | | | | |
TC, mmol/L | 4.41 ± 1.11 | 4.38 ± 1.11 | 4.32 ± 1.10 | 0.591 |
TG, mmol/L | 1.14 (0.82, 1.68) | 1.19 (0.86, 1.70) | 1.20 (0.85, 1.75) | 0.744 |
HDL, mmol/L | 1.21 ± 0.68 | 1.14 ± 0.36 | 1.13 ± 0.49 | 0.214 |
LDL, mmol/L | 2.53 (1.95, 3.20) | 2.63 (1.98, 3.23) | 2.59 (1.96, 3.27) | 0.733 |
FBG, mmol/L | 7.30 ± 2.95 | 6.28 ± 2.47 | 6.86 ± 3.19 | 0.001 |
Hs-CRP, mg/L | 7.25 (2.66, 14.55) | 4.28 (2.11, 7.55) | 4.85 (2.16, 8.61) | 0.001 |
NLR | 6.09 (4.43, 8.02) | 4.15 (3.14, 5.26) | 3.17 (2.54, 4.22) | 0.001 |
PLR | 179.1 (122.1, 251.1) | 126.7 (98.8, 158.0) | 133.1 (102.5, 168.2) | 0.001 |
LMR | 3.03 (2.50, 4.13) | 3.36 (2.48, 4.34) | 3.63 (2.61, 4.52) | 0.014 |
Abbreviation: END, early neurological deterioration; ENI, Early neurological improvement; BMI, body mass index; NIHSS, national institute of health stroke scale; SBP, systolic blood pressure; DBP, diastolic blood pressure; HT, hemorrhagic transformation; OTT, onset to treatment time; PAO, proximal arterial occlusion; 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; LDL, low-density lipoprotein; HDL, high density lipoprotein; FBG, fasting blood glucose; Hs-CRP, hyper-sensitive c-reactive protein; NLR, neutrophil-lymphocyte ratio; PLR. platelet-lymphocyte ratio; LMR, lymphocyte-monocyte ratio. |
Table 2 illustrated the results of univariate logistic regression analysis for post-thrombolysis END and post-thrombolysis ENI. Univariate logistic regression analysis for END showed that age, atrial fibrillation, previous antiplatelet, NIHSS, HT, OTT, PAO, endovascular treatment, stroke subtype, FBG, Hs-CRP, NLR, PLR and LMR might be associated with post-thrombolysis END (P < 0.1). Furthermore, Univariate logistic regression analysis also exhibited that age, diabetes mellitus, previous antiplatelet, diastolic blood pressure, HT, OTT, PAO, NLR, PLR and LMR might be related to post-thrombolysis ENI (P < 0.1).
Table 2
Univariate Logistic regression analysis for risk factors with post-thrombolysis END and post-thrombolysis ENI
| Crude model for post-thrombolysis END | Crude model for post-thrombolysis ENI |
Variable | OR (95%CI) | P | OR (95%CI) | P |
Demographic characteristics | | | | |
Age, years | 1.033 (1.018–1.048) | 0.001 | 0.982 (0.972–0.993) | 0.002 |
Male, n (%) | 0.813 (0.587–1.125) | 0.211 | 0.950 (0.729–1.237) | 0.702 |
BMI, kg/m2 | 1.032 (0.987–1.079) | 0.169 | 0.974 (0.940–1.010) | 0.159 |
Vascular risk factors, n (%) | | | | |
Hypertension | 1.033 (0.737–1.447) | 0.851 | 1.070 (0.819–1.399) | 0.629 |
Diabetes mellitus | 1.254 (0.877–1.794) | 0.215 | 0.711 (0.524–0.964) | 0.028 |
Dyslipidemia | 0.972 (0.682–1.383) | 0.873 | 1.153 (0.872–1.523) | 0.317 |
Atrial fibrillation | 1.385 (0.962–1.995) | 0.080 | 0.828 (0.606–1.130) | 0.235 |
Current smoking | 0.933 (0.665–1.308) | 0.687 | 1.047 (0.802–1.366) | 0.737 |
Current drinking | 1.204 (0.868–1.671) | 0.226 | 1.004 (0.770–1.309) | 0.977 |
Previous stroke | 0.847 (0.574–1.249) | 0.402 | 0.848 (0.625–1.150) | 0.288 |
Peripheral artery disease | 0.813 (0.419–1.577) | 0.540 | 1.235 (0.758–2.012) | 0.397 |
Coronary artery disease | 1.049 (0.708–1.555) | 0.810 | 1.140 (0.833–1.561) | 0.412 |
Medication use history, n (%) | | | | |
Previous antiplatelet | 0.469 (0.290–0.760) | 0.002 | 1.504 (1.102–2.053) | 0.010 |
