Neutrophil to High-Density Lipoprotein Ratio is Associated with Hemorrhagic Transformation in Patients with Acute Ischemic Stroke

Figures & data

Figure 1 Flow chart of the study selection.

Abbreviation: HT, hemorrhagic transformation.

Figure 2 ROC curves of NHR, leukocyte, neutrophil, HDL-C and NIHSS on admission predicting HT. Data were analyzed with SPSS statistics software by Ruirui Zhang.

Abbreviations: NHR, neutrophil to high-density lipoprotein ratio; ROC, Receiver operating characteristic, NIHSS, National Institutes of Health Stroke Scale, HDL-C, high-density lipoprotein cholesterol.

Figure 3 Stratified logistic regression analysis model to explore variables affecting the correlation between NHR and HT. Above model adjusted for age, sex, atrial fibrillation, alcohol consumption, smoking, NIHSS, SBP, LDL-C, glucose, and stroke subtype.

Notes: In each subgroup analysis, the model was not adjusted for stratification variables.

Abbreviations: NHR, neutrophil to high-density lipoprotein ratio; HT, hemorrhagic transformation; OR, odds ratio; NIHSS, National Institutes of Health Stroke Scale; SBP, systolic blood pressure; LDL-C, low-density lipoprotein cholesterol.

Figure 4 Correlation between age and neutrophils and HDL-C in AIS patients (A and B). (A) There was a positive correlation between age and HDL-C: r = 0.107, P = 0.004; (B) There was no correlation between age and neutrophils: r = 0.031, P = 0.407.

Abbreviation: HDL-C, high-density lipoprotein cholesterol.

Table 1 Baseline Characteristics and Clinical Data of Enrolled Patients

Characteristics	HT (n=87)	No-HT (n=638)	P-value
Demographics
Age (years), mean ± SD	70.68±10.21	65.77±11.55	<0.001
Male, n (%)	58.62	62.23	0.557
Hypertension, n (%)	63.22	67.40	0.467
Diabetes, n (%)	25.29	28.21	0.612
Atrial fibrillation, n (%)	37.93	12.23	<0.001
Prior stroke, n (%)	18.40	20.85	0.673
Dyslipidemia, n (%)	24.29	22.99	0.894
Smoking, n (%)	24.14	28.68	0.446
Alcohol consumption, n (%)	17.24	22.41	0.333
NIHSS, median (IQR)	11 (5–17)	4 (3–7)	<0.001
Leukocyte (×109/L), median (IQR)	7.90 (6.10–9.60)	6.70 (5.50–8.13)	<0.001
Neutrophil (×109/L), median (IQR)	6.20 (4.10–7.60)	4.40 (3.50–5.90)	<0.001
Platelet (×109/L), median (IQR)	156 (126–204)	176.50 (139.75–217.00)	0.015
Hemoglobin (g/L), median (IQR)	127 (118–140)	133.01 (123.00–146.25)	0.004
HDL-C (mmol/L), mean ± SD	1.37±0.32	1.31±0.28	0.054
NHR, median (IQR)	4.31 (3.54–6.24)	3.63 (2.68–4.64)	<0.001
LDL-C (mmol/L), mean ± SD	2.32±0.87	2.55±0.85	0.017
TC (mmol/L), mean ± SD	4.22±1.08	4.34±0.99	0.302
TG (mmol/L), median (IQR)	1.06 (0.77–1.44)	1.25 (0.89–1.74)	<0.001
Urea (mmol/L), median (IQR)	6.02 (4.94–7.46)	5.70 (4.60–6.79)	0.06
Creatinine (umol/L), median (IQR)	70.20 (53.20–81.90)	67.30 (56.13–79.83)	0.415
Uric acid (umol/L), mean ± SD	318.95±107.45	348.08±100.86	0.012
Glucose (mmol/L), median (IQR)	6.32 (4.99–7.63)	5.49 (4.68–7.37)	0.044
D-dimer (ug/L), median (IQR)	1.10 (0.47–2.52)	0.39 (0.24–0.89)	<0.001
SBP, mmHg (mean ± SD)	155.64±26.34	154.09±23.81	0.576
DBP, mmHg, median (IQR)	84 (77–92)	85 (77–94)	0.90
Treatments during hospital
Antiplatelets, n (%)	83.91	96.55	0.001
Anticoagulants, n (%)	21.84	8.62	<0.001
Thrombolysis, n (%)	13.80	5.33	0.005
Thrombectomy, n (%)	3.45	1.72	0.23
TOAST classification, n (%)			<0.001
Large-artery atherosclerosis	52.87	69.12
Cardioembolic	42.53	12.85
Small-artery occlusion	2.30	15.05
Other etiology	1.15	2.51
Undetermined etiology	1.15	0.47

Abbreviations: HT, hemorrhagic transformation; NIHSS, National Institutes of Health Stroke Scale; HDL-C, high-density lipoprotein cholesterol; NHR, neutrophil to high-density lipoprotein ratio; LDL-C, low-density lipoprotein cholesterol; TC, total cholesterol; TG, triglyceride; SBP, systolic blood pressure; DBP, diastolic blood pressure; TOAST, the Trial of ORG 10,172 in Acute Stroke Treatment.

