In this study, we compared the serum level of CysC between ischemic stroke patients and healthy individuals, and we observed that CysC level was higher in patients within the first week of stroke onset than in control subjects. These findings interpreted in the context that CysC as an inhibitor of cysteine protease and high level of CysC affects the process of vascular remodeling by breaking the balance of proteolytic and anti-proteolytic activities. Therefore, CysC acts as a good biomarker for acute ischemic stroke. Going with our result, Xu and colleagues  noticed that elevated CysC levels were strongly associated with stroke. Yang and colleagues  have similar results and hypothesized that Cyst C plays an important role in the pathogenesis of atherosclerosis.
We should address that our study is limited by the small sample size which makes sensitivity 66% and specificity 100%.
In the present study, we found that there is no relation between the size of infarction and level of CysC, and we explain that serum levels of CysC were not affected by the size of infarction. First, because of the small number of participants with total MCA and combined MCA PCA territory infarction in comparison to patients with lacunar and branch MCA infarction. Second, that size of actual infarction may be smaller in brain image, and it appears large due to the presence of penumbra and vesogenic edema. On the other hand, Xiao and colleagues found that larger cerebral infarction size is associated with higher serum CysC. Therefore, CysC may be a predictor for the severity of ischemia and cell damage .
In the current study, a positive correlation was found between CysC level and NIHSS scores with statistical significance, so we concluded that CysC is a prognostic tool for stroke severity as the higher the CysC level, the severer the stroke. Zhiqiang and colleagues  show a positive correlation between CysC and NIHSS. While Zeng and colleagues  observed that correlation between CysC levels and NIHSS was not significant, that was conversely, to our results due to our selection criteria as our patients were in the first week of stroke.
As regards CysC predictive value, in the present study, increased IMT had a higher level of CysC with positive statistical significance. Matching with our result, Zhu and colleagues  noticed that CysC was strongly associated with carotid thickening and plaque. Moreover, Kaneko and colleagues  noticed that CysC is strongly and independently associated with arterial wall elasticity, which reflects the degree of subclinical atherosclerosis. On the contrary, Bui and colleagues  found no association between CysC with internal and common carotid IMT and such differences are due to their participants that were four different self-reported ethnic groups (white, African American, Hispanic, and Chinese).
In our study, when we compared the level of CysC between patients with extracranial, transcranial, and combined stenosis, we noticed that the highest level of CysC present in patients with extracranial stenosis with statistical significance that can be explained by that CysC contributes to the process of carotid atherosclerosis. Extracranial arteries are elastic arteries while intracranial arteries are muscle arteries, and atherosclerosis and vascular calcification occur in extracranial vessels while oxidative stress which induces endothelial dysfunction occurs in intracranial vessels. Moreover, patients with stenosis > 50% had higher levels of CysC compared to patients with stenosis < 50% with positive statistical significance. Extracranial stenosis > 50% had the highest level of CysC with positive statistical significance. Xu and colleagues  noticed that serum CysC was highly associated with large cerebral artery stenosis but not the location of large cerebral artery stenosis whether extracranial or intracranial. Going with our result, Umemura and colleagues  suggested that higher levels of CysC were independently associated with symptomatic extracranial ICA stenosis, but not with intracranial ICA/MCA stenosis in patients with non-cardioembolic stroke.
Peliseket and colleagues  also suggested that an imbalance between cysteine proteinase and CysC could impact changes in vascular structure and stenotic lesions. While Huang and colleagues  observed serum CysC is high in stroke patients but were not correlated with the presence of intracranial arterial stenosis.
In the present study, patients’ age and gender had no correlation with CysC level, and our finding implies that CysC was included in the process of carotid atherosclerosis via chronic inflammation and not related to demographic risk factors. Matching with our result, Yang and colleagues  observed no statistical significance between CysC and age or gender of stroke patients. Although Kobayashi and colleagues  observed a higher level of CysC in males.
In the current study, no significant correlation was found between CysC level and hypertension, diabetes, or smoking. So CysC is strongly and independently associated with arterial wall atherosclerosis. Going with our finding, Xiao and colleagues  and Huang and colleagues  found that serum CysC concentrations in stroke patients were not correlated with hypertension or diabetes. On the other hand, Yang and colleagues  observed a significant association between CysC level and hypertension and between CysC and diabetes. Kobayashi and colleagues  also noticed statistical significance between CysC level and hypertension, DM, and smoking, taking into consideration that there were few participants with severe kidney disease in these studies.
In our study, no statistical significance was found in comparing cystatin c level and lipid profile. Matching with our study result, Xiao and colleagues  and Huang and colleagues  found that CysC levels were not correlated with serum total cholesterol, high-density lipoprotein, and low-density lipoprotein levels. While on the contrary, Xu and colleagues  observed a significant correlation with serum CysC levels and serum triglycerides and cholesterol.
In the present study, no statistical significance was found between CysC level and electrolyte. Going with our finding, Gharaibeh and colleagues  found that serum electrolyte levels did not show any significant changes in cases compared to controls.