Previous anticoagulation | 1.415 (0.512–3.909) | 0.504 | 0.514 (0.187–1.413) | 0.197 |
Previous statin | 0.848 (0.638–1.127) | 0.256 | 1.050 (0.855–1.289) | 0.642 |
Clinical assessment | | | | |
NIHSS, score | 1.051 (1.030–1.072) | 0.001 | 1.007 (0.990–1.024) | 0.446 |
SBP, mmHg | 0.995 (0.989–1.002) | 0.195 | 0.998 (0.993–1.002) | 0.359 |
DBP, mmHg | 0.998 (0.993–1.009) | 0.737 | 0.990 (0.982–0.999) | 0.023 |
HT, n (%) | 3.248 (2.020–5.221) | 0.001 | 0.290 (0.158–0.532) | 0.001 |
OTT, minute | 1.004 (1.001–1.006) | 0.011 | 0.993 (0.990–0.995) | 0.001 |
PAO, % | 1.894 (1.368–2.623) | 0.001 | 0.634 (0.476–0.843) | 0.002 |
Endovascular treatment, % | 1.464 (0.997–2.148) | 0.052 | 0.882 (0.633–1.228) | 0.456 |
Stroke subtype, n (%) | | | | |
LAA | Reference | | Reference | |
CE | 1.065 (0.731–1.552) | 0.743 | 1.194 (0.881–1.618) | 0.252 |
SAO | 0.529 (0.329–0.849) | 0.008 | 0.828 (0.592–1.157) | 0.268 |
SOE | 1.443 (0.623–3.341) | 0.392 | 0.549 (0.240–1.253) | 0.154 |
SUE | 1.844 (1.063–3.197) | 0.029 | 0.941 (0.566–1.563) | 0.813 |
Lesion location, n (%) | | | | |
Anterior circulation | 1.124 (0.776–1.626) | 0.537 | 0.872 (0.654–1.161) | 0.347 |
Posterior circulation | 0.890 (0.615–1.288) | 0.537 | 1.147 (0.861–1.528) | 0.347 |
Laboratory data | | | | |
TC, mmol/L | 1.003 (0.996–1.010) | 0.447 | 0.999 (0.994–1.003) | 0.591 |
TG, mmol/L | 1.000 (0.998–1.002) | 0.623 | 1.001 (0.996–1.005) | 0.655 |
HDL, mmol/L | 1.255 (0.953–1.654) | 0.106 | 0.889 (0.664–1.190) | 0.428 |
LDL, mmol/L | 0.999 (0.992–1.005) | 0.708 | 1.002 (0.998–1.005) | 0.415 |
FBG, mmol/L | 1.084 (1.032–1.138) | 0.002 | 1.035 (0.991–1.080) | 0.119 |
Hs-CRP, mg/L | 1.033 (1.018–1.048) | 0.001 | 0.997 (0.984–1.010) | 0.630 |
NLR | 1.661 (1.528–1.807) | 0.001 | 0.678 (0.626–0.735) | 0.001 |
PLR | 1.014 (1.011–1.017) | 0.001 | 0.997 (0.995–0.999) | 0.004 |
LMR | 0.869 (0.758–0.996) | 0.043 | 1.152 (1.033–1.284) | 0.011 |
Abbreviation: END, early neurological deterioration; ENI, Early neurological improvement; OR, odds ratio; CI, confidence interval; BMI, body mass index; NIHSS, national institute of health stroke scale; SBP, systolic blood pressure; DBP, diastolic blood pressure; HT, hemorrhagic transformation; OTT, onset to treatment time; PAO, proximal arterial occlusion; 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; LDL, low-density lipoprotein; HDL, high density lipoprotein; FBG, fasting blood glucose; Hs-CRP, hyper-sensitive c-reactive protein; NLR, neutrophil-lymphocyte ratio; PLR. platelet-lymphocyte ratio; LMR, lymphocyte-monocyte ratio. |
Table 3 displayed the results of the multivariate logistic regression model for post-thrombolysis END. In the multivariate logistic regression model including NLR (Model 1), NLR was identified as an independent factor for post-thrombolysis END (odds ratio [OR], 1.652; 95% confidence interval [CI] 1.510–1.807, P = 0.001) after adjustment for all potential confounders. In the multivariate logistic regression model including PLR (Model 2), PLR remained an independent factor for post-thrombolysis END (OR, 1.015; 95% CI 1.012–1.018, P = 0.001). However, in the multivariate logistic regression model including LMR (Model 3), it showed that LMR was not the independent factor for post-thrombolysis END (OR, 0.880; 95% CI 0.760–1.020, P = 0.090).
