Evaluation of plasma levels of neopterin and soluble CD40 ligand in patients with acute ischemic stroke in upper Egypt: can they surrogate the severity and functional outcome?

Figures & data

Table 1 Basic characteristics of the study patients with acute ischemic stroke

Parameters	Patients (n=100)	Controls (n=25)
Age/years (mean ± SD)	60.6±9.7	58.5±5.7
Sex (male/female) (%)	44/56 (44%/56%)	12/13 (48%/52%)
Duration of stroke (hours)	18.9±10.7
mRS (90 days later) (mean ± SD, median)	3.7±1.5, 4
SSS (mean ± SD, median)	25.3±14.8, 20
Number of deaths	24 (24%)
Vascular risk factors (No [%])
Hypertension	64 (64%)
SBP (mm Hg)	144.8±17
DBP (mm Hg)	84.8±7.6
Dyslipidemia	60 (60%)
Diabetes mellitus	36 (36%)
Smoking	40 (40%)
Ischemic heart disease	12 (12%)
Non-valvular atrial fibrillation	84 (84%)
Stroke etiology (No [%])
Small vessel occlusion	60 (60%)
Cardio-embolism	40 (40%)
Abnormal carotid duplex (No [%])	68 (68%)
Abnormal vertebrobasilar duplex (No [%])	24 (24%)
Laboratory investigations	Mean ± SD
TC (mmol/L)	214.9±49.9	199±48.4
LDL-C (mmol/L)	141.8±58.5	112±28.2
HDL-C (mmol/L)	48.6±10.5	44±8.8
TG (mmol/L)	132.5±50.9	115±60.3
RBG (mg/dL)	144.3±69.3	111.7±14.2
ESR (minutes)	54.3±21.8	70.0±11.9

Abbreviations: ESR, erythrocyte sedimentation rate; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; mRS, modified Rankin Scale; RBG, random blood glucose; SSS, Scandinavian stroke scale; TC, total cholesterol; TG, triglycerides.

Table 2 The mean levels of inflammatory markers in all patients with ischemic stroke compared to controls

Parameters	Patients (n=100)	Controls (n=25)	P-value*
	Mean ± SD
CRP (mg/dL)	4.8±1.6	2.7±1.7	0.001
Neopterin (nmol/L)	16.04±3.8	1.3±0.2	0.001
sCD40 ligand (ng/mL)	8.2±1.9	0.8±0.6	0.001

Note:

* Student’s t-test was used to compare the mean difference between groups. Abbreviations: CRP, C-reactive protein; sCD40, soluble CD40.

Figure 1 Mean serum levels of (A) neopterin and (B) sCD40 ligand in acute ischemic stroke patients with favorable and unfavorable outcomes 90 days later. Error bars indicate 95% CI values.

Abbreviation: sCD40, soluble CD40.

Table 3 Distribution of serum neopterin and sCD40 ligand levels in stroke patients with favorable and unfavorable outcomes (90 days later)

Parameters	mRS (90 days later) (n=100)		P-valuea
	Favorable (n=4)	Unfavorable (n=96)
Neopterin (mean ± SD)	16±3.6	16.1±3.8	0.7
sCD40 ligand (mean ± SD)	8±0.6	8.2±2.1	0.3

Note:

a Student’s t-test was used to compare the mean difference between groups.

Abbreviations: mRS, modified Rankin Scale; sCD40, soluble CD40.

Figure 2 Mean serum levels of (A) neopterin and (B) sCD40 ligand in survivors and those who died with acute ischemic stroke. Error bars indicate 95% CI values. Abbreviation: sCD40, soluble CD40.

Table 4 Distribution of serum neopterin and sCD40 Ligand levels according to survival status

Parameters	Survivors (n=76)	Deaths (n=24)	P-valuea
	(Mean ± SD)
Serum neopterin (nmol/L)	16±3.8	18±5.2	0.001
Serum sCD40 ligand (ng/mL)	8±1.35	10±2.28	0.001

Note:

a P-value is significant if<0.05.

Abbreviation: sCD40, soluble CD40.

Figure 3 The ROC curve showed the optimal cutoff value of serum (A) neopterin levels, (B) sCD40 ligand levels, and (C) CRP levels as an indicator for prediction of poor functional outcome and mortality.

Abbreviations: CRP, C-reactive protein; ROC, receiver operating characteristic; sCD40, soluble CD40.

Table 5 Prediction of functional outcome and mortality in AIS patients

Parameter	Neopterin	sCD40 ligand	CRP
AUC	75.4%	83.3%	85.1%
95% CI	0.65–0.85	0.70–0.96	0.76–0.94
Cutoff	>16.5 nmol/L	>8.5 ng/mL	>2.5 mg/dL
P-value	0.001	0.001	0.001
Sensitivity	100%	100%	100%
Specificity	94.7%	94.7%	63.2%

Abbreviations: AIS, acute ischemic stroke; AUC, area under the curve; CRP C-reactive protein; sCD40, soluble CD40.

Figure 4 Correlation between mean serum levels of (A) neopterin and (B) sCD40 ligand with functional outcome assessed by modified Rankin Scale (mRS), and (C) correlation between mean serum levels of neopterin and sCD40 ligand. Abbreviation: sCD40, soluble CD40.

Table 6 Correlation of the serum levels of neopterin, sCD40 ligand, and CRP with the stroke severity and the functional outcome in patients with ischemic stroke

Parameters	mRS		Neopterin		sCD40 ligand		CRP
	ra	P-value	r	P-value	r	P-value	r	P-value
SSS			−0.126	0.211	−0.285	0.004	−0.252	0.012
Neoptrin	0.278	0.005			0.425	0.001	0.330	0.001
sCD40 ligand	0.490	0.001	0.425	0.001			0.171	0.001
CRP	0.402	0.001	0.330	0.001	0.171	0.001

Note:

a r=correlation coefficient.

Abbreviations: CRP, C-reactive protein; mRS, modified Rankin Scale; sCD40, soluble CD40; SSS, Scandinavian Stroke Scale.

Table 7 Correlation of the serum levels of neopterin and sCD40 ligand with the risk factors of stroke in patients with ischemic stroke

Risk factors	Neopterin		sCD40 ligand
	R	P-value	r	P-value
Hypertension	0.006	0.49	0.117	0.001
Diabetes mellitus	0.046	0.033	0.1	0.001
Dyslipidemia	0.003	0.574	0.185	0.001
Smoking	0.010	0.322	0.046	0.032
Ischemic heart disease	0.026	0.112	6.734	0.798
Atrial fibrillation	0.032	0.075	1.323	0.91
Abnormal carotid duplex	0.071	0.007	0.089	0.003
Abnormal vertebrobasilar duplex	0.093	0.049	0.025	0.798

Notes: R=correlation coefficient. Bold values indicate statistical significance.

Abbreviation: sCD40, soluble CD40.

Table 8 Multivariate logistic regression analysis for determining the role of neopterin, sCD40 ligand, and CRP in predicting mortality in our patients with acute ischemic stroke

Variables	AOR	95% CI	P-value
Age/years	1.13	0.99–1.28	0.068
Sex (female)	1.80	0.62–6.35	0.531
Neopterin	1.53	0.98–2.39	0.062
sCD40L	2.65	1.03–6.81	0.043
CRP	2.51	1.15–5.51	0.022

Notes: The model included age and sex as a priori factors in addition to the significant factors in the univariate analysis. Bold values indicate statistical significance.

Abbreviations: AOR, adjusted odds ratio; CRP, C-reactive protein; sCD40L, soluble CD40 ligand.