Table 2 The Predictive Value of NHR for HT in AIS Patients

Variables	Best Predicted value	Sensitivity (%)	Specificity (%)	AUC (95% CI)	P-value
NHR	3.52	77.0	52.8	0.633 (0.567–0.699)	<0.001
Leukocyte	7.15	64.4	58.5	0.630 (0.567–0.693)	<0.001
Neutrophil	5.65	62.1	72.6	0.681 (0.618–0.744)	<0.001
HDL-C	1.39	44.8	68.0	0.554 (0.488–0.621)	0.099
NIHSS	10.5	50.6	87.9	0.724 (0.660–0.789)	<0.001

Abbreviations: AUC, area under the curve; CI, confidence interval; NHR, neutrophil to high-density lipoprotein ratio; HDL-C, high-density lipoprotein cholesterol; NIHSS, National Institutes of Health Stroke Scale.

Table 3 Multivariate Logistic Analysis to Determine Associations Between NHR Subgroup Levels and HT

NHR	Unadjusted OR (95% CI)	P-value	Adjusted OR (95% CI)*	P-value
NHR quartile group
Q1 (NHR ≤ 2.72)	Ref.	Ref.	Ref.	Ref.
Q2 (NHR 2.72–3.74)	0.741 (0.340–1.614)	0.451	0.831 (0.340–2.032)	0.685
Q3 (NHR 3.74–4.85)	1.281 (0.641–2.559)	0.483	1.501 (0.652–3.458)	0.340
Q4 (NHR > 4.85)	2.849 (1.527–5.316)	0.001	3.157 (1.312–7.596)	0.01
By optimal cut-off derived from the ROC curve
NHR < 3.14	Ref.	Ref.	Ref.	Ref.
NHR ≥ 3.14	2.973 (1.762–5.017)	<0.001	3.434 (1.775–6.644)	<0.001

Notes: *Adjusted for gender, age, NIHSS on admission, prior stroke, atrial fibrillation, D-dimer, hemoglobin, platelet counts, urea, creatinine, uric acid, total cholesterol, triglycerides, high-density lipoprotein, and low-density lipoprotein.

Abbreviations: NHR, neutrophil to high-density lipoprotein ratio; CI, confidence interval; ROC, receiver operating characteristic.

Table 4 Univariate and Multivariate Logistic Regression Analysis for the Risk Factors of HT

Variables	Univariate		Multivariate
	OR (95% CI)	P-value	OR (95% CI)	P-value
Age	1.040 (1.019–1.063)	<0.001	-	0.568
Atrial fibrillation	0.228 (0.139–0.373)	<0.001	2.429 (1.357–4.346)	0.003
NIHSS	1.155 (1.114–1.198)	<0.001	1.097 (1.052–1.145)	<0.001
Leukocyte	1.189 (1.094–1.292)	<0.001	-	0.482
Platelet	0.995 (0.991–0.999)	0.016	0.996 (0.992–1.000)	0.082
Hemoglobin	0.986 (0.976–0.996)	0.008	-	0.347
NHR	1.264 (1.141–1.399)	<0.001	1.180 (1.036–1.344)	0.013
LDL-C	0.712 (0.539–0.941)	0.017	-	0.836
TG	0.478 (0.313–0.730)	0.001	0.684 (0.445–1.052)	0.084
Uric acid	0.997 (0.995–0.999)	0.013	0.997 (0.995–1.000)	0.027
D-dimer	1.207 (1.093–1.333)	<0.001	1.080 (0.995–1.172)	0.065
Antiplatelets	5.370 (2.633–10.951)	<0.001	0.302 (0.130–0.703)	0.006
Anticoagulants	0.338 (0.189–0.602)	<0.001	-	0.553
Thrombolysis	0.352 (0.175–0.709)	0.003	2.250 (0.983–5.155)	0.055

Abbreviations: OR, odds ratio; CI, confidence interval; NIHSS, National Institutes of Health Stroke Scale; NHR, neutrophil to high-density lipoprotein ratio; LDL-C, low-density lipoprotein cholesterol; TG, triglyceride.

Table 5 Correlation Between Neutrophil or HDL-C and Risk Factors of AIS

Variables	Neutrophil		HDL-C
	r/F-value	P-value	r/F-value	P-value
Age	−0.031	0.407	0.107	0.004
Gender	1.015	0.445	1.017	0.438
Hypertension	1.103	0.242	1.258	0.038
Diabetes	0.914	0.713	0.908	0.753
Atrial fibrillation	1.226	0.076	1.368	0.007
Prior stroke	0.914	0.713	0.994	0.508
Dyslipidemia	0.844	0.858	1.047	0.355
Smoking	0.880	0.791	1.102	0.225
Alcohol consumption	1.004	0.476	1.002	0.482

Abbreviation: HDL-C, high-density lipoprotein cholesterol.