Table 3
Logistic regression NLR model, PLR model and LMR model of post-thrombolysis END
| Model 1: association of NLR with post-thrombolysis END | Model 2: association of PLR with post-thrombolysis END | Model 3: association of LMR with post-thrombolysis END |
Variable | OR (95%CI) | P | OR (95%CI) | P | OR (95%CI) | P |
Age | 1.018 (1.001–1.035) | 0.038 | 1.028 (1.011–1.045) | 0.001 | 1.023 (1.007–1.039) | 0.004 |
Atrial fibrillation | 1.014 (0.613–1.676) | 0.957 | 1.185 (0.729–1.926) | 0.494 | 1.038 (0.657–1.640) | 0.874 |
Previous antiplatelet | 0.526 (0.302–0.915) | 0.023 | 0.544 (0.320–0.927) | 0.025 | 0.462 (0.278–0.767) | 0.003 |
NIHSS | 1.029 (1.004–1.056) | 0.025 | 1.030 (1.005–1.056) | 0.019 | 1.029 (1.006–1.053) | 0.014 |
HT | 1.973 (1.102–3.534) | 0.022 | 2.892 (1.621–5.161) | 0.001 | 2.581 (1.536–4.337) | 0.001 |
OTT | 1.004 (1.001–1.008) | 0.011 | 1.005 (1.001–1.008) | 0.007 | 1.004 (1.001–1.007) | 0.012 |
PAO | 1.890 (1.107–3.226) | 0.020 | 2.014 (1.195–3.395) | 0.009 | 2.032 (1.263–3.270) | 0.003 |
Endovascular treatment | 0.631 (0.335–1.188) | 0.154 | 0.661 (0.355–1.229) | 0.191 | 0.623 (0.353–1.098) | 0.102 |
Stroke subtype | | | | | | |
LAA | Reference | | Reference | | Reference | |
CE | 0.954 (0.579–1.573) | 0.854 | 0.823 (0.506–1.337) | 0.437 | 0.829 (0.527–1.304) | 0.417 |
SAO | 0.671 (0.388–1.163) | 0.155 | 0.701 (0.408–1.202) | 0.197 | 0.644 (0.389–1.068) | 0.088 |
SOE | 2.576 (0.956–6.944) | 0.061 | 2.074 (0.790–5.444) | 0.139 | 1.686 (0.703–4.040) | 0.242 |
SUE | 1.907 (0.967–3.764) | 0.063 | 1.643 (0.857–3.147) | 0.135 | 1.459 (0.795–2.677) | 0.222 |
FBG | 1.073 (1.009–1.141) | 0.024 | 1.080 (1.018–1.145) | 0.011 | 1.083 (1.026–1.144) | 0.004 |
Hs-CRP | 1.030 (1.012–1.047) | 0.001 | 1.024 (1.008–1.041) | 0.004 | 1.024 (1.009–1.039) | 0.002 |
Composite inflammatory ratio* | 1.652 (1.510–1.807) | 0.001 | 1.015 (1.012–1.018) | 0.001 | 0.880 (0.760–1.020) | 0.090 |
* In the Model 1: ‘composite inflammatory ratio’ means NLR; |
In the Model 2: ‘composite inflammatory ratio’ means PLR; |
In the Model 3: ‘composite inflammatory ratio’ means LMR; |
Abbreviation: NLR, neutrophil-lymphocyte ratio; PLR. platelet-lymphocyte ratio; LMR, lymphocyte-monocyte ratio; END, early neurological deterioration; OR, odds ratio; CI, confidence interval; NIHSS, national institute of health stroke scale; HT, hemorrhagic transformation; OTT, onset to treatment time; PAO, proximal arterial occlusion; LAA, large-artery atherosclerosis; CE, cardioembolism; SAO, small-artery occlusion; SOE: stroke of other determined etiology; SUE: stroke of undetermined etiology; FBG, fasting blood glucose; Hs-CRP, hyper-sensitive c-reactive protein. |
Table 4 manifested the results of the multivariate logistic regression model for post-thrombolysis ENI. In the multivariate logistic regression model including NLR (Model 4), NLR was identified as an independent factor for post-thrombolysis ENI (OR, 0.686; 95% CI 0.631–0.745, P = 0.001) after adjustment for all potential confounders. In the multivariate logistic regression model including PLR (Model 5), PLR remained an independent factor for post-thrombolysis END (OR, 0.997; 95% CI 0.994–0.999, P = 0.006). What is more, in the multivariate logistic regression model including LMR (Model 6), LMR was found to be the independent factor for post-thrombolysis ENI (OR, 1.170; 95% CI 1.043–1.313, P = 0.008).
