| In recent years, growing evidence supported that, cerebrovascular disease is becoming as the first reason of disability and death in our country.Epidemiological survey revealed that there are 1.5 to 2 million new cases of stroke in each year nationwide and there are nearly 7 million patients with cerebrovascular disease in which about 80% to 85% are ischemic stroke in our country. Large artery atherosclerotic stenosis is one of the main reasons of ischemic stroke and the formation of the unstable atherosclerotic plaque is thought to be involved in the pathologic progress of atherosclerotic stroke. In recent years, researches have achieved great progresses in the study of development of the atherosclerosis and the inflammatory markers of the complications. Typically the serum biomarkers which affect the prognosis of atherosclerosis have drawn more attention of researches. Thus, we hope to discover new therapeutic targets and to explore an effective biomarker to predict the risk of developing vascular stenosis, plaque stability and determine the short-term prognosis of stroke which have significant meanings in the prevention and treatment of acute stroke.Serum tissue protease S (Cathepsin S, Cat S)/cystatin C (Cystatin C, Cys C) system are the most attracting biomarkers in the atherosclerosis prognosis. Researchers have demonstrated that pathophysiologic alterations such as lipid deposition, endothelium injury, cell migration, endometrial hyperplasia, inflammation infiltration, thrombosis, matrix remodeling and vascular calcification involved in the occurrence, development and outcomes of vascular disease. Cat S/Cys C system plays an important role in regulating the pathophysiolo-gic development mentioned above. Recent studies have shown that Cat S could regulate the vascular inflammatory immune response, perform the extracellular matrix degradation and remodeling, initiate the stability of atherosclerotic plaque rupture and participate the transferring of cellular lipids and formation of foam cells. Therefore, Cat S/Cys C system exert critical role in the development of the cardiovascular diseases such as the atherosclerosis, acute cardiac events, vascular restenosis and heart failure. The relationships between Cat S and vascular stenosis, plaque characterizations and outcomes of ischemic stroke are poorly understood.ObjectiveTo investigate the relationship between Cat S/Cys C and intracranial/extracranial artery stenosis and plaque characterization, and association between Cat S/Cys C and short-term outcomes of stroke.MethodsThis study is a prospective case-control study and recruited patients diagnosed as atherosclerotic stroke in the neurological department of our hospital from the October 2012 to December 2013.The subjects were divided as stable plaque and unstable group respectively, and then each group was divided as mild stenosis, moderate stenosis and severe stenosis subgroups according to the stenosis intensity, healthy patients were recruited as health control. All the patients were evaluated the neurological impairment by NIHSS scale at day 1 after stroke occurance. The bloods were collected and the Elisa and latex-enhanced immunoturbidimetric assay methods were used to detect the serum levels of Cat S and Cys C respectively, and all the patients were performed the carotid artery ultrasound and MRA at day 2 after stroke occurrence. The levels of Cat S and Cys C were reexamined at day14 after stroke occurrence. The neurological impairments were reevaluated at day 90 after discharged by the modified Rankin Scale. The bloods of the control group were draw in the medical center of our hospital, the serum levels of Cat S/Cys C, lipid levels and glucose were detected as the methods mentioned above, the general records and the past history were also collected. The SPSS 13.0 statistical analysis software were used for the statistical analysis.ResultsThis study recruited 336 patients with 208 male and 128 female respectively. The mean age of the patients were 55.60±12.35 years old. According to the plaque characterization and the degree of the vascular stenosis, there were 146 patients recruited in the stable plaque group(with 30 mild stenosis,75 moderate stenosis and 41 severe stenosis respectively) and 190 patients in the unstable plaque group(with 116 mild stenosis,52 moderate stenosis and 22 severe stenosis respectively). There were 114 patients recruited in the control group, with the 58 males and 56 females respectively. The mean age of the control group were 50.02±10.32 years old.The levels of Cat S and ratio of Cat S/Cys C of the stroke group were significantly higher in stroke patients compared to the health controls, the mean of Cat S and ratios of Cat S/Cys C were (63.07+20.81)pg/ml/(50.49±10.54)pg/ml and (78.83±6.88)/(47.18±3.32) in patients and controls respectively. The levels of Cys C (0.80±0.11)mg/L of the stroke group were significantly lower than the health control (1.07±0.83)mg/LThe levels of Cat S and ratio of Cat S/Cys C of the unstable plaque group were significantly higher than the stable control group, the mean of Cats and ratios of Cat S/Cys C were (75.34±15.45)pg/ml/(60.12±18.53)pg/ml and (103.68±2.52)/ (64.64±9.24) respectively. The levels of Cys C (0.73±0.62)mg/L of the unstable plaque group were significantly lower than the stable plaque group (0.93±0.53)mg/L. In subgroups (mild stenosis, moderate stenosis and severe stenosis) analysis, the levels of Cat S, Cys C and ratios of Cat S/Cys C has significant difference (P<0.05), with the tendency that the levels of Cat S and ratios of Cat S/Cys C were positively and Cys C were negatively correlated with the vascular stenosis severity.The multiple regression analysis results showed that the serum level of Cat S were correlated with the short-term outcomes of the acute stroke. The higher levels of Cat S predict the poorer outcomes of stroke. Serum levels of Cat S and Cat S/Cys C were positively correlated with the occurrence of the ischemic stroke, with the OR value of Cat S were 3.733, the OR value of Cat S/Cys C were 5.096. Serum levels of Cys C were negatively correlated with the occurrence of the ischemic stroke.Conclusions1. The stroke patient serum levels of Cat S and raito of Cat S/Cys C were significantly higher and serum levels of the Cys C were significantly lower than the health controls.2. The level of Cat S was positively correlated with the vascular stenosis severtity and plaque activity in the stroke patients.3. The level of Cys C and raito of Cat S/Cys C were positively correlated with the risk of the ischemic stroke and the short-term mRS score, while they could predict the occurrence of the ischemic stroke and the short-term outcomes of the acute stroke. |
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