In our study, we tried to study EFT, NLR, and VWF in acute ischemic stroke, and our hypothesis in this is that EFT, NLR, and VWF can be considered strong predictors of stroke occurrence, stroke severity, and stroke prognosis.
In our study, the majority of acute ischemic stroke patients (61.7%) had moderate to severe stroke (NIHSS ≥ 5) on admission. The NIHSS ≥ 5 in those who had moderate to severe acute ischemic stroke was significantly more prevalent among patients with diabetes (DM) (p value 0.001), hypercholesterolemia, (p value 0.008), and NLR ≥ 2 (p value 0.001), and that came in agreement with Esref and colleagues [10].
Akil and colleagues reported for the first time the association between ischemic stroke and EFT [4]. EFT plays important role in atherosclerosis and stroke by increasing inflammatory mediators and other thrombo embolic risk factors [5].
EFT (p value, 0.001) was higher in the patients group than the control one and that came in the agreement of Ibrahim and colleagues [11]. However, on binary logistic regression analysis for relevant risk factors after adjustment of BMI, hypercholesterolemia, carotid artery stenosis, NLR, and VWF:Ag level, EFT was not a significant risk factor in acute ischemic stroke patients compared to NLR and VWF:Ag level that were highly significant risk factors for ischemic stroke and that came in agreement with Wang and colleagues [12]. Also, there was no statistical significance between stroke severity and EFT and that came in agreement with Esref and colleagues [10].
On MRS done 3 months from acute ischemic stroke onset, there was no statistical significance between post ischemic stroke disability and initial EFT, but that did not come in agreement with Ibrahim and colleagues [11]. The difference in results can be explained by fewer number of patients group in this study and difference in clinical presentations of acute ischemic strokes between the two studies.
EFT ≥ 5 was significantly more prevalent among those with hypertension (p value 0.019), hypercholesterolemia (p value 0.001), BMI, (p value 0.001), and combined risk factors > 2 (p value 0.029) and that came in the agreement of Ibrahim and colleagues and Sengul and colleagues [11, 13]. However, Hikmet and colleagues [14] found that the association of EFT and metabolic syndrome constituents was stronger for body mass index than lipid parameters. EFT had no significant relationship in those with atrial fibrillation but that did not come in agreement with Jin-Hyung and colleagues [15] and Chu and colleagues [16]. This can be explained by fewer number of ischemic stroke patients with atrial fibrillation in this study. EFT had no significant relationship in those with diabetes mellitus. However, Hikmet and colleagues [14] showed that echocardiographic EFT was significantly associated with all indices of insulin resistance and glucose intolerance. Also, EFT had no significant relationship in those with carotid artery stenosis, but that did not come in agreement with Sengul and colleagues’ [13] explanation is that fewer number of patients with carotid artery stenosis in this study.
NLR ≥ 2 was significantly more prevalent among patients with DM (p value 0.001) and hypercholesterolemia (p value 0.01), while NLR ≥ 2 was not significant in relation to smoking, hypertension, BMI, carotid artery stenosis, blood group, hyperuricemia, and combined risk factors > 2 and that came in agreement with Esref and colleagues and Yen-Nan and colleagues [10, 17].
There was strong correlation between NLR and NIHSS score, and the results indicate that a higher NLR is associated with stroke severity on admission and that came in agreement with Yen-Nan and colleagues and Sungwook and colleagues [17, 18].
On MRS done 3 months from acute ischemic stroke onset, NLR was associated with unfavorable outcome (MRS ≥ 3), which means that NLR is a predictor of post stroke disability and that came in agreement with Jin-Hyung and colleagues and Xue and colleagues [15, 19].
NLR was a high valid prognostic marker in predicting post stroke disability (MRS ≥ 3), after 3 months from stroke onset. The optimal cutoff value of NLR for prediction of primary unfavorable outcome was 2.05 with a sensitivity of 90% and a specificity of 96% (area under the curve 0.991, 95% CI 0.063–0.390) and that came in agreement with Serhat and colleagues [20].
Patients had significantly higher mean values of VWF: Ag ( p value, 0.001) than the control ones suggesting an evidence of increased acute endothelial activation in this patient population, and the association between VWF and acute ischemic stroke can be ascribed to the endothelial damage associated with cerebral infarcts or to the ischemia-related release of VWF from infarct tissues, and that came in the agreement of Tobin and colleagues and Menih and colleagues [21, 22].
There was significantly positive correlation between age and VWF: Ag in acute ischemic stroke patients and that came in agreement with Menih and colleagues [22].
There were significantly higher mean levels of VWF: Ag in patients with hypertension (p value 0.049), hypercholesterolemia (p value 0.001), overweight and obese (p value 0.003), combined risk factor > 2 (p value 0.034), and carotid artery stenosis (p value 0.034) and that came in agreement with Tobin and colleagues and Sonneveld and colleagues [21, 23]. However, van Loon and colleagues’ [24] study found no statistical significance between VWF: Ag levels and carotid artery stenosis. Also, there was significantly higher mean levels of VWF:Ag in patients with non-O-blood group (p value 0.052) than those of blood group-O- and that came in agreement with Menih and colleagues [22]. Patients with history of atrial fibrillation (p value 0.002) did not have significantly higher mean levels of VWF: Ag, and that came in agreement with Tobin and colleagues [21].
Patients with higher mean levels of VWF: Ag had significantly more prevalence of EFT ≥ 5 (p value 0.01), which means that VWF participates in the process of atherogenesis. Also, those with NLR ≥ 2 were having higher plasma levels of VWF:Ag than those with NLR < 2, and the explanation is that VWF levels increase during inflammation, and VWF facilitates neutrophil extravasation at sites of inflammation by destabilization of the endothelial barrier through platelet recruitment via their GlycoProtein Ib (GPIb) receptor.
There was no statistical significance between stroke severity on admission (NIHSS) and VWF: Ag levels and that came in the agreement of van Loon and colleagues [24]. However, that did not agree with Menih and colleagues [22] who found that high levels of VWF were associated with greater severity of stroke. The difference in results can be explained by fewer number of patients group in this study and difference in clinical presentations of acute ischemic strokes between the two studies.
Also, there was no statistical significance between post ischemic stroke disability and initial VWF: Ag plasma levels on MRS done 3 months after ischemic stroke onset and that came in agreement with Tobin and colleagues [21] but that did not come in agreement with Menih and colleagues [22]and Sonneveld and colleagues [23]who reported that high VWF: Ag levels may be associated with unfavorable functional outcome, as determined by the Modified Rankin Scale score. The difference in results can be explained by fewer number of patients group in this study and difference in clinical presentations of acute ischemic strokes between the two studies.
On binary logistic regression analysis for relevant risk factors in acute ischemic stroke patients, VWF: Ag and NLR were significant risk factors in acute ischemic stroke patients after adjustment of NLR, BMI (overweight and obese), hypercholesterolemia, carotid artery stenosis, and EFT≥ 5. In addition, VWF:Ag had higher risk in development of stroke than NLR ≥ 2 (95% CI 1.08, 1.97, and 0.095, 0.39 relatively) and that came in agreement with Sonneveld and colleagues [23].