2.1 Study design and subjects: The present study was performed in Stroke Center of First Hospital Affiliated to Soochow University, and included 329 patients diagnosed with ischemic stroke who were admitted to our hospital between October 2015 to February 2018. The patients who underwent admission and finished MR-based imaging were included. The participants were divided into four groups: the control group (patients with neither hypertension nor HHcy), the isolated hypertension group, the isolated HHcy group and the H-type hypertension group. At least 2 trained neurologists from our stroke center evaluated the clinical features and diagnostic test results. All data were analyzed anonymously. Ethical approval for this study was obtained from the ethics committees of the First Hospital Affiliated to Soochow University and informed consent was obtained from all of our participants
2.2 Clinical information and indexes determination：Clinical variables of interest included age (calculated according to the ID birth date), gender, education level, marital status were collected. Lifestyle factors including smoking and alcohol consumption, past medical history, family history, disease history of hypertension history, diabetes history, stroke history, hyperlipidemia history and coronary heart disease history were obtained. Hypertension was defined as the presence any of the following: systolic blood pressure ≥ 140 mmHg, or diastolic pressure ≥ 90 mmHg for twice in quiet conditions or having self-reported history of hypertension. Diabetes mellitus was defined as the presence any of the following: fasting serum glucose > 7.0 mmol/L or postprandial 2h plasma glucose > 11.1 mmol/L or having previous history of diabetes. Hyperlipidemia was defined as having elevated level of one of triglyceride, total cholesterol or low density lipoprotein. Venous blood samples from the participants were collected on an empty stomach the second day after admission. The serum Hcy level were measured within 24h of hospitalization using enzymatic cycling method. HHcy was defined as Hcy concentration ≥12.0 umol/L. Full neurological examination, brain CT or MRI scan and carotid ultrasonography were also recorded.
2.3 Brain MRI acquisition and Analysis: The MR examination was performed within 48 hours after admission and sequences included T1-weighted, T2-weighted, fluid-attenuated inversion recovery (FLAIR), axial diffusion-weighted imaging (DWI), and TOF-MRA sequences. MR was rated for the presence of lacunes, white matter hyperintensities, cerebral microbleeds, and perivascular spaces independently. Lacunes was defined as rounded or ovoid shaped lesions, >3- and <20-mm diameter on T1, T2 or FLAIR sequences in basal ganglia, the white matter or brainstem. We defined microbleeds as small (<5 mm), homogeneous, round foci of low signal intensity on gradient echo images in basal ganglia, white matter, cerebellum, brainstem or cortico-subcortical junction(10). EPVS was defined as small (<3 mm) round or linear hyperintensities in the basal ganglia or centrum semiovale on T2 images, and they were rated using a five-point ordinal scale12 as follows: 0=no EPVS, 1=1-10 EPVS, 2=11-20, EPVS, 3=21-40 EPVS, and 4=>40 EPVS. Three trained neurologists and 2 neuroradiologists, each of whom was blinded to clinical information rated all the available scans for the presence and severity of SVD features. Deep and periventricular WMH were both coded according to the Fazekas scale from 0 to 3(11).
Based on the recent described score(4), we count the presence of each SVD feature and rated the total burden of SVD on an ordinal scale from 0 to 4. The MR manifestation of WMHs graded 2-3 according to Fazekas grading was recorded as 1 point, presence of CMBs or lacunes was recorded 1 point respectively, PVS graded 2-4 (≧11) was counted 1 point (Table 1). The severity of total SVD burden score were divided into three categories: mild (0 or 1 point), moderate (2 points), severe (3 or 4 points)(3, 12).
2.4 Statistical analysis: Statistical analysis was performed with SPSS13.0 (SPSS, Inc., Chicago, IL, USA). Normally distributed variables were presented as the mean ± Standard Deviation (SD) and categorical data were presented as frequency or ratio. Kolmogorov–Smirnov was used for the test of normality of quantitative data. Levene’s test was used to test homogeneity of variance. T test or one-way ANOVA was performed to compare the distribution of quantitative variables. χ2 test was used to compare the distribution of classification index. To determine the independent factors related to CSVD, we performed one variable analysis and multiple logistic regression analysis by using a backward elimination method and set the probability at 0.10 for removal. The statistical significance level was set at p <0.05 in the present study.