Table 4
Logistic regression NLR model, PLR model and LMR model of post-thrombolysis ENI
| Model 4: association of NLR with post-thrombolysis ENI | Model 5: association of PLR with post-thrombolysis ENI | Model 6: association of LMR with post-thrombolysis ENI |
Variable | OR (95%CI) | P | OR (95%CI) | P | OR (95%CI) | P |
Age | 0.984 (0.973–0.995) | 0.006 | 0.982 (0.971–0.993) | 0.001 | 0.982 (0.972–0.993) | 0.001 |
Diabetes mellitus | 0.702 (0.503–0.978) | 0.036 | 0.684 (0.497–0.942) | 0.020 | 0.691 (0.502–0.951) | 0.023 |
Previous antiplatelet | 1.426 (1.008–2.015) | 0.045 | 1.522 (1.091–2.122) | 0.013 | 1.565 (1.123–2.181) | 0.008 |
DBP | 0.986 (0.977–0.996) | 0.005 | 0.988 (0.979–0.997) | 0.011 | 0.989 (0.980–0.998) | 0.013 |
HT | 0.417 (0.219–0.795) | 0.008 | 0.332 (0.177–0.620) | 0.001 | 0.326 (0.174–0.609) | 0.001 |
OTT | 0.992 (0.990–0.995) | 0.001 | 0.993 (0.990–0.995) | 0.001 | 0.993 (0.990–0.995) | 0.001 |
PAO | 0.714 (0.521–0.977) | 0.036 | 0.666 (0.492-0.900) | 0.008 | 0.667 (0.493–0.901) | 0.008 |
Composite inflammatory ratio* | 0.686 (0.631–0.745) | 0.001 | 0.997 (0.994–0.999) | 0.006 | 1.170 (1.043–1.313) | 0.008 |
* In the Model 4: ‘composite inflammatory ratio’ means NLR; |
In the Model 5: ‘composite inflammatory ratio’ means PLR; |
In the Model 6: ‘composite inflammatory ratio’ means LMR; |
Abbreviation: NLR, neutrophil-lymphocyte ratio; PLR. platelet-lymphocyte ratio; LMR, lymphocyte-monocyte ratio; ENI, Early neurological improvement; OR, odds ratio; CI, confidence interval; NIHSS, national institute of health stroke scale; DBP, diastolic blood pressure; HT, hemorrhagic transformation; OTT, onset to treatment time; PAO, proximal arterial occlusion. |
ROC curves, which were depicted in Fig. 2, were used to test the overall discriminative ability of these three composite inflammatory ratios for outcomes. We observed that the area under curve (AUC) of NLR, PLR and LMR to discriminate post-thrombolysis END were 0.763 (95% CI, 0.736–0.788), 0.703 (95% CI, 0.675–0.730) and 0.551 (95% CI, 0.521–0.581) (Fig. 2A). To predict post-thrombolysis END, AUC of NLR was superior to PLR (0.763 versus 0.703, P = 0.010) and LMR (0.763 versus 0.551, P = 0.001).Moreover, AUC of PLR was superior to LMR (0.703 versus 0.551, P = 0.001) Meanwhile, the AUC of NLR, PLR and LMR to discriminate post-thrombolysis ENI were 0.695 (95% CI, 0.666–0.722), 0.530 (95% CI, 0.499–0.560) and 0.547 (95% CI, 0.516–0.577) (Fig. 2B). To predict post-thrombolysis ENI, AUC of NLR was superior to PLR (0.695 versus 0.530, P = 0.001) and LMR (0.695 versus 0.547, P = 0.001). However, there was not significant difference between the AUC of PLR and LMR (0.530 versus 0.547, P = 0.461) We also established optimal cutoff values at which the Youden index was highest. The details of optimal cutoff values for NLR, PLR and LMR as predictors of post-thrombolysis END and ENI were described in Additional file 2: Table S1.